title: Feedback regulation of RNase E during UV-stress response in cyanobacteria

status: Public on Oct 22 2021

city: Freiburg

first: Jens

last: Georg

address: Schänzlestr. 1

institute: University of Freiburg

summary: Endoribonucleases govern the maturation and degradation of RNA and are indispensable in the post-transcriptional regulation of gene expression. A key endoribonuclease in many bacteria is RNase E. To ensure an appropriate supply of RNase E, some bacteria such as E. coli have evolved a tightly functioning feedback regulation of RNase E, which is mediated in cis by the rne 5′-untranslated region (5′UTR); however, the mechanisms involved in the control of RNase E in other bacteria have largely remained unknown. Cyanobacteria rely on solar light as energy source for their photosynthetic lifestyle, despite the inherent ultraviolet (UV) irradiation. Here, we revealed the global gene expression response in the cyanobacterium Synechocystis sp. PCC 6803 after exposure to UV light and discovered a unique response of RNase E: a rapidly increasing enzymatic activity although stability of the protein was lowered  . In parallel, we observed a substantial   stabilization of the full-length mRNA specifically after UV-C treatment, while the 5′UTR accumulated under all conditions. Mapping of RNA 3′ends and in vitro cleavage assays revealed that RNase E cleaves within a stretch of six consecutive uridine residues within the rne 5′UTR, indicating the autoregulation of RNase E via its own 5′UTR. These observations imply that RNase E in cyanobacteria evolved as a substantial contributor in re-shaping the transcriptome during the UV stress response, that its required activity level is maintained despite enhanced turnover of the protein, and that the underlying mechanism involves a feedback mechanism acting on a uridine-rich element within the rne 5′UTR.

overall_design: We performed microarray analysis of total RNA from UV-stressed cultures and cultures that were not dtressed (mock). Sampling time points were t1 = 1h +/- UV, t2 = 2h +/- UV. Samples were taken in biological duplicates.

first: Satoru

last: Watanabe

first: Damir

last: Stazic

first: Shota

last: Ohtake

first: Megumi

last: Numakura

first: Munehiko

last: Asayama

first: Taku

last: Chibazakura

first: Annegret

last: Wilde

first: Claudia

last: Steglich

first: Wolfgang

middle: R

last: Hess


title: Aortic gene expression profiles of double ApoE and ApoA-I knockout mice

status: Public on Nov 22 2021

city: Milan

first: Stefano

last: Manzini

address: via Balzaretti, n. 9

department: DISFEB

country: Italy

institute: University of Milan

type: Expression profiling by high throughput sequencing

summary: Eight weeks old double apolipoprotein E and apolipoprotein A-I knockout mice (DKO) were fed either normal laboratory diet (chow) or high-fat (Western) diet for 6 or 22 weeks. High-throughput sequencing technologies were used to analyse the transcriptome of the aorta of apolipoprotein E knockout (EKO, GSE163657) and DKO mice to showcase the use of the software reString (https://github.com/Stemanz/restring), a functional enrichment results aggregator.

overall_design: RNA-seq performed in mouse whole aortas from double apolipoprotein E and apolipoprotein A-I knockout mice (DKO), n=3-4 per experimental group, using the Illumina Genome Analyzer IIx. Two diets (chow, Western), two time points (6 weeks, 22 weeks).

first: Marco

last: Busnelli

first: Giulia

last: Chiesa


title: Methylation studies in mole rats. Part 2

status: Public on Oct 18 2021

city: Los Angeles

first: Steve

last: Horvath

state: CA

address: 695 Charles E. Young Drive South, Box 708822

department: Human Genetics

country: USA

institute: University of California, Los Angeles

summary:
An Infinium microarray platform (GPL28271, HorvathMammalMethylChip40) was used to generate DNA methylation data from many tissues of 3 species of mole rats: Cape mole rat (Georychus capensis), Damaraland mole rat (Cryptomys damarensis),  Naked mole rat (Heterocephalus glaber). We generated DNA methylation data from n=94  tissues from 3 species: Cryptomys damarensis (n=10), Georychus capensis (n=6), Heterocephalus glaber (n=78).  All tissues ewere obtained from frozen tissue collection that were euthanized for other studies. Kidney (n=6), liver (n=61), skin (n=27).
The tissues used in this study were obtained from post-mortem specimens from animals free from disease in compliance. Sample collection was from post-mortem material. Tissue samples were snap frozen in liquid nitrogen following dissection and transferred for storage at -80ºC.  Genomic DNA was extracted using Qiagen DNeasy Blood and Tissue kit and quantified using Nanodrop and Qubit.als

sample_organism:
Georychus capensis
Heterocephalus glaber
Fukomys damarensis

platform_organism:
Homo sapiens
Mus musculus
Rattus norvegicus

overall_design:
Genome annotations of the mammalian methylation array can be downloaded from https://github.com/shorvath/MammalianMethylationConsortium
The characteristics: Queen pertains to female naked mole rats. Queen=yes indicates that the female is a breeding queen. Queen=no indicates that the animal is a non-breeding female. NA=not applicable (e.g. male) or unknown.
The characteristics: ConfidenceInAgeEstimate with numeric value between 0 and 100. It indicates the confidence in the accuracy in the age estimate. This value was assigned by the team of investigators. It is based on their subjective confidence in the accuracy of the record when it comes to the chronological age at the time of samle collection. A value of 100 was chosen for samples whose birthday and death date was accuratly kown. We only used samples with a confidence of 90 or higher when building or evaluating DNA methylation based age estimators or when conducting epigenome wide association studies of chronological age.
The characteristics: Age represents chronological/calendar age of the animal at the time of sample collection. Age is in units of years.

first: Chris

last: Faulkes


title: Single-cell RNA-Sequencing maps the hematopoietic landscape in naked mole-rats.

status: Public on Oct 15 2021

city: Rochester

first: Stephan

last: Emmrich

state: NY

address: 213 Hutchison Hall, River Campus

institute: University of Rochester

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

sample_organism:
Mus musculus
Heterocephalus glaber

platform_organism:
Mus musculus
Heterocephalus glaber

overall_design: Refer to individual Series


title: Single-cell RNA-Sequencing maps the hematopoietic landscape in naked mole-rats [unfractionated LY]

summary: Naked mole-rats are a mammalian model organism of exceptional longevity. We mapped the T cell developmental landscape in Naked mole-rats and showed

overall_design:
Naked mole-rat or Mouse lymphatic tissues were extracted, RBC-lysed and submitted to scRNA-Seq as unfractionated thymus or lymph nodes, in parallel FACS-antibodies were conjugated to oligo-ADT tags to quantify surface marker binding as described for CITE-Seq. The mRNA libraries were aligned to either the FRAMA bone marrow transcriptome assembly from our publication or a mouse genome reference.

Note: Raw data represents only gene expresion (GEX). Raw data for ADT not included.


title: Identifying molecular changes in early cervical cancer samples of patients that developed metastasis

status: Public on Jan 03 2022

city: Rotterdam

first: Willem

last: de Koning

state: Zuid-Holland

address: Doctor Molewaterplein 40

country: Netherlands

institute: Erasmus University Medical Center

summary: Cervical cancer is one of the most common cancers in women worldwide. Patients  diagnosed with early-stage cervical cancer have a good prognosis, however, 10-20%  suffer from local or distant recurrent disease after primary treatment. Treatment options for  recurrent cervical cancer are limited. Therefore, it is crucial to identify factors that can  predict patients with an increased risk of recurrence to optimize treatment to prevent the  recurrence of cervical cancer. We aimed to identify biomarkers in early-stage primary  cervical cancer which recurred after surgery. Formalin-Fixed, Paraffin-Embedded surgical  specimens of 34 patients with early-stage cervical cancer (FIGO 2009 stage 1B1) and 7  healthy controls were analyzed. Targeted gene expression profiling using the PanCancer  IO 360 panel of NanoString Technology was performed. The findings were confirmed by  performing immunohistochemistry stainings. Various genes, namely GLS, CD36, WNT5a,  HRAS, DDB2, PIK3R2, and CDH2 were found to be differentially highly expressed in  primary cervical cancer samples of patients who developed distant recurrence. In  addition, The relative infiltration score of CD8+ T cells, CD80+CD86+ macrophages,  CD163+MRC1+ macrophages, and FOXP3+IL2RA+ regulatory T cells were significantly  higher in this group of samples. In contrast, no significant differences in gene expression  and relative immune infiltration were found in samples of patients who developed local  recurrence. The infiltration of CD8 and FOXP3 cells were validated by  immunohistochemistry using all samples included in the study. We identified molecular  alterations in primary cervical cancer samples from patients who developed recurrent Q9  disease. These findings can be utilized towards developing a molecular signature for the  early detection of patients with a high risk to develop metastasis.

