title: Distinctive exercise-induced inflammatory response and exerkine induction in skeletal muscle of people with type 2 diabetes

status: Public on Jul 06 2022

city: Stockholm

first: Carolina

last: Nylén

address: Karolinska University Hospital

country: Sweden

institute: Karolinska Institutet

summary: Mechanistic insights into the molecular events by which exercise enhances the skeletal muscle phenotype are lacking, particularly in the context of type 2 diabetes. Here we unravel a fundamental role for exercise-responsive cytokines (exerkines) on skeletal muscle development and growth in individuals with normal glucose tolerance or type 2 diabetes. Acute exercise triggered an inflammatory response in skeletal muscle, concomitant with an infiltration of immune cells. These exercise effects were potentiated in type 2 diabetes. In response to contraction or hypoxia, cytokines were mainly produced by endothelial cells and macrophages. The chemokine CXCL12 was induced by hypoxia in endothelial cells, as well as by conditioned medium from contracted myotubes in macrophages. We found that CXCL12 was associated with skeletal muscle remodeling after exercise and differentiation of cultured muscle. Collectively, acute aerobic exercise mounts a non-canonical inflammatory response, with an atypical production of exerkines, which is potentiated in type 2 diabetes.

overall_design: Skeletal muscle biopsies were collected from normal glucose tolerant (NGT) and type 2 diabetic (T2D) middle age men, before (rest), just after (post) and 3-hours after (recovery) a 30-minute bout of cycling, at an intensity of 85% of measured maximal heart rate.

first: Juleen

last: Zierath

first: Anna

last: Krook

first: Nicolas

last: Pillon


title: A single-cell transcriptomic analysis of endometriosis

status: Public on Oct 11 2022

city: Los Angeles

first: Marcos

last: Fonseca

state: CA

address: 8000 Beverly Boulevard

department: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology

country: USA

institute: Cedars-Sinai Medical Center

type: Expression profiling by high throughput sequencing

summary: We profiled transcriptomes of >370,000 individual cells from endometriomas (n=8), endometriosis (n=28), eutopic endometrium (n=10), unaffected ovary (n=4) and endometriosis-free peritoneum (n=4) to create a cellular atlas of endometrial-type epithelial cells, stromal cells, and microenvironmental cell populations across tissue sites.

overall_design: Single cells are captured and barcoded using the 10X Chromium platform (10X Genomics). scRNA-seq libraries were prepared following the instructions from Chromium Single Cell 3' Reagent Kits User Guide (v2 or v3). Briefly, Gel Bead-In EMulsions (GEMs) are generated using single cell preparations. After GEM-RT and cleanup, the cDNA from barcoded single cell RNAs were amplified before quantification using Agilent Bioanalyzer High Sensitivity DNA chips. The single cell 3' gene expression libraries were constructed and cDNA corresponding to an insertion size of around 350 bp selected. Libraries were quantified using Agilent Bioanalyzer High Sensitivity DNA chips and pooled together to get similar numbers of reads from each single cell before sequencing on the NovaSeq S4 (by Fulgent Genomics or Novogene).

first: Kate

last: Lawrenson

middle: A


title: Genetic mapping of multiple metabolic traits identifies novel genes for adiposity, lipids and insulin secretory capacity in outbred rats II

status: Public on Aug 15 2022

city: London

first: Thu

middle: Hong

last: Le

address: Gower Street

country: United Kingdom

institute: UCL

summary: RNA-Seq was used in an attempt to identify candidate genes regulating metabolic and physiological traits

overall_design: Physiological mapping identified physiological QTLs (pQTLs) affecting metabolic and physiological traits. Genes with cis-eQTLs mapped within each pQTL may may drive the physiological traits in a causal manner; and was assessed by mediation analysis.

middle: H

first: Leah

middle: C

last: Solberg Wood


title: Gene expression profile at single cell level of Basal Cells (BCs) from nasal scrapings of patients with and without cystic fibrosis

status: Public on Jun 30 2022

city: Stanford

first: Carlos

last: Milla

address: 770 Welch Road

department: Pediatrics - Pulmonary Medicine

institute: Stanford University

summary: Respiratory epithelium interact with our microbiome as well as environmental bacteria, and are critical in maintaining homeostasis in face of disruption such as injury or infection. Here we investigate the impact of a filamentous bacteriophage on responses of these cells to bacterial stimulus.

overall_design: Single-cell suspensions of basal cell culture were prepared by lifting adherent cells using trypsin digestion. Dead cells were removed using the MACS Dead Cell Removal kit (Miltenyi Biotech). Cells were then washed and counted as per manufacturer’s instructions and libraries were prepared using the 10X NEXT GEM 3’ Gene Expression Library scRNA Seq v3.1 reagents and workflow (10x Genomics). Library concentration and quality was confirmed by BioAnalyzer. Libraries were sequenced on the HiSeq PE150 platform.

middle: E

first: Elizabeth

middle: B

last: Burgener

first: Medeea

last: Popescu

first: Naomi

middle: L

last: Haddock


title: Autocrine Sfrp1 inhibits fibroblast invasion during transition to injury induced myofibroblasts - daily profiling of mouse lungs after Bleomycin injury

status: Public on Oct 12 2022

city: Biberach

first: Meshal

last: Ansari

address: Birkendorfer Straße 65

country: Germany

institute: Boehringer Ingelheim

summary: Fibroblast to myofibroblast conversion is a major driver of tissue remodeling in organ fibrosis. Here, we combined spatial transcriptomics, longitudinal single-cell RNA-seq and genetic lineage tracing to study fibroblast fates during mouse lung regeneration. We discovered a transitional fibroblast state characterized by high Sfrp1 expression, derived from both Tcf21-Cre lineage positive and negative cells. Sfrp1+ cells appeared early after injury in peribronchiolar, adventitial and alveolar locations and preceded the emergence of myofibroblasts. We identified lineage specific paracrine signals and inferred converging transcriptional trajectories towards Sfrp1+ transitional fibroblasts and Cthrc1+ myofibroblasts. Tgfβ1 downregulated Sfrp1 in non-invasive transitional cells and induced their switch to an invasive Cthrc1+ myofibroblast identity. Our study reveals the convergence of spatially and transcriptionally distinct fibroblast lineages into transcriptionally uniform myofibroblasts and identifies Sfrp1 as an autocrine inhibitor of fibroblast invasion during early stages of fibrogenesis.

overall_design: Single-cell transcriptomics experiment after bleomycin treatment

first: Christoph

last: Mayr

first: Arunima

last: Sengupta

first: Gerald

last: Burgstaller

first: Fabian

last: Theis

first: Herbert

last: Schiller


title: Methylation array of shNC, shUHRF1, shDNMT1, shDNMT3B THP-1 cells before and after PMA treatment

status: Public on Jun 24 2022

city: Seoul

first: Junyoung

last: Park

address: 84, Heukseok-ro

department: Department of Life Science

country: South Korea

institute: Chung-Ang University

type: Methylation profiling by genome tiling array

summary:
This methylation array was conducted to find out changes in genome-wide methylation pattern in THP-1 cells upon differentiation.
Also, we tried to figure out the effects of knockdown of UHRF1, DNMT1 and DNMT3B in THP-1 cells in regulating genome-wide DNA methylation.

overall_design: Control (shNC), UHRF1 knockdown (shUHRF1), DNMT1 knockdown (shDNMT1), DNMT3B knockdown (shDNMT3B) samples are analyzed before and after PMA treatment (No replicates)

first: Sang-Beom

last: Seo


title: Gene expression profile at single cell level of matched primary tumor and metastatic cells of breast cancer patient-derived xenograft models

city: San Francisco

first: Juliane

last: Winkler

address: 513 Parnassus Avenue

department: Department of Cell and Tissue Biology

institute: University of California, San Francisco

summary: We profiled the tumor heterogeneity of individual primary tumor and matched metastatic cells of breast cancer using a set of patient derived xenograft models with different metastatic potentials. This data set gives insights into the transcriptional tumor heterogeneity, the transcriptional differences between primary tumor and matched metastatic cells and how these are changing in regard to varying metastatic phenotypes.

overall_design: Live human tumor cells from breast primary tumor and matched metastatic lung tissues of patient-derived xenograft models were isolated using Fluorescence-activated cell sorting (FACS) based on the human specific CD298 antibody into 384 well plates and performed single cell library prep using Smart-Seq2 protocol.

first: Angela

last: Pisco

first: Spyros

last: Darmanis

first: Andrei

last: Goga


title: RNAseq on APAP mice flow sorted macrophages at 72h

status: Public on May 31 2022

city: Kansas City

first: David

middle: S

last: Umbaugh

email: dumbaug@gmail.com, hjaeschke@kumc.edu

state: KS

address: 3901 Rainbow Blvd

institute: University of Kansas Medical Center

summary: RNAseq of flow sorted macrophages 72h after APAP. Cxcr4 expression induced on subpopulation of macrophages after APAP.

overall_design: mRNA expression profiles of flow sorted macrophages in APAP at 72h. APAP was administered i.p at 300 mg/kg.

first: Nga

middle: T

last: Nguyen

first: Hartmut

last: Jaeschke


title: Bulk RNAseq of AB1-HA murine mesothelioma tumors from complete responders and partial responders to cyclophosphamide chemotherapy

status: Public on Aug 18 2022

city: Nedlands

first: Caitlin

middle: M

last: Tilsed

state: WA

address: 6 Verdun St

country: Australia

institute: NCARD,UWA

summary: Purpose: To compare the gene expression profiles of tumors from complete responders and partial responders to cyclophosphamide chemotherapy. AB1-HA murine mesothelioma tumors were excised one day prior to cyclophosphamide or three or seven days post cyclophosphamide.

overall_design: BALB/c mice bearing bilateral AB1-HA murine mesothelioma were treated 200 mg/kg cyclophosphamide. One tumor was surgically excised pre-treatment (one day prior to cyclophosphamide, day-1) or post-treatment (three or seven days after cyclophosphamide, day+3 or day+7) and RNAseq performed. The remaining tumor was used as a readout of response. For pre-treatment samples n=13 complete responders and n=13 partial responders. For post-treatment samples, n=10 complete responders and n=10 partial responders.

first: W

middle: J

last: Lesterhuis


title: circRNA and lncRNA transcriptome of cancer tissues, adjacent normal tissues and plasma exosomes of patients with intrahepatic cholangiocarcinoma

status: Public on Jun 01 2022

city: Beijing

first: Xuezhu

last: WANG

address: No.1 Shuaifuyuan Wangfujing Dongcheng District

country: China

institute: Peking Union Medical College Hospital

type: Non-coding RNA profiling by high throughput sequencing

summary: Intrahepatic cholangiocarcinoma (ICC) is a liver tumor featured by challenges of non-invasive early diagnosis and a higher prevalence rate in Asian countries. These characteristics necessitate the development of liquid biopsy and immunotherapy methods to improve the prognosis of patients with ICC. Herein, we conducted a pilot study on the transcriptome of tumor tissues, adjacent normal tissues, and plasma exosomes of Asian patients with ICC from northern and southern China. We identified a subgroup of immunogenic Asian ICC, which is different from Caucasian ICC and is characterized by T cell exhaustion and neutrophil extracellular traps. The levels of circ-PTPN22 (hsa_circ_0110529) and circ-ADAMTS6 (hsa_circ_0072688), potential circRNA biomarkers, were elevated in the ICC tumor tissues and plasma exosomes of this subgroup than in the other subgroups and normal controls. These circRNAs were derived from post-transcriptional backsplicing of PTPN22 and ADAMTS6 that were expressed in T cells and endothelial cells, respectively, in the ICC microenvironment. Our results revealed a subgroup of Asian ICC characterized by T cell exhaustion and neutrophil extracellular traps and marked by elevated levels of circ-PTPN22 and circ-ADAMTS6 in tumor tissues and plasma exosomes. This subgroup is potentially detectable by plasma exosomal circRNAs and treatable with immune checkpoint blockade.