overall_design: RNA was extracted from FFPE samples (healthy n=7*2, CCLR n=14, CCDR n=8, CCNR n=12)

first: Vera

last: de Geus

first: Patricia

last: Ewing-Graham

first: Maurits

middle: N

first: Thierry

middle: P

last: van den Bosch

first: Alex

last: Nigg

first: Casper

middle: H

last: van Eijck

first: Marta

last: Jozwiak

first: Heleen

middle: J

last: van Beekhuizen

first: Dana

middle: A

last: Mustafa


title: Mesomelic Dysplasias Associated With The HOXD Locus Are Caused By Regulatory Reallocations [ChIP-Seq]

status: Public on Jul 20 2021

city: Lausanne

first: Lucille

last: Lopez-Delisle

address: Station 19

country: Switzerland

institute: EPFL

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Some human families display severe shortening and bending of the radius and ulna, a condition referred to as mesomelic dysplasia. Many of these families contain chromosomal rearrangements at 2q31, where the human HOXD locus maps. In mice, the dominant X-ray-induced Ulnaless inversion of the HoxD gene cluster produces a similar phenotype suggesting that the same pathological mechanism is at work in humans and mice. A tentative hypothesis was proposed where the various alterations to the genomic structure of HOXD could translocate Hoxd13 near to proximal limb enhancers, leading to its deleterious gain-of-expression in the embryonic forelimb. We evaluated this hypothesis by engineering a ca. 1Mb large inversion including the HoxD gene cluster, in order to position Hoxd13 within a chromatin domain rich in proximal limb enhancers. We show that these enhancers contact and activate Hoxd13 in proximal cells, concomitant to the formation of a mesomelic dysplasia phenotype. A secondary mutation in the coding frame of the HOXD13 protein in-cis with the inversion completely rescued the limb alterations, demonstrating that ectopic HOXD13 is indeed the unique cause of this bone anomaly. Single cell expression analysis and evaluation of HOXD13 binding sites in cells from this ectopic expression domain suggests that the phenotype arises primarily by acting through genes normally controlled by HOXD13 in distal limb cells. Altogether, these results provide a conceptual and mechanistic framework to understand and unify the molecular origins of human mesomelic dysplasia associated with 2q31.

relation:
Reanalysis of: GSM3504924
Reanalysis of: GSM3504925
SubSeries of: GSE165495

overall_design: Reanalysis of part of GSM3504924 and GSM3504925 (25 million reads from SRR8290670 and 25 million reads from SRR8290672) to be compared to CUT&RUN HOXD13. All steps of analysis are available in https://github.com/lldelisle/scriptsForBoltEtAl2021/blob/main/CUTandRUN/01_analysis_on_galaxy.sh .

first: Christopher

middle: C

last: Bolt

first: Bénédicte

last: Mascrez

first: Denis

last: Duboule


title: Germline-like TCR alpha chains dominate shared self-reactive T cell receptors in type 1 diabetes

status: Public on Dec 15 2021

city: Seattle,

first: Stephanie

last: Osmond

state: WA

address: 1201 9th Ave

institute: Benaroya Research Institute

summary: Human islet antigen reactive CD4+ memory T cells (IAR T cells) play a key role in the pathogenesis of autoimmune type 1 diabetes (T1D). Using single cell RNA-sequencing (scRNA-seq) to identify T cell receptors (TCRs) in IAR T cells, we have identified a class of TCRs that share TCR alpha chains between individuals (“public”).

overall_design: 2767 cells total were sequenced. Cells were collected from 12 healthy, 24 new-onset, and 12 established T1D donors.

first: Peter

middle: S

last: Linsley

first: Fariba

last: Barahmand-pour Whitman

first: Elisa

last: Balmas

first: Hannah

last: DeBerg

first: Kaitlin

last: Flynn

middle: K

last: Hu

first: Mario

middle: G

last: Rosasco

first: Janice

last: Chen

first: Colin

last: O'Rourke

first: Elisavet

last: Serti

first: Vivian

last: Gersuk

first: Keshav

last: Motwani

first: Howard

last: Seay

first: Todd

middle: M

last: Brusko

first: William

middle: W

last: Kwok

first: Cate

last: Speake

first: Carla

last: Greenbaum

first: Gerald

middle: T

last: Nepom

first: Karen

last: Cerosaletti


title: Selection Pressures in the Aged Microenvironment Drive Transformation of Dnmt3a-Mutant Hematopoietic Stem Cells to Myeloid Malignancy

status: Public on Jul 15 2021

city: Bar Harbor

first: Jennifer

last: Trowbridge

state: ME

address: 600 Main Street

institute: The Jackson Laboratory

summary: Driver somatic mutations in adult acute myeloid leukemia (AML) are often preceded by a benign or premalignant state termed clonal hematopoiesis (CH) for which the greatest risk factor is aging. To risk-stratify aged individuals and develop therapies to prevent AML, we need to understand the variables that promote transformation from CH to AML. Using our orthogonally inducible Dnmt3aR878H;Npm1cA-mutant model of progression from CH to myeloid malignancy, we find that in young mice, Dnmt3a mutation buffers against myeloid differentiation, proliferation, acquisition of cooperating mutations and transformation induced by stress, inflammation, and the oncogenic Npm1 mutation. However, when Dnmt3a;Npm1-mutant hematopoietic stem cells (HSCs) are transplanted into naturally aged recipient mice, they gain myeloid-biased differentiation capacity and have an accelerated transformation to AML. These results support the hypothesis that alterations in the aged microenvironment drive risk of AML in individuals with CH and help to explain why this Dnmt3a mutation is exceedingly rare in pediatric leukemias.

overall_design: 4 control and 3 mutant LTHSC, 3 control 4 mutant STHSC, 3 control and 3 mutant MPP3, 4 mutant and 4 control MPP4 from young 6 week post PIPC mice.

last: SanMiguel


title: Gene Expression Profile From 15 day Embryonic Mouse Eyes

status: Public on May 12 2021

city: LOS ANGELES

first: SONIA

last: GUHA

address: 650 Charles E Young Dr, S

department: Ophthalmology, SEI

institute: UCLA

summary:
Absence of Ocular albinism type 1 (Oa1) gene is associated with abnormal pigmentation and misrouting of retinal ganglion cell (RGC) axons at the optic chiasm of the brain. Expression of the Oa1 gene is tightly correlated with development of RGCs. In mice the Oa1 gene is expressed at embryonic day (E) 10.5. Soon afterwards the RGCs appear and at E15.5 majority of their axons pass through the optic chiasm. So comparison of microarrays hybridized with mRNAs from E15.5 Ocular albino (Oa1-/-) and Wild Type (WT) mice eyes will help us identify candidate genes critical for Ocular albinism.
We used microarray analysis to study the differential expression of genes between E15.5 eyes from Wild type and Oa1-/- mice.

overall_design: Six pregnant females, three Oa1-/- and three WT, were sacrificed at day 15.5 days post coitum. Eyes from six embryos from each pregnant mouse were isolated and treated as one biological sample. After enucleation, the anterior segments were dissected out. RNA was extracted from the posterior eye segments of each of 3 Oa1-/- (T1, T2, T3) and 3 WT (C1, C2, C3) sample and hybridized to Affymetrix microarrays.

first: Sonia

last: Guha

first: Debora

last: Farber


title: Gene expression profiles in replicative senescence in TIG-3 cells

city: Hiroshima

first: Kimiyoshi

last: Yano

address: Kasumi 1-2-3, Minami-ku

country: Japan

institute: Hiroshima University

summary: A comparative alalysis of the gene expressions between young and senescent TIG-3 cells was performed to identify key genes regulating cellular senescence.

overall_design: TIG-3 cells at 41 PDL and 77 PDL were used as young and senescent cells, respectively. Total RNAs from these cells were purificated using ISOGEN II. Microarray analysis of mRNA expression levels was performed using 3D-Gene human oligo chip 25k V2.1.

first: K

first: R

middle: U

last: Takahashi

first: B

last: Shiotani

first: J

last: Matsunaga

first: T

last: Shidooka

first: Y

last: Sudo

last: Yamamoto

first: S

last: Kan

first: H

last: Sakagami

last: Tahara


title: Response of human iPSCs-derived macrophages to apoptotic cells, role of ACK1 and BRK tyrosine kinases

status: Public on Dec 31 2021

city: New York

first: Bic

last: MSKCC

address: 1275 York Ave.

institute: Memorial SLoan-Kettering Cancer Center

summary: lupus project

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: differential response to apoptotic cells at 90 minutes of WT macrophages or mutant ACK1 and BRK macrophages and WT macrophages treated with ACK1 or BRK inhibitors

first: Stephanie

last: Guillet

first: Frederic

last: Geissmann


title: Cell-type specific regulation mechanisms of depression in the nucleus accumbens

status: Public on Jul 09 2021

city: Phoenix

first: Hee-Dae

last: Kim

state: AZ

address: 425 N 5th St

department: Basic Medical Sciences

institute: University of Arizona College of Medicine

summary: Background: Depression is the leading cause of disability which produces enormous health and economic burdens. In the reward circuitry, the nucleus accumbens (NAc) is a key brain region of depression pathophysiology, possibly based on differential activities of D1- or D2-type medium spiny neurons (MSNs).  Methods: To separate D1- or D2-MSN specific transcriptomes in the NAc, RiboTag (RT) mice were crossed with D1- or D2-Cre lines and subjected to chronic social defeat stress. The cell-type specifically tagged ribosome-mRNA complex was pulled down by anti-HA antibody, and purified RNAs were subjected to RNA sequencing. Sequencing data were analyzed and defined differentially expressed genes (DEGs) were validated with RNAscope and viral overexpression in vivo.  Results: Both MSN subtypes express distinct gene expression profiles according to stress groups. The DEGs are correlated with depression relevant gene ontology terms. Behavioral susceptibility and resilience are also correlated with subsets of DEGs, especially in D1-MSNs.  Conclusions: Distinct subsets of genes are modulated in a cell-type specific manner in the NAc of depressed mice. Here we provided valuable transcriptome data sets for future studies on depression.