overall_design: circRNA and lncRNA transcriptome of Homo sapiens: cancer tissues, adjacent normal tissues and plasma exosomes of patient with intrahepatic cholangiocarcinoma

last: Wang

first: Yongchang

last: Zheng

first: Haifeng

last: Xu


title: Epigenomic and transcriptomic analyses define core cell types, genes and targetable mechanisms for kidney disease

status: Public on Jun 16 2022

city: Philadelphia

first: Hongbo

last: Liu

state: PA

address: 3400 Civic Center Blvd

institute: University of Pennsylvania

type: Genome binding/occupancy profiling by high throughput sequencing

summary: More than 800 million people suffer from kidney disease, yet the mechanism of kidney dysfunction is poorly understood. Here we comprehensively characterize genetic associations for kidney function (n = 1,508,659 individuals), DNA methylation (n = 443 individuals) and gene expression (n = 686 individuals). We identify 878 (126 novel) kidney function associated GWAS loci and prioritize target genes for 87% of these loci using a multi-stage prioritization strategy. Heritability analysis reveal that methylation variation explains a larger fraction of GWAS heritability than gene expression. Integration of GWAS and single cell open chromatin (n = 57,229 cells) highlights the key role of proximal tubules and metabolism in kidney function regulation. Further, the causal role of SLC47A1 in kidney disease is defined in mice with genetic loss of Slc47a1 and in human individuals carrying loss-of-function variants. Our findings emphasize the key role of bulk and single-cell epigenomic information in translating genome-wide association studies into identifying causal genes, cellular origins and mechanisms of complex traits.

overall_design: 10x snATAC-seq for 4 human kidney samples. The processed data was based on six samples (including two samples from our previous dataset: GSE172008).

first: Ziyuan

last: Ma

first: Katalin

last: Susztak


title: Cell-free DNA 5-hydroxymethylcytosine as a marker for common cancer detection

status: Public on Sep 23 2022

city: Houston

first: Zejuan

last: Li

state: Texas

address: 6565 Fannin St, MC227

department: Department of Pathology and Genomic Medicine

institute: Houston Methodist Hospital

type: Methylation profiling by high throughput sequencing

summary: We used a highly sensitive nano-5hmC-Seal method and profiled the genome-wide distribution of 5-hydroxymethylcytosine (5hmC) in plasma cell-free DNA (cfDNA) from 384 patients with bladder, breast, colorectal, kidney, lung, or prostate cancer and 221 controls. We used machine learning and developed plasma cfDNA 5hmC signatures that are highly sensitive for cancer detection and cancer origin determination. We also identified genes and signaling pathways with aberrant DNA hydroxymethylation in six cancers.

overall_design: Analyze 5-hydroxymethyl cytosine (5hmC) genome-wide distribution in plasma cell-free DNA from bladder, breast, colorectal, kidney, lung, and prostate cancer patients in comparison to non-cancer controls

first: Jianming

last: Shao


title: Mycobacterium tuberculosis transcription factor, EmbR regulates expression of virulence factors that aid in ex vivo and in vivo survival

status: Public on Jul 01 2022

city: New Delhi

first: G Aneeshkumar

last: Arimbasseri

state: Delhi

address: Aruna Asaf Ali Marg

department: Molecular Genetics Laboratory

country: India

institute: National Institute of Immunology

summary: We report RNAseq analysis of Mycobacterium tuberculosis strain that lack transcription factor EmbR and the isogenic wild type. We identify the genes whose expression is altred by the mutation and show that genes associated with virulende are downregulated in EmbR KO cells.

overall_design: Comparison of the transcriptomes of wild type and EmbR KO Mmycobacterium tuberculosis H37Rv strains.

first: Suresh

last: Kumar

first: Mehak

last: Zahoor  Khan

first: Chen

last: Chongtham

first: G

first: Vinay

middle: K

last: Nandicoori


title: DNA methylation profile of myeloid/natural killer cell precursor acute leukemia (MNKPL)

status: Public on May 18 2022

city: Tokyo

first: Akira

last: Nishimura

address: 1-5-45 Yushima, Bunkyo-ku

department: Department of Pediatrics and Developmental Biology

country: Japan

institute: Tokyo Medical and Dental University

summary: Genome-wide DNA methylation profiling was conducted using DNA isolated from MNKPL. The Illumina EPIC methylation Beadchip array which covers more than 850,000 CpG loci was used. Samples include 7 cases.

overall_design: DNA methylation profiling was performed in 7 MNKPL using the Illumina EPIC methylation Beadchip array.

first: Kazuaki

last: Yokoyama

first: Takuya

last: Naruto

first: Chika

last: Yamagishi

first: Toshihiko

last: Imamura

first: Hiroto

last: Nakazono

first: Shunsuke

last: Kimura

first: Meiko

last: Ito

first: Maiko

last: Sagisaka

first: Yukie

last: Tanaka

first: Jinhua

last: Piao

first: Masakatsu

last: Yanagimachi

first: Takeshi

last: Isoda

first: Akinori

last: Kanai

first: Hirotaka

last: Matsui

first: Naoko

last: Higuchi

first: Akiko

last: Takada

first: Haruna

last: Okuno

first: Shoji

last: Saito

first: Shuhei

last: Karakawa

first: Shogo

last: Kobayashi

first: Daisuke

last: Hasegawa

first: Hiroyuki

last: Fujisaki

first: Daiichiro

first: Kazutoshi

last: Koike

first: Takashi

first: Shinya

last: Rai

first: Katsutsugu

last: Umeda

first: Hideki

last: Sano

first: Yujin

last: Sekinaka

first: Atsushi

last: Ogawa

first: Akitoshi

last: Kinoshita

first: Norio

last: Shiba

first: Mizuka

last: Miki

first: Fumihiko

last: Nakayama

first: Yozo

last: Nakazawa

last: Taga

first: Tomohiko

last: Taki

first: Souichi

last: Adachi

last: Manabe

first: Katsuyoshi

last: Koh

first: Yasushi

last: Ishida

first: Junko

last: Takita

last: Ishikawa

first: Hiroaki

last: Goto

first: Tomohiro


title: Comprehensive genomic analysis of myeloid/natural killer cell precursor acute leukemia (MNKPL)

first: Akira

last: Nishimura

summary: Whole exome sequencing and whole genome sequencing were performed using DNA isolated from MNKPL to identify genomic landscape. To investigate expression profiles of MNKPL, RNA sequencing (RNA-seq) was performed using RNA isolated from MNKPL. To clarify the origin and heterogeneity of MNKPL, single cell RNA-seq was conducted using leukemia cells of MNKPL and bone marrow mononuclear cells and CD34 positive bone marrow cells of a healthy donor.

overall_design: WES was performed using 18 samples in 13 cases (6 tumor/germline pairs, 6 tumor only sample). Whole genome sequencing was conducted in 6 cases. RNA-seq was performed in 6 cases. Single cell RNA-seq was performed in 2 MNKPL cases and 1 healthy donor.

first: Kazuaki

last: Yokoyama

first: Takuya

last: Naruto

first: Chika

last: Yamagishi

first: Toshihiko

last: Imamura

first: Hiroto

last: Nakazono

first: Shunsuke

last: Kimura

first: Meiko

last: Ito

first: Maiko

last: Sagisaka

first: Yukie

last: Tanaka

first: Jinhua

last: Piao

first: Masakatsu

last: Yanagimachi

first: Takeshi

last: Isoda

first: Akinori

last: Kanai

first: Hirotaka

last: Matsui

first: Naoko

last: Higuchi

first: Akiko

last: Takada

first: Haruna

last: Okuno

first: Shoji

last: Saito

first: Shuhei

last: Karakawa

first: Shogo

last: Kobayashi

first: Daisuke

last: Hasegawa

first: Hiroyuki

last: Fujisaki

first: Daiichiro

first: Kazutoshi

last: Koike

first: Takashi

first: Shinya

last: Rai

last: Umeda

last: Sano


title: Deep single-cell transcriptome analysis reveals transitional cancer cell state in the pancreatic cancer tumor microenvironment associated with poor prognosis

status: Public on May 01 2022

city: Daejeon

first: Jong-Eun

last: Park

address: 291, Daehak-ro, Yuseong-gu

institute: Korea Advanced Institute of Science and Technology

summary: Single cell transcriptome analysis of non-immune cell population in human pancreatic cancer tumor microenvironment

overall_design: Integrative analysis of single-cell transcriptome of non-immune cell population from 17 pancreatic cancer tumor tissues

first: Galam

last: Leem

first: Seongryong

last: Kim


title: Global analysis of binding sites of U2AF1 and ZRSR2 reveals RNA elements required for mutually exclusive splicing by the U2- and U12-type spliceosome

status: Public on May 24 2022

first: Young-Soo

last: Kwon

address: Nungdongro 209, Gwangjingu

department: Department of Bioscience and Biotechnology

institute: Sejong University

summary: Eukaryotic nuclear introns have been dichotomously classified into common U2-type introns and rare U12-type introns. Because the highly conserved consensus sequences for the 5’ splice site and the branch point are found within all U12-type introns, weighted matrices for these motifs are used for prediction of U12-type introns. However, the U12-type consensus sequences per se are also recognized by the U2-type spliceosome. To better understand how distinct splicing systems recognize their authentic splice sites, we determined the binding sites of splicing factors, U2AF1 and ZRSR2, and found that ZRSR2 binding is mostly limited to U12-type introns. Our results reveal RNA elements contributing to selection of U2-type and U12-type splice sites in a mutually exclusive manner.

overall_design: CLIP-seq of endogenous U2AF1 by using anti-U2AF1-antibodies (Bethyl), anti-HA-antibody for HA3-tagged ZRSR2 and IgG controls.


title: Molecular and Functional Remodeling of the Superior and Inferior Sinoatrial Nodes in a Rat Model of Hypertrophic Cardiomyopathy

status: Public on May 17 2022

city: Chicago

first: Igor

last: Efimov

state: Illinois

address: 303 E Superior St

institute: Northwestern University

summary:
Objectives: This study aimed to determine the transcriptional basis of functional silencing of one of the two dominant pacemakers in failing rat hearts.
Background: Recently, our laboratory presented functional and molecular evidence for the presence of two competing sinoatrial node (SAN) pacemakers in the healthy human and rat hearts. Anatomically localized near the superior vena cava and inferior vena cava, the superior and inferior SANs (sSAN and iSAN), respectively, preferentially control fast and slow normal heart rates. However, only one dominant pacemaker, primarily sSAN, was functional in the failing rat heart with hypertrophic cardiomyopathy.
Methods: Ascending aortic constriction was performed on 1-week-old male Sprague-Dawley rat pups to induce left ventricular hypertrophy and heart failure. The dominant pacemaker was anatomically mapped in adult (8-12 weeks old) healthy and failing rat hearts using optical mapping in isolated right atrial tissue preparations. RNA sequencing was used to identify regional sSAN/iSAN gene expression differences between healthy and failing rat hearts.
Results: In all failing rat hearts optically mapped in this study (n=4), only the sSAN pacemaker was functional, while the iSAN was silent. Compared to healthy rat hearts, a total of 3,640 genes were downregulated and 4,518 genes were upregulated in failing rat hearts. The functional quiescence of the iSAN in these failing rat hearts may be explained by their downregulation of sodium, potassium, and calcium ion channels as well as their downregulation of certain structural genes, including ankyrin, titin, and myosin heavy chain. Moreover, the iSAN showed predominant downregulation of several key transcription factors such as TBX5, TBX3, SHOX2, and SMAD9.
Conclusions: Pressure-overload-induced heart failure resulted in significant downregulation of critical transcription factors, ion channels, and structural transcripts of the iSAN, which could explain the functional silencing of the iSAN in failing rat hearts.

overall_design: RNA-Seq of healthy and failing rat heart samples from inferior and superior sino-atrial nodes, left atria, right atria, and left ventricles.

first: Anna

last: Gams

first: Jaclyn

last: Brennan

first: Katherine

last: Goldrick

middle: R


title: Single cell RNA sequencing on the early hepatic transcriptomic landscape

status: Public on Apr 13 2022

first: David

last: Umbaugh

summary: Single cell RNA sequencing, spatial reconstruction of the liver lobule after acetaminophen (300 mg/kg)

overall_design: Hepatocytes were isolated from either control or APAP-treated mice (2h) and underwent 10x Chromium 3' single cell RNA sequencing

first: Hartmut

last: Jaeschke

first: Anup

last: Ramachandran


title: DiffBrainNet: A combined resource of differential networks and differential expression to analyze transcriptomic responses to glucocorticoids in 8 mouse brain regions.

status: Public on Apr 15 2022

city: Munich

first: Elisabeth

last: Binder

address: Kraepelinstr. 2-10

institute: Max Planck Institute of Psychiatry

summary: Activation of the stress-axis is an important component of the biology of stress-related psychiatric disorders. The main stress hormones of the mammalian body are glucocorticoids. Glucocorticoids bind to glucocorticoid receptors and act as transcription factors modulating the transcriptional landscape. Dexamethasone is a synthetic glucocorticoid that is used to activate the glucocorticoid receptors and thus mimic some aspects of the altered transcriptomic landscape that are associated with stress-related psychiatric disorders. We used intraperitoneal dexamethasone of C57Bl/6 mice and analyzed the transcriptional landscape of 8 brain regions: the prefrontal cortex, the amygdala, the paraventricular nucleus of the hypothalamus, the dorsal and ventral Cornu ammonis 1, the dorsal and ventral dentate gyrus and the cerebellar cortex. We implored differential expression in combination with differential network analysis to study the transcriptomic responses to dexamethasone in each brain region. We found that differential networks and differential expression explain distinct but complementary aspects of the responses to the stimulus and that network analysis can unravel underlying biological mechanisms that are hidden at the gene level. Using our dataset we could analyze the molecular connectivity of Tcf4, an important psychiatric risk gene, at the baseline and differential levels. We provide an analysis framework and a resource for the study of the transcriptional landscape of 8 mouse brain regions at baseline, dexamethasone-treated and differential levels, called DiffBrainNet (http://134.76.24.68/app/diffbrainnet), that can be used pinpoint molecular pathways important for the basic functioning and response to glucocorticoids in a brain-region specific manner.

overall_design: RNA sequencing with subsequent differential expression analysis an differential network analysis in 8 brain regions (PFC, PVN, AMY, vDG, dDG, vCA1, dCA1, CER) after dexamethasone treatment (IP, 10mg/kg, 4 hours) of adult male C57Bl/6 mice (15 controls and 15 dexamethasone treated).

first: Nathalie

last: Gerstner

first: Anthi

last: Krontira

first: Janine

last: Arloth

first: Cristiana

last: Cruceanu

first: Simone

last: Roeh

first: Mathias

middle: V

last: Schmidt


title: Effect of depletion of UHRF1, DNMT1, DNMT3B during differentiation

status: Public on Jun 25 2022

first: Junyoung

last: Park

summary: To investigate gene regulation by UHRF1, DNMT1, DNMT3B in THP-1 cells during differentiation, we established stable knockdown THP-1 cell lines.

overall_design: We then performed gene expression profiling analysis using data obtained from RNA-seq before and after PMA treatment.

first: Sangbeom

last: Seo


title: Genome-wide characterization of i-motifs and their potential roles in the stability and evolution of transposable elements in rice

city: Nanjing

first: Xing

last: Ma

address: No.1 Weigang, Nanjing, Jiangsu 210095, P. R. China

institute: Nanjing Agricultural University

summary: I-motifs (iMs) are non-canonical DNA secondary structures that fold from cytosine (C)-rich genomic DNA regions termed putative i-motif forming sequences (PiMFSs). The structure of iMs is stabilized by hemiprotonated C–C base pairs and their functions are now suspected in key cellular processes in human cells such as genome stability and regulation of gene transcription. In plants, their biological relevance is still largely unknown. Here, we characterized iMs in the rice genome by developing and applying a protocol hinging on an iMab antibody-based immunoprecipitation (IP) coupled with high throughput sequencing (seq), consequently termed iM-IP-seq. We found that PiMFSs had intrinsic subgenomic distributions, cis-regulatory functions and an intricate relationship with DNA methylation. We indeed found that the coordination of PiMFSs with DNA methylation may affect dynamics of transposable elements (TEs) among different cultivated Oryza subpopulations or during evolution of wild rice species. Collectively, our study provides first and unique insights into the biology of iMs in plants, with potential applications in plant biotechnology for improving important agronomic rice traits.

overall_design: Three biological replicates of iM-IP-seq in rice seedling

first: Yilong

last: Feng

first: Ying

last: Yang

first: Xin

last: Li

first: Yining

last: Shi

first: Shentong

last: Tao

first: Xuejiao

last: Cheng

first: Jian

last: Huang

first: Xiu-e

last: Wang

first: Caiyan

last: Chen

last: Monchaud

first: Wenli

last: Zhang


title: Gene expression profile in WBC of ADHD patients

status: Public on Jun 06 2022

city: Kaohsiung

first: Sung-Chou

state: Kaohsiung

address: No.386, Dazhong 1st Rd

department: Department of Medical Education and Research

country: Taiwan

institute: Kaohsiung Veterans General Hospital

summary:
In our previous study, we found that WBC miRNA may serve as ADHD prediction biomarkers. Therefore, we wonder whether WBC gene expression profile could also serve as ADHD biomarkers.
We enrolled ADHD and healthy control subjects, followed by collecting RNA samples from total WBC.

overall_design: We had the RNA samples prepared and examined microarray assays.

first: Liang-Jen


title: Modeling of myogenesis using human embryonic stem cells reveals myotonic dystrophy type 1 specific misregulated cellular processes

status: Public on Mar 31 2022

city: Brussels

first: Claudia

last: Spits

address: Laarbeeklaan 103

department: Research Group of Reproduction and Genetics

country: Belgium

institute: Vrije Universiteit Brussel

summary: We report the analysis of RNA sequencing results performed on human embryonic stem cells, carrying the myotonic dystrophy type 1 (DM1) mutation naturally, and their derived myoblasts and myotubes. The goal of the study was to reveal DM1-specific mechanisms during early myogenic development. After RNAseq analysis we found a subtle aberrant inflammation response in DM1 myoblasts possibly leading to an abnormal myotube formation thereafter. In addition an increased CpG methylation pattern upstream of the DM1 mutation was found and RNA missplicing events start to be abundantly present from the myotube stage on. We conclude that our in vitro model can recapitulate DM1-specific mechanisms and opens doors to a deeper understanding of the fundamental mechanisms of humen disease.

overall_design: RNA profile in three DM1 human embryonic stem cells and their derived myoblasts and myotubes and three non-DM1 cell lines were used as controls.

first: S

last: Franck

first: C

first: K

last: Sermon

first: E

last: Couvreu de Deckersberg


title: A Synthetic Lethality Screen Reveals ING5 as a Genetic Dependency of Catalytically Dead Set1A/COMPASS in Mouse Embryonic Stem Cells

status: Public on Mar 28 2022

first: Bercin

last: Cenik

state: IL

department: Biochemistry and Molecular Genetics

summary: Embryonic stem cells (ESCs) are defined by their ability to self-renew and the potential to differentiate into all tissues of the developing organism. We previously demonstrated that deleting the catalytic SET domain of the Set1A/COMPASS histone methyltransferase in mouse ESCs does not impair their viability or ability to self-renew, however, leads to defects in differentiation. The precise mechanisms by which Set1A executes these functions remain to be elucidated. In this study, we demonstrate that mice lacking the SET domain of Set1A are embryonic lethal at a stage that is unique from null alleles. To gain insight into Set1A function in regulating pluripotency, we conducted a CRISPR/Cas9-mediated dropout screen and identified the MOZ/MORF and HBO1 acetyltransferase complex member ING5 as a synthetic perturbation to Set1A. The loss of Ing5 in Set1AΔSET mESCs decreases the fitness of these cells; and the simultaneous loss of ING5 and in Set1AΔSET leads to upregulation of differentiation-associated genes. Taken together, our results point towards Set1A and ING5 as potential co-regulators of the self-renewal and differentiation status of ESCs.

overall_design: We performed RNA-seq and ChIP-seq experiments in mouse embryonic stem cells, embryoid bodies differentiated from mouse embryonic stem cells, and mouse embryos that were WT, SET1A mutants lacking the catalytic SET domain of the protein, and/or lacking the ING5 protein to investigate the role of SET1A and ING5 in stem cell self-renewal and differentiation.

first: Christie

last: Sze

first: Ali

last: Shilatifard


title: Expression data from patient female with acute promyelicytic leukemia

status: Public on Jun 03 2022

city: Guadalajara

first: Jennifer

last: Santana Hernández

state: Jalisco

address: Sierra Mojada 950, Independencia Oriente

department: Instituto de Genética Humana

country: Mexico

institute: Universidad de Guadalajara

summary:
The objective of the present study is to describe the gene expression of acute promyelocytic leukemia and PML/RARA oncoprotein, in a pediatric female patient, according to their clinical characteristics, immunophenotype and karyotype
We used microarrays to detail the clinic and evolution of leukemia with gene expression and identified biomarkers more importan found up or down regulated genes during this process.

overall_design: The study describes the unusual simultaneous presence of PML/RARA fusion gene bcr1, bcr2 and bcr3 transcripts, in a pediatric female patient diagnosed with APL, according to their clinical characteristics, immunophenotype, classical cytogenetic and prognosis. We included also, a functional implications analysis based on expression arrays.

first: Idalid

last: Cuero-Quezada

last: Santana-Hernández


title: Comprehensive transcriptome profile of AGS gastric cancer cells treated with flavonoid prunetin

status: Public on Mar 21 2022

city: Jinju

first: Preethi

last: Vetrivel

state: Singapore

address: Gajwa-dong

institute: Gyeongsang National University

summary: Gastric cancer is the common type of malignancy positioned at second in mortality rate causing burden worldwide with increasing treatment options. The application of transcriptomics technologies possesses the high efficiency of identifying key metabolic pathways and functional genes in cancer research.Prunetin (PRU) is an O-methylated flavonoid that belongs to the group of isoflavone executing beneficial activities. In the current study, a transcriptome profile on treated and untreated conditions of flavonoid prunetin was performed in order identify the differential expression of genes which eventually aids in preditcing candidate biomarkers.

overall_design: Identification of differentially expressed genes on treatment with prunetin in gastric cancer

first: Gon

last: Kim


title: RNAseq analysis of two PWS mouse model brains

status: Public on Mar 14 2022

city: Cardiff

first: Anthony

last: Isles

address: Hadyn Ellis Building

institute: Cardiff University

summary: We report the RNAseq nalysis of transcription in the brains of two mouse models for PWS. PWScr and and PWS-IC mice have overlapping and and distinct changes in gene expression and isoform usage. The increased number of changes seen in PWS-IC brain are enriched for genetic variants associated with psychotic illness.