overall_design: Neuron type specific transcriptome profiles in the NAc of mouse depression model (chronic social defeat stress) were generated using RiboTag and RNA sequencing methods (n=4~5)

first: Deveroux

last: Ferguson


status: Public on May 18 2021

city: Wuhan

first: Chao

last: Yang

state: Hubei

address: No. 99 ZhangZhiDong Street Wuchang District

department: Department of gastrointestinal surgery

country: China

institute: Remin Hospital of Wuhan University

type: Non-coding RNA profiling by high throughput sequencing

summary: Lymph node metastasis(LNM) is the most common metastatic pathway of colorectal cancer (CRC), with a rate of 40.5% to 49.7%. Meanwhile, LNM also is one of the most important prognostic risk factor and often predicts a poor clinical outcome. Therefore, it is necessary to identify relevant genes or elucidate potential molecular mechanisms of LNM in order to develop effective prevention and treatment strategies. The aim of this study is to give an insight into the specific signatures and molecular mechanisms of lymph node metastasis in CRC.

overall_design: Expression profiles for lymph node metastasis in I-III colorectal cancer patients was measured, including 4 LNM-positive cancer samples, 4 LNM-negative samples, and 2 adjacent normal samples. Furthermore, these 8 CRC samples contained 4 mismatch repair-deficient (dMMR) and 4 mismatch repair-proficient (pMMR) samples.

first: Shuoyang

last: Huang


title: Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19

status: Public on May 08 2021

city: Stanford

first: Aaron

middle: James

last: Wilk

state: California

address: 300 Pasteur Dr Bldg S131, Grant

institute: Stanford University

summary: Our understanding of protective vs. pathologic immune responses to SARS-CoV-2, the virus that causes Coronavirus disease 2019 (COVID-19), is limited by inadequate profiling of patients at the extremes of the disease severity spectrum. Here, we performed multi-omic single-cell immune profiling of 64 COVID-19 patients across the full range of disease severity, from outpatients with mild disease to fatal cases. Our transcriptomic, epigenomic, and proteomic analyses reveal widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, with the most profound disturbances including prominent hyperactivation signatures in neutrophils and monocytes with anti-inflammatory features. We also leverage epigenomic analysis to identify loss of accessibility at NF-kB binding sites within pro-inflammatory cytokine gene loci as a potential mechanism for the striking lack of cytokine production observed in monocytes in severe and fatal COVID-19. We further demonstrate that emergency myelopoiesis is a prominent feature of fatal COVID-19. Collectively, our results reveal disease severity-associated immune phenotypes in COVID-19 and identify pathogenesis-associated pathways that are potential targets for therapeutic intervention.

overall_design: Single-cell RNA and single-cell ATAC sequencing of peripheral blood mononuclear cells (PBMCs) from 8 samples from COVID-19 patients and 6 healthy controls.

first: Ben

last: Parks

first: William

last: Greenleaf

first: Catherine

last: Blish


title: Methylation studies in wild ass and Grevy's zebra

status: Public on Nov 25 2021

first: Steve

last: Horvath

summary:
An Infinium microarray platform (GPL28271, HorvathMammalMethylChip40) was used to generate DNA methylation data from blood samples in two equid species: Somali wild ass and Grevy's zebra.
n=12 blood samples

sample_organism:
Equus grevyi
Equus asinus somalicus

overall_design: Genome annotations of the array can be downloaded from https://github.com/shorvath/MammalianMethylationConsortium

first: Todd

last: Robeck


title: Methylation studies in naked mole rat. Part 1

summary:
An Infinium microarray platform (GPL28271, HorvathMammalMethylChip40) was used to generate DNA methylation data from many tissues of the naked mole rat
We generated DNA methylation data from n=289  tissues.  All tissues except for skin biopsies and blood were obtained from frozen tissue collection that were euthanized for other studies. Skin biopsies (2 mm punch) were collected from the backs of the animals under local anesthesia. Blood samples were collected from the tails. The n=3 induced pluripotent stem cells from NMR were generated as described in (Tan et al 2017., PMID: 29107597). As control set for the iPS study, we used n=3 fibroblasts samples. Genomic DNA was extracted using Qiagen DNeasy Blood and Tissue kit and quantified using Nanodrop and Qubit.als

overall_design:
N=289 DNA samples from 13 sources of DNA: adipose, blood, cerebellum, cerebral cortex,  fibroblast, heart,        induced pluripotent stem cells, kidney, liver, lung, muscle, skin, spleen. Genome annotations of the array can be downloaded from https://github.com/shorvath/MammalianMethylationConsortium
The characteristics: Queen pertains to female naked mole rats. Queen=yes indicates that the female is a breeding queen. Queen=no indicates that the animal is a non-breeding female. NA=not applicable (e.g. male) or unknown.
The characteristics: ConfidenceInAgeEstimate with numeric value between 0 and 100. It indicates the confidence in the accuracy in the age estimate. This value was assigned by the team of investigators. It is based on their subjective confidence in the accuracy of the record when it comes to the chronological age at the time of samle collection. A value of 100 was chosen for samples whose birthday and death date was accuratly kown. We only used samples with a confidence of 90 or higher when building or evaluating DNA methylation based age estimators or when conducting epigenome wide association studies of chronological age.
The characteristics: Age represents chronological/calendar age of the animal at the time of sample collection. Age is in units of years.

first: Vera

last: Gorbunova

first: Andrei

last: Seluanov


title: Nonlinear control of transcription through promoter-enhancer interactions [RNA-seq]

status: Public on Nov 05 2021

city: Basel

first: Luca

last: Giorgetti

address: Fabrikstrasse 24

institute: Friedrich Miescher Institute for Biomedical Research

summary: Chromosome structure in mammals is thought to regulate transcription by modulating spatial proximity between enhancers and promoters. However, the mechanisms by which this occurs remain elusive, and reports suggested moderate to no correlation between physical proximity and transcription. Whether and how chromosome structure is actually translated into transcriptional outputs thus remains unclear. Here we use a novel assay to position an enhancer at hundreds of different chromosomal sites relative to a fixed promoter and quantitatively measure promoter output.

overall_design: We identify active promoters in mouse embryonic stem cell by performing total RNA-seq in triplicates

first: Jessica

last: Zuin

first: Gregory

last: Roth

first: Yinxiu

last: Zhan

first: Julie

last: Cramard

first: Josef

last: Redolfi

first: Ewa

last: Piskadlo

first: Pia

last: Mach

first: Mariya

last: Kryzhanovska

first: Gergely

last: Tihanyi

first: Hubertus

last: Kohler

first: Peter

last: Meister

first: Sebastien

last: Smallwood

first: Giorgetti

last: Luca


title: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly-ADP-ribose polymerase (TIPARP/PARP7) catalytic mutant mice (TiparpH532A) have increased sensitivity to TCDD-induced hepatotoxicity and lethality

status: Public on Sep 08 2021

city: Oslo

first: Jason

last: Matthews

address: Sognsvannsveien 9

department: Nutrition

country: Norway

institute: University of Oslo

summary: We previously reported that TCDD-inducible poly-ADP-ribose polymerase (TIPARP), an aryl hydrocarbon receptor (AHR) target gene and mono-ADP-ribosyltransferase, acts as part of a negative feedback loop to repress AHR signalling, a process that prevented by a single H532A mutation that destroys TIPARP catalytic activity. Moreover, whole body or hepatocyte specific-deletion of, increases the sensitivity of mice to dioxin-induced toxicities. Based on these findings, we hypothesized that the loss of TIPARP catalytic activity would increase sensitivity to TCDD-induced toxicity in vivo. To test the hypothesis, we created a catalytically deficient mouse line (TiparpH532A) by introducing a single H532A mutation in Tiparp. Treatment of mouse embryonic fibroblasts (MEFs) or hepatocytes isolated from TiparpH532A mice confirmed the increased TCDD-induced expression of the AHR target genes, Cyp1a1, Cyp1b1 and Tiparp. We also confirmed TCDD-dependent increases in Tiparp protein levels, as well as increased protein stabilization of TiparpH532A compared Tiparp+/+ protein.  TiparpH532A mice given a single injection of 10 ug/kg dioxin, a non-lethal dose in Tiparp+/+ mice, did not survive beyond day 10. All Tiparp+/+ mice survived the 30-day treatment. Dioxin treated TiparpH532A mice displayed increased expression of Ahr target genes, increased steatohepatitis and hepatotoxicity as indicated by increased alanine aminotransferase activity compared with wildtypes. Taken together, these data further support TIPARP as a key negative regulator of AHR activity and its specific loss of its catalytic activity is sufficient to increase the sensitivity to dioxin-induced hepatosteatosis and lethality. TIPARP has recently emerged as a potential anti-cancer therapeutic; however, AHR signalling and toxicity will need to be carefully considered in determining the consequences of TIPARP inhibition.