overall_design: Examination of whole brain at P0 in PWScr mice and their wildtype littermates, and PWS-IC mice and their littermates

first: Simona

last: Zahova


title: Phenotypic plasticity underlies local invasion and distant metastasis in ovarian cancer

status: Public on Jan 06 2022

city: Rotterdam

first: Mathijs

last: Verhagen

address: Doctor Molewaterplein 40

country: Netherlands

institute: Erasmus Medical Center

summary: Phenotypic plasticity underlies invasion and distant metastasis in ovarian cancer

overall_design: CD44highEpCAMhigh and CD44highEpCAMlow RNAseq profiles of ovarian cancer cell lines OV90, CAOV3 and SKOV6

first: M

last: Teeuwssen

first: A

last: Sacchetti

first: H

last: van de Werken

first: R

last: Fodde


title: PSMD14 Stabilizes Estrogen Signaling and Facilitates Breast Cancer Progression via Deubiquitinating ERα

status: Public on Feb 23 2022

city: XinXiang

first: Yang

last: Xiao

institute: XinXiang Medical Universtiy

summary: NOT PROVIDED; REQUESTED

overall_design: Breast cancer cell mRNA samples were summarized in six samples, divided into two groups, siControl and siPSMD14

first: Xiao

last: Yang

first: Huijie

first: Jian

last: Zhu

first: Ting

last: Zhuang


title: V. cholerae transcriptome in MH, supplemented or not with glucose 0.4% or maltose 0.4%

status: Public on Feb 16 2022

city: Paris

first: Zeynep

last: Baharoglu

address: 28 Rue du Docteur Roux

department: Génomes et Génétique

country: France

institute: Institut Pasteur

summary: We study gene expression levels of V. cholerae N16961 WT and crp mutant strains/V. cholerae N16961 hapR+ corrected strain, ravAviA mutant and ravAviA overexpressing strains in exponential phase in MH, MH+maltose 0.4% and MH+glucose 0.4%

sample_organism: Vibrio cholerae O1 biovar El Tor str. N16961

overall_design: Bacterial cells were grown to OD 0.3 and RNAseq was performed.

first: Evelyne

last: Krin

first: André

last: Carvalho

first: Manon

last: Lang

first: Etienne

last: Kornobis

first: Elodie

last: Turc

first: Didier

last: Mazel


status: Public on Feb 28 2022

city: Changsha

first: Kaixuan

last: Li

state: Hunan

address: 87 Xiangya Road, Kaifu District

institute: Xiangya Hospital Central South University

summary: We established the ketamine-induced cystitis (KIC) models in female Sprague-Dawley rats. The bladder of the ketamine group and the control group were obtained to perform transcriptome analysis.

overall_design: The transcriptomic analysis of bladder tissue in a rat model of ketamine-induced bladder fibrosis. 3 KIC group rats bladder tissue VS 3 control group rats bladder tissue.

first: Kaixan

first: Haozhen

first: Zhao

last: Wang

first: Quan


title: Bulk RNA sequencing data of AB1-HA murine mesothelioma tumors from mice treated with tretinoin and immune checkpoint therapy

status: Public on Mar 17 2022

city: Crawley, Perth

first: Emma

last: de Jong

address: 35 Stirling Hwy

institute: University of Western Australia

summary: Bulk RNA sequencing data of AB1-HA murine mesothelioma tumors from mice treated with tretinoin, immune checkpoint therapy or the combination of tretinoin+immune checkpoint therapy.

overall_design: Mice bearing AB1-HA were treated with PBS (n=10), tretinoin (n=9), immune checkpoint therapy (anti-CTLA-4+ anti-PD-L1, n=10) or combination tretinoin+immune checkpoint therapy (n=10). 5 mg/kg tretinoin was dosed i.p for 5 doses beginning on day 4. Immune checkpoint therapy commenced on day 7. One tumor was surgically resected on day 9 and stored for RNAseq. For the combination treatment, the remaining tumour was monitored for treatment outcome; responders (R, blue n=6) or non-responders (NR, red, n=4).

first: Caitlin

last: Tilsed

first: Tom

last: Casey

first: Anthony

last: Bosco

first: Rachael

last: Zemek

first: Joanne

last: Salmons

first: Graeme

last: Wan

first: Michael

last: Millward

first: Anna

last: Nowak

first: Richard

last: Lake

first: W

last: Lesterhuis


title: RNA sequencing of hiPSC-derived endothelial cells via doxycycline-induced ETV2 transcription factor overexpression

city: Leuven

first: Yoke Chin

last: Chai

state: Leuven

address: Herestraat 49, ON5

department: Development & Regeneration

institute: KU Leuven

summary: Endothelial cells are known to express tissue-specific phenotypes to support the organ functionality due to the residing tissue microenvironment niche. The objective of this study is to compare the transcriptomic profiling of the generated endothelial cells (called iETV2-ECs) in neuro maintenance medium (NMM) with endothelial cells derived from primary human brain and other organs, as well as human induced pluripotent stem cells. The iETV2-ECs were generated from human induced pluripotent stem cells (hiPSC) that were genome engineered with a doxycycline-inducible overexpression cassette for the master regulator of endothelial differentiation (i.e. ETV2). The cells were treated with doxycycline for 8 days in the NMM supplemented with bFGF, FBS and endothelial cell growth supplements and subsequently maintained in NMM up to 21 days. Cells were harvested on day 8, 14 and 21 days for total RNA extraction, and their transcriptomic profiles were analyzed by bulk RNA sequencing technique. P  ublicly-available RNA sequencing datasets of different endothelial cell types were integrated into the iETV2-EC data set for differentially expressed genes analysis. The ultimate goal of this project is to develop vascularized 3D neural model to study human brain vascularization and disease modelling.

overall_design:
The goal of this study is to analyze the transcriptomic profiling of the generated endothelial cells (iETV2-Ecs) in neuro maintenance medium.
RNA profiles of endothelial cells at day 8, 14 and 21 days. Three independent samples for each time points (n=3)

first: Yoke

first: Stefaan

last: Verhulst

first: Leo

last: van Grunsven

first: Catherine

last: Verfaillie


title: SUMOylation inhibition overcomes dexamethasone resistance in multiple myeloma

status: Public on Dec 31 2021

city: Duarte

first: Hsun

middle: Teresa

last: Ku

address: 1500 E. Duarte Road

department: Translational Research and Cellular Therapeutics

institute: City of Hope

summary: SUMOylation, a posttranslational modification, regulates proteins by covalent attachment of small ubiquitin-like modifier (SUMO) proteins to a lysine (Lys) residue on target proteins. Here we use TAK-981, a selective SUMO-activating enzyme (SAE) inhibitor, to inhibit global SUMOylation in glucocorticoid sensitive and resistant multiple myeloma cell lines.

overall_design: Human multiple myeloma cell lines MM1.S (glucocorticoid sensitive) and MM1.R (glucocorticoid resistant) were treated with 0.1μM TAK-981, or 1μM Dexamethasone or combo (0.1μM TAK-981 and 1μM Dexamethasone) for 48 h in duplicate, total RNAs were extracted and sequenced.

first: Li

last: Du

first: Steven

last: Rosen


title: Human Obstructive and Non-obstructive Hypertrophic Cardiomyopathy Disease Mechanisms

status: Public on Jan 01 2022

city: Boston

first: Gayani

last: Perera

state: MA

address: 800 Washington Street

department: MCRI

institute: Tufts Medical Center

summary: To understand the interplay between cardiomyocyte and nonmyocyte cell types in human obstructive and non-obstructive hypertrophic cardiomyopathy, single nuclei RNA-sequencing was performed on 2 unused donor hearts, 1 obstructive HCM specimen, and 6 non-obstructive HCM specimens.

overall_design: Specimens were sampled for single nuclei transcriptomic sequencing. Sample 16 was generated and sequenced on its own NovaSeq S4 run. Samples 14-15 and 17-22 were generated and sequenced togheter on a separate NovaSeq S4 run.

first: Christina

last: Codden

last: Chin


title: Phenotypic Screening with Deep Learning Identifies HDAC6 Inhibitors as Cardioprotective Agents in Mouse Models of Dilated Cardiomyopathy

city: South San Francisco

first: Farshad

last: Farshidfar

address: 171 Oyster Point Blvd Ste 500

institute: Tenaya Therapeutics Inc.

summary: Dilated cardiomyopathy (DCM) is characterized by reduced cardiac output, as well as thinning and enlargement of left ventricular chambers. These characteristics eventually lead to heart failure. Current standards of care do not target the underlying molecular mechanisms associated with genetic forms of heart failure, driving a need to develop novel therapeutics for DCM. To identify candidate therapeutics, we developed an in vitro DCM model using induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) deficient in BCL2-associated athanogene 3 (BAG3). With these BAG3-deficient iPSC-CMs, we identified cardioprotective drugs with a phenotypic screen and deep learning. Using a library of 5500 bioactive compounds and siRNA validation, we identified that inhibiting histone deacetylase 6 (HDAC6) was cardioprotective at the sarcomere level. We translated this finding to a BAG3 cardiac-knockout (BAG3cKO) mouse model of DCM, showing that inhibiting HDAC6 with two isoform-selective inhibitors (tubastatin A and a novel inhibitor TYA-018) protected heart function. In BAG3cKO and BAG3 E455K mice, HDAC6 inhibitors improved left ventricular ejection fraction and reduced left ventricular diameter at diastole and systole. We also found that HDAC6 inhibitors protected the microtubule network from mechanical damage, increased autophagic flux, decreased apoptosis, and reduced inflammation in the heart. Our results demonstrate the power of combining iPSC-CMs with phenotypic screening and deep learning to accelerate target and drug discovery, and they support the development of novel therapies that address underlying mechanisms associated with heart disease.

overall_design: We conducted RNA-Seq analysis of coding genes in hearts harvested from the three arms (WT+Veh, BAG3cKO+Veh, and BAG3cKO+TYA-018)

first: Jin

last: Yang

first: Francis

last: Grafton

first: Ana

last: Budan

first: Sara

last: Ranjbarvaziri

first: Marie

last: Cho

first: Emma

last: Xu

first: Jaclyn

last: Ho

first: Mahnaz

last: Maddah

first: Kevin

last: Loewke

first: Julio

last: Medina

first: David

last: Sperandio

first: Snahel

last: Patel

first: Tim

last: Hoey

first: Mohammad

last: Mandegar


title: Molecular characterization of the effects of shift work and food consumption on cardiovascular disease in the rat

status: Public on Dec 22 2021

city: College Station

first: Jerome

last: Menet

address: Texas A&M University Biology Department 3258 TAMU College Station, TX 77843

department: Biology

institute: Texas A&M University

summary: Shift work misaligns the circadian clock and leads to an increased risk of cancer, cardiovascular diseases, and metabolic disorders. Furthermore, food consumed during the rest phase is a major contributor to this misalignment, as food access restricted to the endogenous active phase, at night, prevents against the adverse effects of shift work on obesity and diabetes in rats. In this study, we aimed to investigate the molecular mechanisms by which shift work and food consumption contribute to an increased risk of cardiovascular disorders. To this end, we used a model of shift work in rats, whereby animals are exposed to a 12:12 light:dark cycle and are forced to be active for eight-hours during their natural rest phase during the day, Monday to Friday for five consecutive weeks. Given the preventive effects of temporal restriction of food intake, a group of shift worker rats with food access restricted to the night was included in addition to controls and shift workers. To gain insight into the molecular underpinnings of shift-work associated cardiovascular pathologies, we performed RNA-Seq analysis and Picrosirius Red staining in rat hearts. Our results show that shift work in rats, regardless of the time of food consumption, have an increase in collagen deposition in the heart. In addition, the expression of many genes encoding key fibrotic pathways was found to be up-regulated in shift worker rats that had their food restricted to the active phase. Altogether, our results suggest that five weeks of shift work in rats is capable of inducing cardiovascular disease through an up-regulation of collagen deposition in the heart.

overall_design: mRNA sequencing on rat hearts under 3 different shiftwork paradigms at 6 timepoints in triplicate

first: Alexandra

last: Trott


title: Targeting MYC Transcription with Small Peptide Derived from KSHV Transactivator (RNA-Seq)

status: Public on Dec 01 2021

city: Sacramento

first: Clifford

middle: G.