overall_design: Hepatic mRNA profiles of Tiparp wild type (Tiparp+/+) and Tiparp catalytic mutant (TiparpH532A) mice, euthanized 6-days after treatment with a single IP dose of either corn oil or 10 ug/kg BW TCDD

first: David

last: Hutin

first: Alexandra

last: Long

first: Denis

last: Grant


title: Nicotinamide N-methyltransferase is related to MELF pattern invasion in endometrioid carcinoma

city: Suita

first: Daisuke

last: Okuzaki

state: Osaka

address: Yamadaoka 3-1

department: Immunology Frontier Research Center

institute: Osaka univ.


title: Methylation studies in plains zebras

first: Steve

last: Horvath

summary:
An Infinium microarray platform (GPL28271, HorvathMammalMethylChip40) was used to generate DNA methylation data from many tissues of plains zebras (Equus quagga).
Both whole blood (96) and remote biopsy (24) samples were obtained from a captive population of zebras maintained in a semi-wild state. After eliminating samples with low confidence for individual identity and age, we retained 76 blood samples and 20 biopsy samples, totaling 96 zebra samples.

overall_design: Genome annotations of the mammalian methylation array can be downloaded from https://github.com/shorvath/MammalianMethylationConsortium

first: Brenda

last: Larison


title: Enhanced efficacy of aurora kinase inhibitors in G2/M checkpoint deficient TP53 mutant uterine carcinomas is linked to the summation of LKB1-AKT-p53 interactions [RNA-seq]

city: Boston

first: Sarah

middle: J.

last: Hill

state: MA

address: 450 Brookline Ave., Dana Building, Room 1410C

department: Medical Oncology

institute: Dana-Farber Cancer Institute

summary: We report bulk RNA sequencing, low pass whole genome sequencing, and targeted exome sequencing data of six uterine cancer organoids and show how specific molecular defects in these organoids make them sensitive to cell cycle targeting therapies.

overall_design: Transcriptomic and genomic sequencing of uterine cancer organoids.

first: Aniket

last: Shetty

first: Ruiyang

last: He


title: Enhanced efficacy of aurora kinase inhibitors in G2/M checkpoint deficient TP53 mutant uterine carcinomas is linked to the summation of LKB1-AKT-p53 interactions [WGS]


title: Quantitative gene expression in gastrointestinal tissues following consistent activation of ChAT or TH enteric neurons versus non-activated control mice

status: Public on Aug 03 2021

city: PASADENA

first: Bryan

last: Yoo

address: 1200 E California Blvd, Mc 156-29

department: BBE

institute: California Institute of Technology

summary: Tools to study, and knowledge of, enteric nervous system development and function lag behind brain research. Herein, we deploy recombinant adeno-associated viral (rAAV) vectors with enhanced tropism for the gut to map and activate enteric neurons in mice with spatial and temporal resolution. we employed chemogentics to specifically activate gut neurons that express choline acetyltransferase (ChAT+) or tyrosine hydroxylase (TH+). Targeted activation of ChAT+ or TH+ neuronal populations associated with the gastrointestinal (GI) tract altered the intestinal transcriptome.

overall_design: ChAT-Cre or TH-Cre mice (6-8 weeks of age) were infected with activating DREADDs or a control peripheral nervous system virus expressing a reporter protein instead (AAV-PHP.S:hSYN1-DIO-mRuby2). C21 was administered intraperitoneally (i.p.), once daily for 10 consecutive days to all mice. One hour following the last C21 injection (when mice are 10-13 weeks of age), 1cm of tissue from the distal SI and proximal colon was harvested, and gene expression profiled by QuantSeq, a quantitative 3’ mRNA-sequencing technology.

middle: B

first: Jessica

last: Griffiths

first: Sarkis

last: Mazmanian


title: Nicotinamide N-methyltransferase is related to MELF pattern invasion in endometrioid carcinoma [RNA-seq_pico input]

summary: In endometrioid carcinoma (EC), grade 1 (G1) EC is generally associated with a good prognosis. However, in a minority of G1, we often find a more aggressive histological pattern: MELF (microcystic, elongated, and fragmented) pattern. We previously revealed that EC with high expression of S100A4 and serum deprivation-response protein (SDPR) was related to MELF pattern invasion. However, the molecular feature of the invasive front area of MELF pattern has not been investigated. In the current study, we searched for genes preferentially expressed in the invasive front area of EC with MELF pattern by using laser microdissection and RNA sequencing, and revealed that Nicotinamide N-methyltransferase (NNMT) is related to invasiveness of MELF pattern. We confirmed that NNMT expression was high in the invasive front area of MELF pattern in immunohistochemical analysis. Moreover, using endometrioid carcinoma cell lines, we showed that NNMT promotes migration, invasion, colony formation, epithelial-mesenchymal transition (EMT), and chemoresistance. We speculated that depletion of NNMT promotes histone methylation and leads to tumor suppression because NNMT consumes S-adenosyl methionine (SAM), which is an essential methylation cofactor. We showed that NNMT-knockout cells the expression of H3K9me2 was enhanced. We speculate that methylation of H3K9 lead to repress the transcription of various oncogenic genes by performing RNA sequencing using NNMT-knockout cell lines. Our findings showed the possibility that NNMT inhibitors, which are expected to be used for the treatment of metabolic disorders, is effective for the treatment of an aggressive EC. This is the first report of the gene analysis focused on the morphological changes of MELF pattern invasion of EC.

overall_design: We selected 2 cases from 30 cases of EC with MELF pattern invasion. To compare the levels of gene expression profiles between the invasive front area and the surface area, laser microdissection was performed using a Leica LMD 7000 (Leica Microsystems, Wetzlar, Germany).

first: Shinichiro

last: Tahara

first: Eiichi

last: Morii


title: Nonlinear control of transcription through promoter-enhancer interactions [splinkerette PCR]

status: Public on Apr 26 2021

first: Luca

last: Giorgetti

overall_design: We map enhancer reinsertion genome-wide by performing splinkerette PCR coupled with NGS sequencing

last: Zuin

first: Gregory

last: Roth

first: Yinxiu

last: Zhan

first: Julie

last: Cramard

first: Josef

last: Redolfi

first: Ewa

last: Piskadlo

first: Pia

last: Mach

first: Mariya

last: Kryzhanovska

first: Gergely

last: Tihanyi

first: Hubertus

last: Kohler

first: Peter

last: Meister

first: Sebastien

last: Smallwood


title: Estrogen Receptor Activation Time Course at 3, 6, 12 & 24h in MCF7, T47D and MDA-MB-231 with and without ZMIZ1 knockdown

status: Public on Apr 27 2021

city: York

first: Andrew

middle: Nicholas

last: Holding

address: Wentwork Way

department: Biology

country: United Kingdom

institute: University of York

summary: To establish the role of ZMIZ1 in the Estrogen Recptor complex we undertook an time course following estrogen stimulation with and without ZMIZ1 knockdown monitored by RNA-seq.

overall_design: ZMIZ1 was knocked down in two ER+ cell lines (MCF7 and  T47D) and in one ER negative cell line (MDA-MB-231) 24 hours before stimulating with estrogen. RNA-seq data was then collected for four isogenic replicates at 3h, 6h, 12h and 24h after stimulation with estrogen. siCTRL, RNAiMAX only and EtOH  controls were included.

first: Anze

last: Godicelj

first: Federico

last: Giorgi

first: Florian

last: Markowetz


title: Nonlinear control of transcription through promoter-enhancer interactions

last: Giorgetti

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

overall_design: Refer to individual Series


title: Beef cattle multi-tissue transcriptome

status: Public on May 05 2021

city: Hangzhou

first: Huizeng

last: Sun

state: Zhejiang

address: 866 Yuhangtang Road

department: College of Animal Sciences

institute: Zhejiang University

summary: The transcriptome of 189 samples across four tissues from 48 beef steers with varied feed efficiency were generated using Illumina HiSeq4000

overall_design: Totally 48 beef steers within 3 breeds from a large beef cattle cohort raised at Kinsella ranch, University of Alberta (Alberta, Canada) were used in this study.

first: Leluo

last: Guan


title: Reduced representation bisulfite sequencing in liver of rats exposed to glyphosate, MON 52276, and a mixture of pesticides

status: Public on Apr 12 2021

city: London

first: Robin

last: Mesnage

address: Guy's Hospital, 8th Floor, Tower Wing

institute: Kings College London

type: Methylation profiling by high throughput sequencing

summary: Human health effects from chronic exposure to pesticide residues are little investigated. We compared standard histopathology and serum biochemistry measures and multi-omics analyses in an in vivo subchronic toxicity test of a glyphosate, its formulated product MON 52276, and mixture of six pesticide active ingredients frequently detected in foodstuffs (azoxystrobin, boscalid, chlorpyrifos, glyphosate, imidacloprid and thiabendazole). Sprague-Dawley rats were administered with the pesticide mixture with each ingredient at its regulatory permitted acceptable daily intake.

overall_design: Evaluation of methylation profiles in liver of rats exposed to glyphosate, MON 52276, and a mixture of pesticides

first: Charles

last: Mein


title: Transcriptome changes during inducable gametocytogenesis in Plasmodium berghei parasites

status: Public on Mar 13 2021

city: Glasgow

first: Katarzyna

middle: Kinga

last: Modrzynska

state: Glasgow (City of)

address: B627 Sir Graeme Davies Building, 120 University Place

institute: Wellcome Trust Centre for Molecular Parasitology

summary: During the malaria infection, Plasmodium parasites invade the host’s red blood cells where they can differentiate into two different life forms. The majority will replicate asexually and infect new erythrocytes. A small percentage, however, will transform into gametocytes – a specialized sexual stage able to survive and develop when taken up by Anopheles mosquito. As the gametocytes ensure the parasite’s transmission to a new host, their generation is an attractive target for new antimalarial interventions. The molecular mechanisms controlling gametocytogenesis, however, remain largely unknown due to the technical challenges: the early gametocytes are morphologically indistinguishable from asexual parasites and present in very low numbers during the infection.     Recently, AP2-G  - a transcription factor from an apicomplexa-specific apiAP2 family – was described as indispensable for gametocyte commitment in both human malaria parasite Plasmodium falciparum and rodent malaria model Plasmodium berghei. Therefore, we have decided to test whether the overexpression of this factor alone could increase gametocyte production and enable the investigation of uncharacterised, earliest stages of gametocyte development. To this end, we have engineered PBGAMi  - a Plasmodium berghei line, in which all parasites were ap2-g deficient by default but able to overexpress it when induced with rapamycin. While the control parasites (PBGAMi R-), as expected, differentiated into asexual forms (schizonts) only, almost all rapamycin-treated parasites (PBGAMi R+) transformed into gametocytes. We used the generated line to perform RNA-seq analysis of the R- and R+ populations at different time points of their development and identify the changes arising between them, mapping the sequence of events leading to the formation of gametocytes. At the same time we have generated purified transcriptomes of male and female gametocytes for the reference

overall_design: A synchronised population of Plasmodium berghei PBGAMi parasites was either induced with rapamycin (which caused the ap2-g overexpression and gametocyte conversion) or allowed to develop asexually. Parasites from both groups were harvested at different time points post induction and RNA-seq was used to analyse their transcriptome. In parallel the gametocytes from the previously published line (expressesing RFP fluorescent marker  in females and GFP marker in males) (Ponzi et al.,2009) were FACS sorted, with ~5mln of cells form  each sex sorted into parasite media

last: Waters

first: Oliver

last: Billker


title: Nonlinear control of transcription through promoter-enhancer interactions [Nanopore]

first: Luca

overall_design: We performed capture oxford nanopore sequencing to confirm that the insertion of the transgene occurred in a single copy

first: Jessica

last: Zuin

first: Gregory

last: Roth

first: Yinxiu

last: Zhan

first: Julie

last: Cramard

first: Josef

last: Redolfi

first: Ewa

last: Piskadlo

last: Mach

last: Kryzhanovska

first: Giorgetti

last: Luca


title: Chip-Seq and RNA-Seq analysis on developing gamma-delta T cells

status: Public on Mar 10 2021

city: philadelphia

first: suraj

last: peri

state: PA

address: 333 cottman ave

department: biostatistics and bioinformatics

institute: Fox chase cancer center


title: Enhanced efficacy of aurora kinase inhibitors in G2/M checkpoint deficient TP53 mutant uterine carcinomas is linked to the summation of LKB1-AKT-p53 interactions [exome-seq]

first: Sarah

last: Hill

first: Aniket

last: Shetty

first: Ruiyang

last: He


title: Lysine Demethylase 6b (Kdm6b) is essential for proper generation of effector CD8+ T lymphocytes by inducing chromatin accessibility in effector-associated genes

status: Public on Feb 25 2021

city: North Chicago

first: Gustavo

middle: Javier

last: Martinez

state: United States

address: 3333 Green Bay Rd Department of Microbiology and Immunology

department: Center for Cancer Cell Biology, Immunology and Infection

institute: Rosalind Franklin University

summary: The transcriptional and epigenetic regulation of CD8+ T cell differentiation is critical for balancing pathogen eradication and long-term immunity by effector and memory CTLs. Here, we demonstrate that the Lysine Demethylase 6b (Kdm6b) is essential for the proper generation and function of effector CD8+ T cells during acute infection and tumor eradication. We found that cells lacking Kdm6b (either T cell-specific KO or knockdown utilizing shRNA strategies) show an enhanced generation of memory precursor and early effector cells upon acute viral infection in a cell-intrinsic manner. We also demonstrate that Kdm6b is indispensable for proper effector functions and tumor protection, and that memory CD8+ T cells lacking Kdm6b displayed a defective recall response. Mechanistically, we identified that Kdm6b, through induction of chromatin accessibility in key effector-associated gene loci, allows for the proper generation of effector CTLs. Our results pinpoint the essential function of Kdm6b in allowing chromatin accessibility in effector-associated genes, and identify Kdm6b as a potential target for therapeutics in diseases with dysregulated effector responses.

overall_design: WT or Kdm6b-deficient (either T cell-specific KO or knockdown using shRNA strategies) were FACS-sorted and RNA-seq and ATAC-seq performed. Experimental design and protocols are detailed in the corresponding publication.

first: Tianhao

last: Xu


title: Enhanced efficacy of aurora kinase inhibitors in G2/M checkpoint deficient TP53 mutant uterine carcinomas is linked to the summation of LKB1-AKT-p53 interactions

status: Public on May 07 2021


title: Chip-Seq analysis on developing gamma-delta T cells

summary: gd T cells are increasingly understood to play critical roles in host defense and can also contribute to immune mediated pathology; however, their origins remain poorly understood. There is growing evidence suggesting that immature bipotent progenitors in the thymus are instructed to adopt the ab and γδ fates, respectively, by differences in T cell receptor (TCR) signal strength or duration, with stronger and more prolonged signals directing adoption of the gd fate. These differences in TCR signaling instruct fate through graded induction of Id3, which in turn, produces graded reductions in the ability of E box DNA binding proteins (E proteins) to bind DNA. While E proteins play a central role in regulating lymphoid fate decisions, their downstream gene targets through which they specify fate have not been identified. Understanding how E proteins control gd lineage commitment requires a comprehensive, network-based approach. Consequently, we employed ChIP-Seq to identify the enhancers whose occupancy by E-proteins was altered by TCR signaling during gd lineage commitment and we identified their targets using a chromosome capture method termed Hi-C. These data were then integrated into a comprehensive, E-protein-focused, genome-wide network describing the genomic reorganization that occurs during gd lineage commitment. These studies revealed that E protein occupancy of enhancers was far more dramatically remodeled in progenitors adopting the gd lineage fate than in uncommitted progenitors exposed to the same selecting environment and has led to the identification of specific regulatory elements through which gd lineage commitment and effector function is controlled. One such element plays a critical role in controlling the expression of the transcription factor (TF) ThPOK, as well as the effector function of γδ T cells. Thus, our comprehensive approach has provided critical new insights into the molecular processes orchestrating gd lineage commitment and provides a framework for molecular dissection of both lineage commitment and effector function.

overall_design: Immature Rag2-deficient fetal liver progenitors were differentiated into DN3 thymocytes and isolated by flow cytometry. In addition the DN3 thymocytes were transduced with the KN6 gamma-delta T cell receptor and exposed to ligand-expressing OP9 monolayers to enable differentiation. After 3 days, progenitors that had not yet lost alpha-beta fate potential (CD73-) and those that had lost alpha-beta fate potential and committed to the gamma-delta fate (CD73+) were isolated by flow cytometry. These samples where then subjected to ChIP-Seq analysis with antibodies reactive with E2A and HEB proteins. Isolated genomic DNA was then sequenced. Duplicate samples were prepared.

first: David

middle: L

last: Wiest


title: Methylation clocks for age estimation in toothed whales and dolphins

city: Los Angeles

first: Steve

last: Horvath

address: 695 Charles E. Young Drive South, Box 708822

institute: University of California, Los Angeles

type: Methylation profiling by genome tiling array

summary:
An Infinium microarray platform (GPL28271, HorvathMammalMethylChip40) was used to generate DNA methylation data from several tissues (skin, blood) in toothed whales and dolphins.
Tissues: skin and blood.