last: Tepper

address: 4645 2nd Avenue, Room 2300A

department: Biochemistry and Molecular Medicine

institute: UC Davis School of Medicine

summary: Herpesviruses rely on host cell transcription and translation machineries for replication. Viral proteins thus function to redirect multiple cellular proteins for viral replication. In herpesvirus replicating cells, host cell gene transcription is frequently down-regulated because important transcriptional apparatuses are appropriated by viral transcription factors. Here we show that an evolutionally-shaped viral protein sequence is a great starting material for unique drug development to modulate cellular transcription. Cellular c-Myc protein (MYC) is overexpressed in over 70% of all types of cancer cells and therefore a very attractive target to control cancer cell growth. We identified a small functional peptide derived from the Kaposi's sarcoma-associated herpesvirus transactivator (K-Rta), which strongly attenuates MYC expression, reduces cell proliferation, and selectively kills cancer cells in both tissue culture and a xenograft tumor mouse model. Mechanistically, the peptide blocks promoter-enhancer interactions by preventing coactivator complex consisting of Nuclear receptor coactivator 2, p300, and SWI/SNF proteins from engaging the MYC promoter in leukemia cells. Target gene profiling with SLAM-seq suggests that the viral peptide attenuates MYC expression through a mechanism likely different from that of BET bromodomain inhibitors. Furthermore, fusing the 13 amino acids peptide with humanized anti-CD22 single chain armed the antibody drug with cell killing ability, and inhibited cell growth in soft agar. Our studies thus demonstrate the utility of the peptide sequence as a therapeutics module, which may be used to modulate MYC activity in a cell type-specific manner.

overall_design:
The goal of these studies was to utilize comprehensive transcriptomic profiling in order to determine the gene expression and pathway alterations mediated by treatment with a novel small functional peptide therapeutic derived from the Kaposi's sarcoma-associated herpesvirus (KSHV)-transactivator (K-Rta), which strongly attenuates MYC expression. This was performed in the context of the (TREx)BCBL-1, BC-1, and BC-3 cell line models, which are derived from KSHV-infected human primary effusion lymphomas (PEL) and contain latent KSHV genomes.  TREx-K-Rta BCBL-1, also referred to as (TREx)BCBL-1, is an engineered subline, which contains a Tetracycline/Doxycycline (Dox)-inducible Flagx3- and HAx3-tagged K-Rta expression cassette. Viral reactivation is then stimulated by inducing K-Rta expression in individual TREx-K-Rta BCBL-1 cultures by treatment with Dox for 24 hours. For this study, replicate cultures from each cell line were treated with either wild-type or mutant versions of the petide at a concentration of 24uM for 24hrs. Following treatment, the cells were then harvested for isolation of total RNA and followed by library preparation and next-generation sequencing (NGS).

UPDATE: [Feb 27, 2024] The raw data associated with GSM5284906 and GSM5284909 were corrected.

first: Yoshihiro

last: Izumiya

middle: G


title: A macrophage-mediated TNFa signaling axis within peripheral nerves is required for initiation of autoimmune peripheral neuropathy

status: Public on Nov 30 2021

city: Los Angeles

first: Maureen

last: Su

state: California

address: 615 Charles E Young Dr S

institute: UCLA

summary: Immune cells infiltrate peripheral nerves after injury and with autoimmunity, but their net effect is divergent. After injury, immune cells are reparative, while in autoimmune neuropathies (e.g., GBS and CIDP), immune cells are pro-inflammatory and promote autoimmune demyelination. An understanding of immune cell phenotypes that distinguish these conditions may therefore reveal new therapeutic targets for switching immune cells from an inflammatory to a reparative state. In an autoimmune neuropathy mouse model, we used single cell transcriptomic studies of sciatic nerves to discover a TNFα signaling axis induced by IFNγ. Macrophages were the main source of TNFα, and autocrine TNFα signaling upregulated multiple autoimmunity-associated genes (e.g., Clec4e; Marcksl1; Cxcl1; Cxcl10). TNFα signaling was absent in nerve macrophages after injury, suggesting that TNFα signaling defines autoimmunity-associated pro-inflammatory macrophages.  Finally, TNFα/TNFα signaling blockade ameliorated PNS autoimmunity development, which provides pre-clinical evidence that the TNFα axis may be effectively targeted to resolve inflammatory neuropathies.

overall_design: Examination of single-cell profiles of immune cells in NOD.AIRE GW/+ and wild-type sciatic nerves

middle: A

first: Yan

last: Wang

first: Lily

last: Guo

first: Xihui

last: Yin

first: Ethan

last: McCarthy

first: Mandy

middle: I

last: Cheng

first: Aline

last: Hoang

first: Ho-Chung

last: Chen

first: Anushi

middle: Y

first: Denise

last: Trout

first: Erin

first: Natalie

last: Yakobian

first: Willy

last: Hugo

first: James

middle: F

last: Howard Jr

first: Katherine

last: Sheu

first: Alexander

last: Hoffman

first: Melissa

last: Lechner


title: Genetic mapping of multiple metabolic traits identifies novel genes for adiposity, lipids and insulin secretory capacity in outbred rats

city: London

first: Thu

middle: Hong

last: Le

address: Gower Street

institute: UCL

summary: RNA-Seq was used in an attempt to identify candidate genes regulating metabolic and physiological traits

overall_design: Physiological mapping identified physiological QTLs (pQTLs) affecting metabolic and physiological traits. Genes with cis-eQTLs mapped within each pQTL may may drive the physiological traits in a causal manner; and was assessed by mediation analysis.

middle: H

first: Leah

middle: C

last: Solberg Wood


title: Methylome analysis by reduced representation bisulfite sequencing (RRBS) from adipose tissue samples of piglets from a swine model of maternal overfeeding and/or restriction

status: Public on Dec 15 2021

city: Salt

first: Abel

last: López-Bermejo

state: Girona

address: Dr. Castany s/n

department: Pediatrics

country: Spain

institute: IDIBGI

summary: Maternal overfeeding  and/or restriction may have effect on the metabolic and epigenetic programming of offspring's adipose tissue. The study tested the potential of postnatal metformin teatment to reverse these changes using a swine animal model.

overall_design: We designed a swine model using pregnant sows distributed in 3 groups of diet intervention (control, overfed and restricted) through pregnancy. At birth, piglets underwent standard lactation without maternal diet intervention. Within each maternal group,  piglets were rambdomly assigned to two different tratment interventions: metformin or vehicle. All piglets were sacrified at weaning and visceral adipose tissue samples were collected.

first: Sílvia

last: Xargay-Torrent


title: Disease duration influences gene expression in neuromelanin-positive cells from Parkinson’s disease patients

status: Public on Nov 08 2021

city: Solna

first: Thomas

last: Perlmann

address: Solnavägen 1

institute: Karolinska Institutet

summary: We used RNAseq to analyze genome-wide gene expression in mDA neurons isolated by LCM from postmortem cases of PD. Patients samples are derived both early after diagnosis and after prolonged disease duration. Cases of ILBD and age-matched controls were also included in the analysis.

overall_design: Neuromelanin-positive dopamine neurons were isolated by laser capture microdissection from post mortem human substantia nigra from Control, PD and ILBD cases.  Several replicates of 100-200 individually isolated mDA neurons per individual (either PD, ILBD or age-matched controls) were collected. . Cortical neurons from control brains (n=18 pools), visualized by Histogene quick staining, were also collected by LCM in order to provide a reference source of mRNA from a brain region devoid of mDA neurons. Libraries for RNA sequencing were generated by the Smart-seq2 protocol.

first: Katarina

last: Tiklova


title: Parallel single cell multi-omics analysis of neonatal skin reveals transitional fibroblast states that restrict differentiation into distinct fates

status: Public on Nov 24 2021

city: Pullman

first: Sean

last: Thompson

address: BLS 240

department: School of Molecular Biosciences

institute: Washington State University

summary: One of the keys to achieving skin regeneration lies within understanding the heterogeneity of neonatal fibroblasts, which support skin regeneration. However, the molecular underpinnings regulating the cellular states and fates of these cells are not fully understood. To investigate this, we performed a parallel multi-omics analysis by processing neonatal murine skin for single-cell ATAC-sequencing (scATAC-seq) and single-cell RNA-sequencing (scRNA-seq) separately. Our approach revealed that fibroblast clusters could be sorted into papillary and reticular lineages based on transcriptome profiling, as previously published. However, scATAC-seq analysis of neonatal fibroblast lineage markers, such as, Dpp4/CD26, Corin, and Dlk1 along with markers of myofibroblasts, revealed accessible chromatin in all fibroblast populations despite their lineage specific transcriptome profiles. These results suggests that accessible chromatin does not always translate to gene expression and that many fibroblast lineage markers reflect a fibroblast state, which includes neonatal papillary, reticular, and myofibroblasts. This analysis also provides a possible explanation as to why these marker genes can be promiscuously expressed in different fibroblast populations under different conditions. Our scATAC-seq analysis also revealed that the functional lineage restriction between dermal papilla and adipocytes fates are regulated by distinct chromatin landscapes. Finally, we have developed a webtool for our multi-omics analysis: https://skinregeneration.org/scatacseq-and-scrnaseq-data-from-thompson-et-al-2021-2/.

overall_design: Trunk skin from 4 wild-type postnatal day 0 mouse littermates were used to generate single-cell suspensions of skin cells. These single-cell suspensions were pooled and parallel scRNA-seq and scATAC-seq experiments were conducted on the same pool of cells. The resulting sequencing data was aligned to the mm10 genome.

first: Quan

last: Phan

first: Sarayut

last: Winuthayanon

first: Iwona

last: Driskell

first: Ryan


title: NKG2D-mediated immunosensing of metabolically stressed hepatocytes by innate-like T cells is essential for initiation of NASH and fibrosis

status: Public on Apr 11 2022

city: Zurich

first: Lukas

middle: Simon

last: Rindlisbacher

address: Winterthurerstrasse 190

department: Experimental Immunology

country: Switzerland

institute: University Zurich

summary: Metabolic-associated fatty liver disease (MAFLD) comprises a spectrum of clinical entries ranging from benign steatosis to cirrhosis. A key event in the pathophysiology of MAFLD is the development of non-alcoholic steatohepatitis (NASH) that may lead to fibrosis and hepatocellular carcinoma. What triggers inflammation in MAFLD is unknown. We find that lipid accumulation in hepatocytes induces expression of ligands for the activating immune receptor NKG2D. Tissue-resident innate-like T cells are activated through NKG2D and secrete IL-17A. IL-17A licenses hepatocytes to produce chemokines that recruit pro-inflammatory cells into the liver, causing NASH and fibrosis. NKG2D-deficient mice did not develop fibrosis in a dietary model for NASH and had a marked decrease in the incidence of hepatic tumors. Importantly, the frequency of IL-17A+ γδ T cells in the blood MAFLD patients correlated with liver pathology. Our findings identify a key molecular mechanism through which stressed hepatocytes trigger inflammation in context of MAFLD.

overall_design: Gene expression analysis using total RNA isolated from murine livers of Klrk1-/- or C57BL6/J mice fed with normal chow diet (NCD) or steatosis-steatohepatitis SSD diet.

first: Felix

last: Wensveen

first: Sonja

last: Marinović


title: RNAseq on Cxcr2hi hepatocytes

status: Public on Nov 02 2021

city: Kansas City

first: David

middle: S

last: Umbaugh

address: 3901 Rainbow Blvd

institute: University of Kansas Medical Center

summary: RNAseq of a novel hepatocyte subpopulation (Cxcr2hi) after acetaminophen exposure (300mg/kg) reveals distinct upregulation of genes involved in macrophage/neutrophil recruitment, specifically Cxcl14.

overall_design: mRNA expression profiles of flow sorted hepatocytes (Cxcr2hi) in APAP and control mice. APAP was administered i.p at 300 mg/kg and hepatocytes were collected via FACs at 24h post APAP.

first: Nga

last: Nguyen


title: Activation of GPR3-b-Arrestin2-PKM2 by DPI enhanced glycolysis in kupffer cells [Human KC]

status: Public on Oct 23 2021

city: Cambridge

first: Guangan

last: Hu

address: 500 Main Street

department: Koch Institute

institute: MIT

summary: To investigate the human primary Kupffer cells from NAFLD patients response to DPI in vitro.

overall_design: Single cells were prepared from human liver biopsies from NAFLD patiehts. Kupffer cells were FAC-sorted by CD14+ and treated with 500nM DPI for 24hrs.  RNA was isolated and purified by Qiagen Rneasy micro kit and applied to RNAseq

first: Jianzhu

last: Chen


title: Activation of GPR3-b-Arrestin2-PKM2 by DPI enhanced glycolysis in kupffer cells

summary: This SuperSeries is composed of the SubSeries listed below.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: External signals regulate continuous transcriptional states in hematopoietic stem cells

first: Eva

last: Fast

address: 1 Portland st

institute: Pfizer

summary: Hematopoietic stem cells (HSCs) must ensure adequate blood cell production following distinct external stressors. A comprehensive understanding of in vivo heterogeneity and specificity of HSC responses to external stimuli is currently lacking. We performed single-cell RNA sequencing (scRNA-Seq) on functionally validated mouse HSCs and LSK (Lin-, c-Kit+,Sca1+) progenitors after in vivo pharmacological perturbation of niche signals interferon, granulocyte-colony stimulating factor (G-CSF), and prostaglandin. We identified six HSC states that are characterized by enrichment but not exclusive expression of marker genes. External signals induced rapid transitions between HSC states but transcriptional response varied both between external stimulants and within the HSC population for a given perturbation. In contrast to LSK progenitors, HSCs were characterized by a greater link between molecular signatures at baseline and in response to external stressors. Chromatin analysis of unperturbed HSCs and LSKs by scATAC-Seq suggested some HSC-specific, cell intrinsic predispositions to niche signals. We compiled a comprehensive resource of HSC- and LSK progenitor-specific chromatin and transcriptional features that represent determinants of signal receptiveness and regenerative potential during stress hematopoiesis.

overall_design: Five male and five female mice were used for each sample. For scATAC-Seq experiment and for HSC replicate 1 scRNA-Seq (HSC_Repl1) mice were left unperturbed. For stimulation scRNA-Seq experiment mice were treated with either 16,16-dimethyl Prostaglandin E2 (dmPGE2), Poly(I:C) (pIC), or G-CSF (GCSF), Indomethacin (indo), or only solvent DMSO as a control (ct). In this experiment HSCs and multipotent progenitors (MPPs) from the same condition (ct, dmPGE2, pIC, GCSF and indo) were extracted from the same mice. The MPP samples were also labeled with hashtag oligonucleotides (HTO) that are part of the Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq) methodology. The two control HSC samples (HSC_Repl1 and HSC_ct = repl2) were treated as two independent biological replicates.


title: Spred1 deficit promotes treatment resistance and transformation of chronic phase CML

status: Public on Sep 30 2021

first: Hsun

last: Ku

summary: Total RNA was extracted from Lin-Sca-1+c-Kit+ (LSK) cells sorted from the BM of Spred1HSCΔ/ΔSCLtTA/BCR-ABL (HSC KO) and Spred1HSCwt/wtSCLtTA/BCR-ABL (HSC wt) (n=5 mice per group, both group given 7 doses of 250μg poly(I:C), ip, every two days, to activate Mx1-cre), Spred1ECΔ/ΔSCLtTA/BCR-ABL (EC KO) and Spred1ECwt/wtSCLtTA/BCR-ABL (EC wt) (n=5 mice per group) mice using the miRNeasy micro Kit (Qiagen, Valencia, CA). SMART-Seq® Ultra Low Input RNA Kit for Sequencing – v4 (TaKaRa, Cat 634888) was used for generating amplified double stranded (ds) cDNA from each sample with 2ng of input total RNA according to the manufacturer's protocol. The resulting ds cDNA was sheared with Covaris LE220 with the setting of DNA fragment size of 200bp peak. The sheared DNA was used for sequencing library preparation by using KAPA HyperPrep Kits (Roche, Cat KK8500). The final libraries were quantified with qubit and bioanalyzer. The sequencing was performed with the single read mode of 51 cycles of read1 and 7 cycles of index read with V4 reagents on Illumina Hiseq2500. Real-time analysis (RTA) 2.2.38 software was used to process the image analysis and base calling. The nf-core RNAseq pipeline v1.3 was used to process the raw sequencing reads (https://nf-co.re). RNA-Seq reads were trimmed to remove sequencing adapters using Trimmomatic3 and polyA tails using FASTP4. The processed reads were mapped back to the mouse genome (mm10) using STAR software (v. 020201)5. The HTSeq software (v.0.6.0)6 was applied to generate the count matrix, with default parameters. Differential expression analysis was conducted by adjusting read counts to normalized expression values using TMM normalization method in R7. Briefly, for each comparison between HSC KO LSKs and HSC wt LSKs and between EC KO LSKs and EC wt LSKs, general linear models were applied to identify DEGs using TMM normalization expression level as depending variable, and genotype as independent variable. Genes with a p-value less than 0.05 and with a fold change (FC) greater than 1.5 or less than 0.7 were considered as significant up- and down-regulated genes, respectively. Pathway analysis was conducted using GSEAPreranked algorithm using GSEA Desktop program in Java8, 9. The former requires a list of up- and down-regulated genes, while the latter a ranked list of whole genes according to their log2 fold change and p-values.

overall_design: To examine gene expresison profiles and upregulated pathways in LSKs (leukemic stem cells) selected from HSC-Spred1 KO CML versus LSKs from HSC-Spred1 wt CML mice, and in LSKs from EC-Spred1 KO CML versus LSKs from EC-Spred1 wt CML mice, and in LSKs from global Spred1 KO CML versus LSKs from Spred1 wt CML mice.

first: Bin

last: Zhang

first: Min-Hsuan


title: SARS-CoV-2 Infection Causes Dopaminergic Neuron Senescence

status: Public on Oct 20 2021

city: New York

first: Shuibing

state: NY

address: A 827B, 1300 York Ave

department: Surgery

institute: Weill Cornell Medical College

summary: Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively permissive to SARS-CoV-2 infection both in vitro and upon transplantation in vivo, and that SARS-CoV-2 infection triggers a DA neuron inflammatory and cellular senescence response. A high-throughput screen in hPSC-derived DA neurons identified several FDA approved drugs, including riluzole, metformin, and imatinib, that can rescue the cellular senescence phenotype and prevent SARS-CoV-2 infection. RNA-seq analysis of human ventral midbrain tissue from COVID-19 patients, using formalin-fixed paraffin-embedded autopsy samples, confirmed the induction of an inflammatory and cellular senescence signature and identified low levels of SARS-CoV-2 transcripts. Our findings demonstrate that hPSC-derived DA neurons can serve as a disease model to study neuronal susceptibility to SARS-CoV-2 and to identify candidate neuroprotective drugs for COVID-19 patients. The susceptibility of hPSC-derived DA neurons to SARS-CoV-2 and the observed inflammatory and senescence transcriptional responses suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients.

overall_design: RNA sequencing

first: Yuling

last: Han

first: Liuliu

last: Yang

first: Tae

middle: W

last: Kim

first: Manoj

last: Nair

first: Oliver

last: Harschnitz

first: Jiajun

last: Zhu

first: Vasuretha

last: Chandar

first: Tuo

first: Wei

first: Feng

last: He

first: Paul

last: van der Valk

first: Maarten

last: Titulaer

first: Jochem

last: Spoor

first: Peter

last: Canoll

first: James

middle: E

last: Goldman

first: Serge

last: Przedborski

first: Robert

last: Schwartz

middle: D

last: Ho

first: Lorenz

last: Studer


title: In vitro exposure of leukocytes to HIV pre-exposure prophylaxis (PrEP) decreases mitochondrial function and alters gene expression profiles.

status: Public on Oct 01 2021

city: Cleveland

first: Mark

last: Cameron

state: OH

address: 10900 Euclid Ave

department: Population and Quantitative Health Sciences

institute: Case Western Reserve University

summary: The use of antiretroviral therapy (ART) as pre-exposure prophylaxis (PrEP) is an effective strategy for preventing HIV acquisition.  The cellular consequences of PrEP exposure, however, have not been sufficiently explored to determine potential effects on health in individuals without HIV.  Peripheral blood mononuclear cells (PBMCs) from people without HIV  were exposed to tenofovir disoproxil fumarate (TDF) or emtricitabine (FTC) overnight.  Mitochondrial mass and function were measured by flow cytometry and Agilent XFp analyzer. Monocyte-derived macrophages (MDMs) were differentiated in 20% autologous serum for 5 days in the presence or absence of TDF or FTC, and surface markers, lipid uptake, and efferocytosis were measured by flow cytometry.  MDM gene expression was measured using RNAseq. Serum lipids were measured using mass spectrometry.  PBMCs exposed to TDF or FTC had decreased maximal oxygen consumption rate (OCR) and reduced mitochondrial mass.  Exposure to PrEP also increased reactive oxygen species (ROS) production from monocyte subsets.  Compared to MDMs cultured in medium alone, cells differentiated in the presence of TDF (829 genes) or FTC (888) genes had significant changes in gene expression.  Further, PrEP-exposed MDMs had decreased mitochondrial mass, and displayed increased lipid uptake and reduced efferocytosis.  Plasma biomarkers and lipid levels were also altered in vivo in individuals receiving a PrEP regimen.  Exposure of leukocytes to TDF or FTC resulted in decreased mitochondrial function, and altered functional and transcriptional profiles.  These findings may have important implications for the metabolic and immunologic consequences of PrEP in populations at risk for HIV acquisition.

overall_design: Comparison of transcriptomic differences among monocyte-derived macrophages isolated from people without HIV and differentiated in the presence of PrEP (FTC and TDF)

first: Emily

middle: R

last: Bowman

first: Cheryl

first: Brian

last: Richardson

first: Manjusha

last: Kulkarni

first: Janelle

last: Gabriel

first: Aaren

last: Kettelhut

first: Lane

last: Hornsby

first: Jesse

last: Kwiek

first: Abigail

middle: N

last: Turner

first: Carlos

last: Malvestutto

first: Jose

last: Bazan

first: Susan

middle: L

last: Koletar

first: Susanne

last: Doblecki-Lewis

first: Michael

middle: M

last: Lederman

first: Nichole

last: Klatt

first: Jordan

last: Lake

first: Nicholas

middle: T

last: Funderburg


title: Fetal brain elicits sexually conflicting transcriptional response to the deficiency of uterine Forkhead Box A2 (Foxa2) in mice

status: Public on Oct 06 2021

city: Columbia

first: Susanta

middle: K.

last: Behura

state: Missouri

address: 920 East Campus Drive

department: Division of Animal Sciences

institute: Univeristy of Missouri

summary: RNA-seq identified different gene sets relating to biological functions such as aging, longevity, and nutrient sensing and signaling that were regulated in a sex-biased manner between the placenta and fetal brain. Conditional knockout of the transcription factor Forkhead Box A2 (Foxa2) in the uterus elicited sexual conflicting expression of those genes between the placenta and fetal brain.

overall_design: The day 15 placenta and brain of male and female fetuses of wild-type (C57BL/6) mice and mice deficent of uterine Foxa2 were analyzed by RNA-seq.

first: Pramod

last: Dhakal

first: Monica

last: Strawn

first: Ananya

last: Samal

middle: K


title: genes differentially expressed between the control mice (rhebFL/FL) and rheb BAD KO mice (Ucp1-cre; rhebFL/FL)

status: Public on Oct 21 2021

city: guangzhou

first: zhipeng

last: zou

state: guangdong

address: tonghe road

department: Cell Biology

institute: southern medical university


title: Activation of GPR3-b-Arrestin2-PKM2 by DPI enhanced glycolysis in kupffer cells [mouse KC]

first: Guangan

last: Hu

summary: To investigate the transcriptional changes of Kupffer cells isolated from HFD-induced obesity mice treated with DPI in vivo.