sample_organism:
Delphinus delphis
Orcinus orca
Tursiops truncatus
Phocoena phocoena
Delphinapterus leucas
Globicephala macrorhynchus
Steno bredanensis
Cephalorhynchus commersonii
Sagmatias obliquidens

overall_design: N=545 tissue samples from 9 different toothed whale species were profiled on the mammalian methylation array platform (GPL28271). N= 238 skin tissue. The remaining samples come from blood (N=283), blubber (N=5), heart (2), kidney (2), liver (2), lung (2), lymphnode (2), muscle (2), pancreas (2), spleen (3), testis (1), thyroid (1). We profiled samples from the following 9 different toothed whale species whose Latin names are as follows: Cephalorhynchus commersonii (Commerson's dolphin), Delphinapterus leucas (Beluga), Delphinus delphis (Common dolphin), Globicephala macrorhynchus (Short-finned pilot whale), Lagenorhynchus obliquidens (Pacific white-sided dolphin), Orcinus orca (Killer whale), Phocoena phocoena (Harbor porpoise), Steno bredanensis (Rough-tooth dolphin), Tursiops truncatus (Bottlenose dolphin).  Genome annotations of the array can be downloaded from https://github.com/shorvath/MammalianMethylationConsortium

first: Todd

middle: R

last: Robeck


title: Epigenetic reprogramming rewires transcription during the alternation of generations in Arabidopsis

status: Public on Jan 26 2021

city: Tübingen

first: Michael

last: Borg

address: Max Planck Ring 5

department: Algal Development & Evolution

country: Germany

institute: Max Planck Insititue for Biology


title: RNA-Seq analysis on developing gamma-delta T cells

overall_design: Immature Rag2-deficient fetal liver progenitors were differentiated into DN3 thymocytes and isolated by flow cytometry. In addition the DN3 thymocytes were transduced with the KN6 gamma-delta T cell receptor and exposed to ligand-expressing OP9 monolayers to enable differentiation. After 3 days, progenitors that had not yet lost alpha-beta fate potential (CD73-) and those that had lost alpha-beta fate potential and committed to the gamma-delta fate (CD73+) were isolated by flow cytometry. Duplicate samples were lysed in Trizol. Total RNA was isolated and processed as previously described(Miyazaki et al., 2017).


title: Epigenetic reprogramming events rewire transcription during the alternation of generations in Arabidopsis [ATAC-Seq]

summary: Alternation between morphologically distinct haploid and diploid life forms is a defining feature of most plant and algal life cycles, yet the underlying molecular mechanisms that govern these transitions remain unclear. Here, we explore the dynamic relationship between chromatin accessibility and epigenetic modifications during life form transitions in Arabidopsis. The diploid-to-haploid life form transition is governed by the loss of H3K9me2 and DNA demethylation of transposon-associated cis-regulatory elements, which is associated with dramatic changes in chromatin accessibility and transcriptional reprogramming. In contrast, the global loss of H3K27me3 in the haploid form shapes a chromatin accessibility landscape that is poised to re-initiate the transition back to diploid life after fertilization. These distinct epigenetic reprogramming events rewire transcription through major reorganization of the regulatory epigenome to guide the alternation of generations in flowering plants.

overall_design: Genome-wide maps of chromatin accessilbity in developing Arabidopsis pollen


title: Cell competition as a barrier for interspecies chimerism between evolutionary distant species

status: Public on Dec 31 2020

city: shenzhen

first: CNSA

last: CNGB

address: BGI

institute: BGI

summary: we develop an interspecies pluripotent stem cell (PSC) co-culture strategy and uncover a previously unknown mode of cell competition. Interspecies PSC competition occurs during primed but not naive pluripotency, and between evolutionarily distant species. We identified genes related to NF-κB signaling pathways, among others, were upregulated in loser cells and genetic inactivation of RELA, a core component of canonical NF-κB pathway, could overcome interspecies PSC competition. We further showed that an upstream regulator of the NF-κB signaling, MYD88 innate immune signal transduction adaptor, was also involved in promoting loser PSC elimination. Suppressing interspecies PSC competition via genetic perturbation of MYD88 or P65 improved engraftment of human cells in early post-implantation mouse embryos. Our study discovers a new paradigm of cell competition and paves the way for studying evolutionarily conserved cell competition mechanisms during early mammalian development. Strategies developed here to overcome interspecies PSC competition may facilitate interspecies organogenesis between evolutionary distant species, including humans.

overall_design: Examination of 2 different mRNA expression level of human ESC cells in co-culture and separate culture condition

first: Canbin

last: Zheng

first: Yingying

last: Hu


title: Aortic gene expression profiles show how APOA-I levels modulate infammation, lysosomal activity and sphingolipid metabolism in murine atherosclerosis

status: Public on Dec 22 2020

city: Milan

first: Matteo

last: Chiara

address: via celoria 26

department: Biosciences

institute: University of Milan

summary:
HDL particles are known to possess several anti-atherogenic properties that include the removal of excess cholesterol from peripheral tissues, the maintenance of endothelial integrity, antioxidant and antiinflammatory activities. ApoA-I overexpression in apoE-deficient (EKO) mice has been shown to increase HDL levels and to strongly reduce atherosclerosis development. The aim of the study was to investigate gene expression patterns associated with atherosclerosis development in the aorta of EKO mice and how HDL plasma levels relate to gene expression patterns at different stages of atherosclerosis development and with different dietary treatments.
Methods Eight weeks old EKO mice, EKO mice overexpressing human apoA-I (EKO/hA-I) and wild-type mice as controls were fed either Chow or Western diet for 6 or 22 weeks. Cholesterol distribution among lipoproteins was evaluated and atherosclerosis of the aorta was quantified. High-throughput sequencing technologies were used to analyse the transcriptome of the aorta of the three genotypes in each experimental condition.
Results: In addition to the well-known activation of inflammation and immune response, the impairment of sphingolipid metabolism, phagosome-lysosome system and osteoclast differentiation emerged as relevant players in atherosclerosis development. The reduced atherosclerotic burden in the aorta of EKO mice expressing high levels of apoA-I was accompanied by a reduced activation of the immune system markers, as well as reduced perturbation of lysosomal activity and a better regulation of the sphingolipid synthesis pathway
Conclusions. ApoA-I modulates atherosclerosis development in the aorta of EKO mice affecting the expression of pathways additional to those associated with inflammation and immune response

overall_design: aortic mRNA profiles of 8-weeks old wild type (WT), APOE (EKO mice), and EKO mice overexpressing human apoA-I (EKO/hA-I) fed either Chow or Western diet for 6 or 22 weeks

first: Marco

last: Busnell

first: Stefano

last: Manzini

first: Alice

last: Colombo

first: Francesco

last: Potì

last: Horner

first: Giulia

last: Chiesa


title: Epigenetic reprogramming events rewire transcription during the alternation of generations in Arabidopsis [DNA methylation]

relation:
SubSeries of: GSE155369
Reanalysis of: GSM952446
Reanalysis of: GSM952447
Reanalysis of: GSM980986

overall_design:
Re-analysis of published pollen dme-2/+ DNA methylomes
third-party reanalysis
SRR516179, SRR516180, SRR534177
Adapter trimming was performed using TrimGalore version 0.6.2.
Reads were aligned to the Arabidopsis genome (TAIR10) using the Bismark  version 0.22.2
BAM files containing clonal deduplicated and uniquely mapped reads were then used as substrate for Methylpy software version 1.2.9
Bisulfite conversion rates were calculated using the unmethylated chloroplast genome. Differentially methylated regions (DMRs) were defined using Methylpy. Differentially methylated cytosines (DMCs) with coverage ≥4 overlapping reads were identified by root mean square tests and a false discovery rate ≤ 0.05.
Differentially methylated sites within 250 bp were collapsed into DMRs. DMRs were further filtered by discarding regions with < 5 DMCs.
TAIR10 cDNA sequences (Arabidopsis_thaliana.TAIR10.cdna.all.fa.gz)
*.DMC_fdr0.05.bed: Differentially methylated cystosines (DMCs) in dme-2/+ pollen compared to WT that pass the FDR threshold < 0.05
*.DMR.bed: Differentially methylated regions (DMRs) in dme-2/+ pollen compared to WT that pass the FDR threshold < 0.05

first: Ranjith

last: Papareddy


title: Nonlinear control of transcription through promoter-enhancer interactions [cHi-C]

first: Luca

last: Giorgetti

summary: Chromosome structure in mammals is thought to regulate transcription by modulating spatial proximity between enhancers and promoters. However, the mechanisms by which this occurs remain elusive, and reports suggested moderate to no correlation between physical proximity and transcription. Whether and how chromosome structure is actually translated into transcriptional outputs thus remains unclear. Here we use a novel assay to position an enhancer at hundreds of different chromosomal sites relative to a fixed promoter and quantitatively measure promoter output.