overall_design: Mice were fed with HFD for total 8 weeks. Mice were dosed with DPI (2mg/kg) every 5 days from week 3. At week 8,  single cells were prepared from mouse livers.  Kupffer cells were FAC-sorted by F4/80+CD11b+. RNA was isolated and purified by Qiagen Rneasy micro kit and applied to RNAseq

first: Jianzhu

last: Chen


title: TTP protects against acute liver failure by regulating CCL2 and CCL5 through m6A RNA methylation

city: Wuhan

first: RUI

last: Zhou

address: Donghu Road 185

institute: Wuhan University

summary: Tristetraprolin (TTP), an important immunosuppressive protein regulating mRNA decay through recognizing the AU-rich elements (AREs) within the 3’UTRs of mRNAs, participates in the pathogenesis of liver diseases. However, whether TTP regulates mRNA stability through other mechanisms remains poorly understood. Here, we report that TTP is upregulated in acute liver failure (ALF), resulting in decreased mRNA stabilities of C-C Motif Chemokine Ligand 2 (CCL2) and C-C Motif Chemokine Ligand 5 (CCL5) through promoting N6-methyladenosine (m6A) mRNA methylation. Overexpression of TTP can markedly ameliorate hepatic injury in vivo. TTP regulates the mRNA stabilization of CCL2 and CCL5. Interestingly, increased m6A methylation in CCL2 and CCL5 mRNAs promotes TTP-mediated RNA destabilization. Moreover, induction of TTP upregulates expression levels of WT1 associated protein (WTAP), Methyltransferase like 14 (METTL14), and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), which encode enzymes regulating m6A methylation, resulting in a global increase of m6A methylation and amelioration of live injury due to enhanced degradation of CCL2 and CCL5. These findings suggest a novel mechanism by which TTP modulates mRNA stabilities of CCL2 and CCL5 through m6A RNA methylation, which is involved in the pathogenesis of ALF.

overall_design: RNA-Seq was performed in  TTP stablely knockdown HL7702 cells.

first: Rui

first: Pingping

last: Xiao

first: Mingxuan

last: Li


title: PPARα and PPARγ activation is associated with pleural mesothelioma invasion, but therapeutic   inhibition is ineffective in preclinical models

status: Public on Nov 14 2021

city: Crawley, Perth

first: Emma

last: de Jong

state: WA

address: 35 Stirling Hwy

institute: University of Western Australia

summary: Mesothelioma is a cancer that typically originates in the pleura of the lungs. It rapidly invades the surrounding tissues, resulting in pain and shortness of breath. We compared mesothelioma cell lines that were injected either subcutaneously or intrapleurally and found that only the latter resulted in invasive and rapid growth. Pleural tumours displayed a transcriptional signature consistent with increased activity of nuclear receptorsPPARα and PPARγ and with an increased abundance of endogenous PPAR-activating ligands. We found that chemical probe GW6471 is a potent dual PPARα/γ antagonist with anti-invasive and anti-proliferative activity in vitro. However, administration of GW6471 at doses that provided sustained plasma exposure levels sufficient for inhibition of PPARα/γ transcriptional activity did not result in significant anti-mesothelioma activity in mice. Lastly, we demonstrate that the in vitro antitumour effect of GW6471 is off-target. We conclude that dual PPARα/γ antagonism alone is not a viable treatment modality for mesothelioma.

overall_design: Examination of invasive and non invasive mesothelioma in murine model

first: M

last: Orozco-Morales

first: Catherine

middle: A

last: Rinaldi

first: Saly

last: Lansley

first: Joel

middle: P

last: Gummer

first: Bence

last: Olasz

first: Shabarinath

last: Nambiar

first: Danika

last: Hope

first: Thomas

last: Casey

first: Y

last: Lee

first: Connull

last: Leslie

first: Gareth

last: Nealon

first: David

last: Shackleford

first: Andrew

last: Powell

first: Marina

last: Grimaldi

first: Patrick

last: Balaguer

first: Rachael

last: Zemek

first: Anthony

last: Bosco

first: Matthew

middle: J

last: Piggott

first: Alice

last: Vrielink

first: Richard

first: W

last: Lesterhuis


title: genes differentially expressed in brown adipose tissue between the control mice (rheb FL/FL) and rheb BAD KO mice (Ucp1-cre; rheb FL/FL)

first: zhipeng

last: zou

summary: RNA sequencing was performed to analyze expression profile in brown adipose tissue with or without rheb knockout.

overall_design: Mice lacking Rheb in the brown adipocyte lineage were generated by mating RhebFL/FL mice with UCP1-Cre conditional knockout mice. Interscapular brown adipose tissue from 3 rheb BAD KO mice or 3 control littermates was pooled, respectively, and extracted for total RNA.

first: Zhipeng

last: Zou

first: Ting

last: Wang


title: genes differentially expressed in bone marrow mesenchymal stem cells (BMSCs) between the control mice (rhebFL/FL) and rheb BAD KO mice (Ucp1-cre; rhebFL/FL)

summary: RNA sequencing was performed to analyze expression profile in BMSCs from mice with or without BAT-specific rheb knockout.

overall_design: Mice lacking Rheb in the brown adipocyte lineage were generated by mating RhebFL/FL mice with UCP1-Cre conditional knockout mice. BMSCs from 2 rheb BAD KO mice and 2 control littermates were extracted for total RNA.


title: Transcriptional analysis of the effect of monoamine oxidase B (MAOB) in human prostate stromal cells (PrSC)

status: Public on Nov 10 2021

city: Spokane

first: Boyang

last: Wu

state: Washington

address: 412 E. Spokane Falls Blvd

summary: The overall goal of this study was to compare gene expression profiles in MOAB-overexpressing PrSC cells and control cells, also to compare gene expression profiles in MAOB-knockdown and control cells.

overall_design: To generate MAOB-overexpressing PrSC cell lines was used a MAOB-expressing lentiviral construct followed by puromycin selection. Stable knock down MAOB PrSC was established using shRNA-expressing lentiviral infection followed by antibiotic selection. Five samples were analyzed by RNA-Seq.


title: Neurofibromin (Nf1) controls metabolic balance and Notch-dependent quiescence of murine juvenile myogenic progenitors [ChIP-seq]

status: Public on Sep 25 2021

city: Berlin

first: Xiaoyan

last: Wei

address: Thielallee 63

institute: Free University of Berlin

summary: We conclude that Nf1Myf5 MPs are driven towards quiescence and show metabolic reprogramming with severely inhibited glycolytic metabolism that, in turn impinges on H4K16ac decoration and expression of myogenic differentiation-related genes. ChIP-Seq analysis of freshly isolated p7 MPs showed apparently unaltered H3K4me3 levels between controls and Nf1Myf5 MPs, while H3K27me3 levels were globally reduced in Nf1Myf5 MPs. A reduction of H3K27me3 decoration was observed at genes associated with quiescence as Pax7, or with cell cycle repression as Cdkn2a. The assumption of a quiescent state in Nf1Myf5 MPs is concomitant to decreased repressive H3K27me3 modification at quiescence-associated genes.

overall_design: Three histone modification marks (Histone 3 Lysine 4 trimethylation, Histone 3 Lysine27 trimethylation and Histone 4 Lysine16 acetylation) status were compared through ChIP-Seq analysis between freshly FACS sorted p7 controls and Nf1Myf5 MPs.

first: Sigmar

last: Stricker


title: Spatial transcriptomics of Cutaneous and Systemic Lupus Erythematosus skin

city: Seattle

first: Liang

last: Zhang

address: 530 Fairview Ave N

institute: NanoString

summary: We performed spatial transcriptomics on a case series of different clinical subtypes of cutaneous lupus erythematosus including acute cutaneous lupus erythematosus (malar rash, systemic lupus erythematosus). Our goals were to (1) determine which differentially expressed genes (DEGs) could be attributed to specific cell populations in specific locations within the tissue, (2) determine if spatial transcriptomics could better distinguish between CLE clinical subtypes than bulk RNA approaches and (3) examine potential cell-cell communication pathways within the skin lesions.

overall_design: NanoString Digital Spatial Profiling (DSP) with Whole Transcriptome Atlas (WTA) was performed on 4 chronic/discoid lupus erythematosus (CCLE/DLE), 3 subacute cutaneous lupus erythematosus (SCLE) and 3 acute cutaneous lupus erythematosus (ACLE/SLE) patient skin biopsies compared to 3 healthy controls (skin cancer excision healthy/clear margins).

first: Jillian

last: Richmond

first: April

last: Deng


title: Neurofibromin (Nf1) controls metabolic balance and Notch-dependent quiescence of murine juvenile myogenic progenitors [MeDIP-Seq]

summary: We conclude that the epigenetic alterations we observed in Nf1Myf5 MPs are in line with a shift towards a quiescent state, and that these alterations could contribute to impaired myogenic differentiation. Furthermore, hypermethylation and transcriptional downregulation of metabolic genes points towards changes in cellular energy metabolism in Nf1Myf5 MPs.

overall_design: We compared differential genomic DNA methylation level between controls and Nf1Myf5 freshly isolated p7 MPs through MeDIP-Seq analysis.


title: Neurofibromin (Nf1) controls metabolic balance and Notch-dependent quiescence of murine juvenile myogenic progenitors [RNA-seq]

summary:
Purpose: To study Nf1 regulated pathways in controlling juvenile satellite cells quiescence induction.
Methods: We sequenced total mRNAs isolated from juvenile satellite cells FACS sorted from postnatal day 7 Control (Nf1flox/+ Myf5Cre+) and KO (Nf1flox/flox Myf5Cre+) mouse hindlimb skeletal muscle.
Results: Our study suggests that Nf1 is required for maintaining the balance between quiescence induction and amplification / differentiation in the postnatal MP pool.
Conclusions: The tumor suppressor Nf1 maintains the myogenic progenitor (MP) pool during postnatal muscle development.

overall_design: mRNA profiles of FACS sorted juvenile satellite cells isolated from 7-day-old Control (Nf1flox/+ Myf5Cre+) and Nf1 KO (Nf1flox/flox Myf5Cre+) mice.


title: Early alterations in lipid metabolism in the spinal cord of SOD1 mice

status: Public on Sep 27 2021

city: Madrid

first: Silvia

last: Corrochano

address: Calle del Prof Martín Lagos

department: Neurología

institute: Instituto de Investigación Sanitaria del Hospital Clínico San Carlos

summary: Amyotrophic lateral sclerosis (ALS) is a multifactorial and complex fatal degenerative disorder. A number of pathological mechanisms that lead to motor neuron death have been identified, although there are many unknowns in the disease aetiology of ALS. Alterations in lipid metabolism are well documented in the progression of ALS, both at the systemic level and in the spinal cord of mouse models and ALS patients. The origin of these lipid alterations remains unclear. This study aims to identify early lipid metabolic pathways altered before systemic metabolic symptoms in the spinal cord of mouse models of ALS. To do this, we performed a transcriptomic analysis of the spinal cord of SOD1G93A mice at an early disease stage(p90)

overall_design: Spinal cord mRNA profiles of 90 days old wild type (WT) and SOD1 G93A  female mice(SOD1)

first: Luis

last: Fernández

first: Debbie

last: Williams


title: Small Molecule Inhibitors that Disrupt the MTDH-SND1 Complex Suppress Breast Cancer Progression and Metastasis

status: Public on Sep 07 2021

city: Plainsboro

first: Yong

state: NJ

address: LTL227 Wathington Road

department: Molecular Biology

institute: Princeton University

summary:
Previous studies discovered that MTDH frequently amplifies and overexpresses in breast cancer in human patients and is strongly associated with higher metastasis and treatment failure and thereby leads to poor prognosis.
In mouse mammary tumor models, knockout of Mtdh substantially reduces tumor incidence and suppresess metastasis. Furthermore, Mtdh interact with Snd1 and the interaction appears essential for its tumor promoting function.
To develop novel therapeutics targeting Mtdh function, small molecular compound to disrupt the Mtdh-Snd1 interaction was identified by high throughput screen.
To further elucidate the mechanism of MTDH targeting caused anti-tumor activity and to confirm the action mode of the small molecular compound C26A6 as a Mtdh-Snd1 disruptor, transcriptome changes in mouse mammary tumors following treatments of C26A6 and acute induction of Mtdh knockout by Tamoxifen treatment were investigated using next generation sequencing.