overall_design: We performed capture Hi-C experiments in different cell lines. ΔCTCF and ΔΔCTCF are used as control for the corresponding founder cell lines. The founder cell lines are used as control for the corresponding clones where the enhancer has jumped

first: Jessica

last: Zuin

first: Gregory

last: Roth

first: Yinxiu

last: Zhan

first: Julie

last: Cramard

first: Josef

last: Redolfi

first: Ewa

last: Piskadlo

first: Pia

last: Mach

first: Mariya

last: Kryzhanovska

first: Gergely

last: Tihanyi

first: Hubertus

last: Kohler

first: Peter

last: Meister

first: Sebastien

last: Smallwood

first: Giorgetti

last: Luca


title: An atlas of neural crest lineages along the posterior developing zebrafish at single-cell resolution

status: Public on Feb 16 2021

city: Houston

first: Rosa

last: Uribe

state: Texas

address: 6100 Main St.

department: BioSciences

institute: Rice University

summary: Neural crest cells (NCCs) are vertebrate stem cells that give rise to various cell types throughout the developing body in early life. Here, we utilized single-cell transcriptomic analyses to delineate NCC-derivatives along the posterior developing vertebrate, zebrafish, during the late embryonic to early larval stage, a period when NCCs are actively differentiating into distinct cellular lineages. We identified several major NCC/NCC-derived cell-types including mesenchyme, neural crest, neural, neuronal, glial, and pigment, from which we resolved over three dozen cellular subtypes. We dissected gene expression signatures of pigment progenitors delineating into chromatophore lineages, mesenchyme subtypes, and enteric NCCs transforming into enteric neurons. Global analysis of NCC derivatives revealed they were demarcated by combinatorial hox gene codes, with distinct profiles within neuronal cells. From these analyses, we present a comprehensive cell-type atlas that can be utilized as a valuable resource for further mechanistic and evolutionary investigations of NCC differentiation.

overall_design: To characterize the neural crest cell lineages present in the posterior zebrafish during the embryonic to larval transition (48-72 hours post fertilization) we utilized single-cell RNA sequencing (scRNA-Seq) on the 10x Genomics Chromium platform to build a dataset from GFP+ cells collected from sox10:GFP embryos.

first: Aubrey

middle: A

last: Howard

first: Phillip

last: Baker

first: Rodrigo

last: Ibarra-Garcia-Padilla

first: Joshua

last: Moore

first: Lucia

middle: J

last: Rivas

first: Eileen

last: Singleton

first: Jessa

last: Westheimer

first: Julia

last: Corteguera

first: James

last: Tallman


title: Expression profiling by high throughput sequencing for human induced pluripotent stem cells (iPSCs) derived astrocytes

status: Public on Jan 12 2021

city: Bergen

first: Kristina Xiao

last: Liang

state: Hordaland

address: Jonas Lies vei 87, P. O. Box 7804

institute: University of Bergen

summary: The pupose of this study is to explore thel transcriptome profiling of the astrocytes differentiated from POLG patient iPSCs comparing to the astrocyte generated from health control iPSCs or ESCs.

overall_design:
Examination of mRNA profile in iPSC-derived astrocytes.
Note from submitter: Human raw sequencing data (e.g.FASTQ) cannot be made publicly available due to their sensitive nature, as dictated by Norwegian law. This data can be made available on the basis of reasonable request and following permission from our Regional Ethics Committee (REC).

first: Kristina

middle: X


title: Transcriptome and methylome analysis reveal three cellular origins of pituitary tumors

status: Public on Nov 16 2020

city: México City

first: Daniel

last: Marrero-Rodriguez

state: México City

address: Av. Cuauhtémoc 330, Col. Doctores

department: Unidad de Investigacion Medica en Enfermedades Endocrinas

country: Mexico

institute: Instituto Mexicano del Seguro Social

summary:
The pituitary tumors (PA) arise in adenohypophyseal cells and are the second most common tumor in central nervous system. Reflective of their monoclonal cell of origin these tumors could be classified according to the hormone that they produce. The mutational and copy number variation burden in these tumors are scarce, indicating other molecular events are involved in pituitary tumorigenesis. Here we show throughout transcriptome and methylome analysis that there are three readily distinctive molecular signatures. The first group is comprised by the gonadotropes, null cell and silent corticotroph PA, the second group comprised by ACTH PA and the group cluster together the TSH-, PRL- and GH- PA. These groups showed CACNA2D4, EPHA4 and SLIT1 gene up-regulation, respectively. Pathway enrichment analysis support the previous observations. The calcium signaling pathway is characteristic for gonadotropes null cell and silent corticotroph, the Renin-Angiotensin system for the ACTH PA and the Fatty acid metabolisms for the TSH-, PRL-, GH- cluster. The analysis of scRNA-seq from non-tumoral pituitary tissue revealed that these three groups originate since the pituitary development/embryogenesis. The immune cell infiltration landscape revealed that PA could be potentially infiltrated by NK and mast cells. Taken together these results correlate with the expression of the NR5A1, TBX19 and POU1F1 transcription factors, which drive pituitary embryogenesis and theoretically tumorigenesis and potentially indicates three divergent cell precursors cells.
We used microarrays to detail the molecular alteration in PA compared to non-tumoral gland.

overall_design: CNFPA, ACTH-, GH-, PRL-, and TSH- adenomas were compared against non-tumoral pituitary gland.

first: Moises

last: Mercado-Atri

first: Keiko

last: Taniguchi-Ponciano


title: Multi-modal single cell analysis reveals gut microbiota reshapes brain immune landscape in aged mouse model.

status: Public on Nov 03 2020

city: Dallas

first: Siyuan

last: Zhang

address: 6001 Forest Park Rd

department: Department of Pathology

institute: UT Southwestern Medical Center

summary: We used 16S V3/V4 region amplification to evaluate the composition of bacteria species in mouse fecal pellets. Fecel pellets were collected from young-adult (12 weeks old) wild type C57Bl/6 mice and aged (72 weeks old) wild type C57Bl/6 mice after 21 days of vehicle or antibiotics treatment (to induce gut microbiota depletion). In one sequencing round, we sequenced a total of 12 different fecal samples (3 young control, 3 aged control, 3 young depleted gut microbiota (ABX) and 3 aged depleted gut microbiota (ABX)). Amplicons were indexed using the Nextera XT Index Kit and pooled into a library for Illumina sequencing.

overall_design: Fecal pellets were obtained from six 12 week old female C57Bl/6 mice and six 72 week old female C57Bl/6 mice . Three young-adult and three aged mice received vehicle treatment and had an unperturbed gut microbiota and three young-adult and three aged mice received antibiotics treatment and had a depleted gut microbiota. All 12 fecal pellet samples (3 from each group) were individually processed to extract DNA using the ZymoBIOMICS DNA Miniprep Kit.  Following DNA extraction, the V3/V4 regions of the 16S rRNA gene were amplified. Amplicons were indexed using the Nextera XT Index Kit. The libraries were normalized and multiplexed into a single pool prior to validation by Qubit High-Sensitivity dsDNA, Agilent Bioanalyzer DNA 7500 Chip, and Kapa Illumina Library Quantification qPCR analyses. The final library (8.5pM) and PhiX (0.7pM) were sequenced on the MiSeq System using MiSeq V2 500 cycle kit (250-PE with 8-bp dual indexing). Base calling and demultiplexing were performed by MiSeq Controller Software.

first: Samantha

last: Golomb


title: Biomarkers of Environmental Enteropathy in Children (BEECH) transcriptomic analysis

status: Public on Dec 04 2020

first: Paul

last: Kelly

state: UK

address: Turner Street

department: Immunobiology

institute: Blizard Institute Barts & The London School of Medicine

summary: The BEECH study enrolled 297 children with stunting or wasting in Misisi, Lusaka. This is a sub-study of n=30 RNAseq datasets from intestinal biopsies from children undergoing endoscopy who had failed to respond to a nutritional intervention

overall_design: Cross-sectional study of RNAseq data. With one exception, two biopsies from each child were individually sequenced.

first: Beatrice

last: Amadi


title: Epigenetic reprogramming events rewire transcription during the alternation of generations in Arabidopsis [Small RNA-Seq]

first: Michael

last: Borg

summary: Alternation between morphologically distinct haploid and diploid life forms is a defining feature of most plant and algal life cycles, yet the underlying molecular mechanisms that govern these transitions remain unclear. Here, we explore the dynamic relationship between chromatin accessibility and epigenetic modifications during life form transitions in Arabidopsis. The diploid-to-haploid life form transition is governed by the loss of H3K9me2 and DNA demethylation of transposon-associated cis-regulatory elements. This event is associated with dramatic changes in chromatin accessibility and transcriptional reprogramming. In contrast, the global loss of H3K27me3 in the haploid form shapes a chromatin accessibility landscape that is poised to re-initiate the transition back to diploid life after fertilization. Hence, distinct epigenetic reprogramming events rewire transcription through major reorganization of the regulatory epigenome to guide the alternation of generations in flowering plants.