overall_design: MTDH targeting induced mammary tumor transcriptome changes were determined by RNAseq profiling. 3 treatment groups of C26A6, Tamoxifen and vehicle control (corn oil+saline) (n=4 each group) were tested.

first: Minhong

last: Shen


title: Effects of targeting MTDH-SND1 interaction in mammary tumor cell and normal mammary epithelial cell in 3D culture in vitro

summary:
Therapeutic targeting MTDH-SND1 interaction Suppresses   Breast Cancer Progression and Metastasis (GSE159764). To further elucidate the tumor intrinsic effects of the targeting and the adverse effects on normal mammary epithelial cells
Mouse mammary tumor cells and normal mammary epithelial cells were isolated from transgenic mouse models and cultured in vitro 3D spheroids system.
MMTV-PyMT tumor cells from cKO mouse in tumorsphere culture were treaed with tamoxifen to induce Mtdh KO, and compared to the mock treatment which maintain wild type Mtdh. Thus the tumor intrinsic effects can be determined
Normal mammary epithelial cells were isolated from mouse mammary gland and cultured in vitro in mammosphere. The cells were treated with inhibitor C26A6 vs control and thus the adverse effects on normal MECs can be determined.

overall_design:
Two pair four groups. Duplicate samples for each group.C26A6 treatment. Each group has duplicate samples
PyMT tumorsphere pair includes control vs tamoxifen treatment induced KO; normal mammary epithelial mammosphere pair includes control vs inhibitor


title: Activation of GPR3-b-Arrestin2-PKM2 by DPI enhanced glycolysis in kupffer cells [single-cell RNA-seq]

first: Guangan

last: Hu

summary: Single-cell RNAseq analysis of liver cells from NASH and cirrhosis patients has identified the presence of TREM2+ disease-associated macrophages (DAMs) in the liver that display lower expression of metabolic genes. To determine whether the DAMs are also present in patient with mild NFALD, we performed scRNAseq of freshly isolated immune cells from liver biopsies of 3 healthy donors and 3 mild NFALD patients. Kupffer cells were specifically focused.

overall_design: FAC-sorted CD45+ immune cells from human livers from healthy donors and NAFLD patiehts. Single cells were applied to single cell RNAseq.

first: Jianzhu

last: Chen


title: Genes differentially expressed in brown adipose tissue between the control mice (rhebFL/FL) and rhebAD KO mice (fabp4-cre; rhebFL/FL)

status: Public on Sep 03 2021

summary: expression profile of brown adipose tissue (interscapular) from the control or rhebAD KO mice was analyzed by mRNA array.

overall_design: Mice lacking Rheb in the adipocyte lineage were generated by mating RhebFL/FL mice with fabp4-Cre conditional knockout mice. Interscapular brown adipose tissue from 3 rhebAD KO mice or 3 control littermates was pooled, respectively, extracted for total RNA, followed by mRNA array analysis.


title: Isolation and expansion of murine γδ T cells from mouse splenocytes

status: Public on Aug 29 2021

city: Duarte

first: Hsun

middle: Teresa

last: Ku

state: CA

address: 1500 E. Duarte Road

institute: City of Hope

summary:
Purpose: To characterise gene expression of in vitro expanded mouse gammadelta T cells.
Methods: Freshly isolated and IL-2 expanded gammadelta T cells, single samples, and total RNA was isolated and sequenced.
Results: High upregulation of Th1 like genes including several granzymes genes.
Conclusion: Expanded gammadelta T cells express Th1-like genes.

first: Maciej

last: Kujawski

first: Kenneth

last: Dery

first: John

last: Shively


title: Single-cell RNA sequencing analysis of transgenic zebrafish embryo/larvae

status: Public on Aug 23 2021

city: Bronx

first: Teresa

last: Bowman

state: New York

address: 1300 Morris Park Avenue

department: Developmental and Molecular Biology

institute: Albert Einstein College of Medicine

summary: The purpose of the experiment was to define the heterogeneity of hematopoietic stem and progenitor cells (HSPC) at emergence and initial maturation using scRNA-Seq of enriched blood populations from transgenic fluorescent zebrafish (30 and 52 hpf). Results provide insight into the different HSPC populations in heamtopoietic development.

overall_design: 10X Single-cell RNA sequencing from sorted hematopoeitic stem and progenitor cells from transgenic fluorescent zebrafish at 30 and 52 hpf, using Illumina HiSeq. Samples conducted in replicate.

middle: V

first: Bianca

last: Ulloa


title: Insights into the regulation of the brain-placental axis

status: Public on Aug 27 2021

first: Susanta

last: Behura

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Neurofibromin (Nf1) controls metabolic balance and Notch-dependent quiescence of murine juvenile myogenic progenitors

first: Xiaoyan

last: Wei


title: RNA sequencing analysis of postmortem human Brodmann Area 9 in the University of Texas Health Science Center at Houston Brain Collection

status: Public on Aug 20 2021

city: Houston

first: Consuelo

last: Walss-Bass

state: Texas

address: 1941 East Road Rm. 3110

department: Louis A. Faillace Department of Psychiatry and Behavioral Sciences

summary:
From Mendez et al 2021 "Angiogenic Gene Networks are Dysregulated in Opioid Use Disorder: Evidence from Multi-Omics and Imaging of Postmortem Human Brain": Opioid use disorder (OUD) is a public health crisis in the U.S. that causes over 50 thousand deaths annually due to overdose. Using next-generation RNA sequencing and proteomics techniques, we identified 394 differentially expressed (DE) coding and long noncoding (lnc) RNAs as well as 213 DE proteins in Brodmann Area 9 of OUD subjects. The RNA and protein changes converged on pro-angiogenic gene networks and cytokine signaling pathways. Four genes (LGALS3, SLC2A1, PCLD1, VAMP1) were dysregulated in both RNA and protein. Dissecting these DE genes and networks, we found cell type specific effects with enrichment in astrocyte and endothelial correlated genes. Weighted-genome correlation network analysis (WGCNA) revealed cell type correlated networks including an astrocytic/endothelial network involved in angiogenic cytokine signaling as well as a neuronal network involved in synaptic vesicle formation. In addition, using ex vivo magnetic resonance imaging, we identified increased vascularization in postmortem brains from a subset of subjects with OUD. This is the first study of its kind relating dysregulation of astrocytic and endothelial angiogenic gene networks in OUD with ex vivo imaging qualitative evidence of hypervascularization in postmortem brain. Understanding the neurovascular effects of OUD is critical in this time of widespread opioid use.
This dataset includes Samples from Mendez et al 2021 "Angiogenic gene networks are dysregulated in opioid use disorder: evidence from multi-omics and imaging of postmortem human brain" published in Molecular Psychiatry. doi: 10.1038/s41380-021-01259-y
For full sample information for each sample, please contact Dr. Walss-Bass at consuelo.walssbass@uth.tmc.edu

overall_design: In total, raw fastq for 41 samples (27 opioid users and 14 nonpsychiatric controls as determined by postmortem consensus diagnosis of 2 trained psychiatrists) from the UTHealth Brain Collection are included and were used in Mendez et al 2021 and have processed counts provided. These counts were used to generate the conclusions in the manuscript.

first: Emily

last: Mendez

first: Haichao

first: Jiaqian

last: Wu


title: Replacement of nitrite in meat products by natural bioactive compounds results in reduced exposure to N-nitroso compounds: the PHYTOME project

status: Public on Aug 17 2021

city: Maastricht

first: Simone

middle: G

last: van Breda

state: Limburg

address: Universiteitssingel 50

department: Toxicogenomics

institute: Maastricht University

summary: It has been proposed that endogenously formed N-nitroso compounds (NOCs) are partly responsible for the link between red meat consumption and colorectal cancer (CRC) risk. As nitrite has been indicated as one of the critical factors in the formation of endogenous NOCs, it is of high importance to replace or reduce the nitrite levels in meat. Therefore, the PHYTOME project was initiated (Phytochemicals to reduce nitrite in meat products; www.phytome.eu), an EU funded research project aiming to develop innovative meat products in which the food additive sodium nitrite (E251) has been replaced by natural compounds originating from fruits and vegetables. A human dietary intervention study was conducted in which healthy subjects consumed 300 grams of meat for two weeks, in subsequent order: normal processed red meat, white meat, and red processed meat with standard or reduced levels of nitrite and added phytochemicals. Consumption of standard-nitrite PHYTOME meat products leads to a significant reduction in Apparent Total N-nitroso Compounds (ATNC) levels in faecal water, a surrogate marker of endogenously formed NOCs, as compared to the consumption of conventional processed red meat products. A reduction of nitrite in the PHYTOME meat lowered these levels even further. In addition, DNA strand breaks induced in ex-vivo faecal water exposed Caco-2 cells and O6-methyl-guanine adducts levels in colonic DNA were significantly higher after consumption of normal processed red meat as compared to white meat intake. PHYTOME meat intake resulted in reduced levels of these genotoxic markers, however, these were not statistically significant. Whole genome gene expression analyses in colonic tissue identified differentially expressed genes and genes associated with ATNC, which are related to molecular pathways which may explain cancer risk initiation after intake of processed red meat and cancer risk prevention after intake of the PHYTOME meat. Together these results indicate that addition of natural extracts to conventional processed red meat products results in reduced endogenous formation of NOCs, and may therefore contribute to a reduced risk of CRC, which is mechanistically supported by gene expression analyses.

overall_design: The human dietary intervention study has a parallel design. There are 2 study groups (1 and 2), and in each study group there are 2 meat intervention periods (A and B), separated by a wash-out period (O). During intervention period “A”, participants were asked to consume the provided red processed meat products (red processed meat group), while in period “B” red processed meat products enriched with natural compounds were provided. For study group 1, the meat products of both period ”A” and “B” had standard nitrite levels (standard nitrite PHYTOME meat), while in study group 2 the nitrite levels in period “B” were reduced (reduced nitrite PHYTOME meat). At the beginning of the study and after each intervention period of 2 weeks, colonic biopsies were collected during an endoscopic examination and analysed for gene expression changes.


title: CD4+ T cells contribute to neurodgeneration in Lewy Body dementia

status: Public on Sep 14 2021

city: Stanford

first: Emma

last: Tapp

email: etapp@stanford.edu, dgate@stanford.edu

state: California (CA)

address: 290 Jane Stanford Way

department: Neurology

institute: Stanford University

summary: Recent studies indicate a role of the adaptive immune system in Lewy body dementia (LBD). However, the mechanisms regulating T cell brain homing in LBD remain unknown. Here, we demonstrate interaction of T cells with Lewy bodies and with dopaminergic neurons in post-mortem LBD brains. Single cell RNA sequencing of cerebrospinal fluid (CSF) cells identified upregulated expression of C-X-C Motif Chemokine Receptor 4 (CXCR4) in CD4+ T cells in LBD. CSF protein levels of the CXCR4 ligand, C-X-C Motif Chemokine Ligand 12 (CXCL12) were associated with neuroaxonal damage in LBD. Finally, we demonstrate clonal expansion and upregulated Interleukin 17A by CD4+ T cells stimulated with phosphorylated α-synuclein. Cumulatively, these results indicate CXCR4-CXCL12 signaling as a mechanistic target for inhibiting pathological T cell trafficking in LBD.

overall_design: Examination of transcriptional profile of cells from the cerbrospinal fluid of healthy and diseased patients

first: Gate

last: David

first: Tapp

last: Emma