relation:
SubSeries of: GSE155369
Reanalysis of: GSM1495677
Reanalysis of: GSM1495679
Reanalysis of: GSM2829912
Reanalysis of: GSM4630744
Reanalysis of: GSM4630745
Reanalysis of: GSM4630746

overall_design:
Re-analysis of published pollen small RNA-seq [SRR1567670, SRR1567672,SRR6208912,SRR12067243,SRR12067244,SRR12067245]
Adapter trimming was performed using cutadapt version 1.9.
Reads were aligned to the Arabidopsis genome (TAIR10) using the STAR  version 2.7 requiring zero mismatches and ≤ 100 multiple end-to-end alignments
The resulting SAM files were used as input for readmapIO.py software (Schon et al., 2018) to reassign multimappers with a “rich-get-richer” algorithm.
The output bedFiles were sorted, condensed and normalized for total genome matching reads.
TAIR10 cDNA sequences (Arabidopsis_thaliana.TAIR10.cdna.all.fa.gz)
*.bed: BED files of small RNAs

first: Ranjith

middle: K

last: Papareddy


title: RUNX1 overexpression in precursor B acute leukemia cells

status: Public on Oct 30 2020

city: Kuopio

first: Merja

last: Heinäniemi

address: Yliopistonranta 1 E

department: School of Medicine

country: Finland

institute: University of Eastern Finland

summary: Overexpression of the transcription factor RUNX1 was studied in Nalm-6 precursor B acute lymphoblastic leukemia cells. The active enhancer histone marker H3K27ac and RUNX1 were measured using ChIP-seq. The effect on gene expression was analyzed using single cell RNA-sequencing.

overall_design:
ChIP-seq profiles were generated from Nalm-6 pre-B-ALL cell line after induced wt RUNX1 or empty vector expression for 48 h. Empty vector induction cell line was used as controls. Mnase digestion was used for DNA fragmentation. Antibodies against H3K27ac and RUNX1 compared to input.
scRNA-seq samples were generated from 72 h after induction using the 10X Genomics Chromium platform.

first: Juha

last: Mehtonen

first: Susanna

last: Teppo

first: Mari

last: Lahnalampi

first: Olli

last: Lohi


title: Global RNA expression profiling of k13-edited mutant and isogenic wild-type Plasmodium falciparum malaria parasites during the parasite's intra-erythrocytic developmental cycle and the parasite's response to dihydroartemisinin (DHA).

status: Public on Nov 01 2020

city: Singapore

first: Sachel

last: Mok

address: 60 Nanyang Drive

country: Singapore

institute: Nanyang Technological University

summary: K13 mutations are causal for artemisinin resistance in Plasmodium falciparum human malaria. The objective of our study is to characterize gene expression signatures associated with K13 mutations by comparing transcriptional profiles and response to DHA of K13 mutant (C580Y, R539T) and isogenic wild-type lines that were generated by zinc finger nuclease (ZFN) based editing in a long-term adapted (Dd2) and a contemporary laboratory-adapted clinical isolate (Cam3.II).

overall_design: We employed microarray technology to establish the global gene expression profiles of these five parasite lines (Dd2 K13 WT, Dd2 K13 R539T, Dd2 K13 C580Y, Cam3.II K13 R539T, Cam3.II K13 WT) from early ring to late schizont stage over the 48h intra-erythrocytic developmental cycle. Samples were collected at 0, 3, 6, 16, 24, 32, 48h time points for Dd2 lines and 0, 8, 16, 24, 32, 40, 48h for Cam3.II lines. The RNA expression profiles of the K13 mutant and isogenic wild type parasites were compared to identify changes at basal levels. Parasites were also treated with either 700nM dihydroartemisinin (DHA) or 0.1% DMSO vehicle for 6h and sampled at 3, 6, 24, 32 and 48h post-treatment to identify differences in transcriptional response to DHA associated with K13 mutations. Three independent experiments were performed for each parasite strain and condition, except for Cam3.II DHA treatment which was only done once. Extraction of total RNA, synthesis and amplification of target DNA was carried out as described (in Z. Bozdech, S. Mok & A. P. Gupta (2013) DNA microarray-based genome-wide analyses of Plasmodium parasites. Methods in molecular biology 923: 189-211). Cy5-labelled cDNA samples were hybridized against a common Cy3-labelled pool consisting of RNA from mixed 3D7 asexual stages on a custom microarray platform.

first: David

last: Fidock

first: Zbynek

last: Bozdech


title: RNAseq analysis comparing gene expression in Drosophila Gpdh1 mutant and Gpdh1; Ldh double mutants vs control strains

status: Public on Oct 25 2020

city: Bloomington

first: Jason

last: Tennessen

state: IN

address: 1001 E. Third St

department: Department of Biology

institute: Indiana University

summary: The goal of this study was to determine how loss of Gpdh1 or both Gpdh1 and Ldh influences gene expression in Drosophila larvae. RNA was isolated from Drosopohila Gpdh1 single mutants, Gpdh1; Ldh double mutants, as well as control larvae that were heterozygous for either the Gpdh1 mutations or both Gpdh1 and Ldh mutations.

overall_design: Larvae were collected as described in Li, H., Tennessen, J. M. Preparation of Drosophila Larval Samples for Gas Chromatography-Mass Spectrometry (GC-MS)-based Metabolomics. J. Vis. Exp. (136), e57847, doi:10.3791/57847 (2018). RNA was purified from staged mid-L3 larvae using a RNeasy Mini Kit (Qiagen). Sequencing was performed using an Illumina NextSeq500 platform with 75 bp sequencing module generating 41 bp paired-end reads. After the sequencing run, demultiplexing was performed with bcl2fastq v2.20.0.422.

first: Hongde

last: Li


title: Epigenetic reprogramming events rewire transcription during the alternation of generations in Arabidopsis [RNA-Seq]

overall_design: Gene expression profiling of VN and dme-2/+ mutant pollen.


title: Hairy Cell Leukemia Cell Line JOK1 +/- RhoH Reconstitution

status: Public on Jan 03 2021

city: lille

first: frédéric

last: leprêtre

address: Boulevard du Pr Leclercq

department: CHU of Lille, CBP

country: France

institute: Lille University

summary:
The hairy cell leukemia line JOK1 with low RhoH expression was stably trasfected with either an empty expression vector or this same vector expressing human RhoH. The transcriptomes of these two daughter lines were then compared by differential microarray analysis
The hairy cell leukemia line JOK1 with low RhoH expression was stably trasfected with either an empty expression vector or this same vector expressing human RhoH. The transcriptomes of these two daughter lines were then compared by differential microarray analysis

overall_design: Differential microarray analysis of the hairy cell leukemia cell line JOK1 +/- RhoH reconstitution

first: Carl

middle: S

last: Shelley

first: Sylvie

last: Galiègue-Zouitina


title: Genome Methylation Predicts Age and Longevity of Bats

status: Public on Jan 28 2021

first: Steve

last: Horvath

state: CA

department: Human Genetics

summary:
An Infinium microarray platform (GPL28271, HorvathMammalMethylChip40) was used to generate DNA methylation data from several tissues in several bat species.
Tissues: skin (wing punches), liver, brain, skeletal muscle.

sample_organism:
Pteropus poliocephalus
Pteropus hypomelanus
Rousettus aegyptiacus
Artibeus jamaicensis
Phyllostomus hastatus
Desmodus rotundus
Tadarida brasiliensis
Antrozous pallidus
Molossus molossus
Nycticeius humeralis
Eptesicus fuscus
Carollia perspicillata
Myotis myotis
Nyctalus noctula
Cynopterus brachyotis
Myotis lucifugus
Rhinolophus ferrumequinum
Saccopteryx bilineata
Eidolon helvum
Pteropus rodricensis
Phyllostomus discolor
Myotis brandtii
Pteropus vampyrus
Pteropus pumilus
Myotis vivesi
Rhynchonycteris naso
Leptonycteris yerbabuenae

overall_design:
N=860 tissue samples from 28 different bat species were profiled on the mammalian methylation array platform (GPL28271). N=796 of these samples come from wing punches (skin tissue). The remaining samples come from brain (N=9), liver (N=17), muscle (N=17). Due to quality issues N=28 samples were omitted from the analysis, see the characteristic variable CanBeUsedForAgingStudies. We profiled samples from 28 different bat species whose Latin names are as follows: Antrozouspallidus, Artibeusjamaicensis, Carolliaperspicillata, Cynopterusbrachyotis, Desmodusrotundus, Eidolonhelvum, Eptesicusfuscus, Leptonycterisyerbabuenae, Molossusmolossus, Myotisbrandtii, Myotislucifugus, Myotismyotis, Myotisvivesi, Nyctalusnoctula, Nycticeiushumeralis, Phyllostomusdiscolor, Phyllostomushastatus, Pteropusgiganteus, Pteropushypomelanus, Pteropuspoliocephalus, Pteropuspumilus, Pteropusrodricensis, Pteropusvampyrus, Rhinolophusferrumequinum, Rhynchonycterisnaso, Rousettusaegyptiacus, Saccopteryxbilineata, Tadaridabrasiliensis. Gene annotations for the microarray for ten bat genomes are available from the Digital Repository at the University of Maryland (DRUM) at http://hdl.handle.net/1903/26373 .
N=48 wing punch samples from different bat species were profiled on the mammalian methylation array platform (GPL28271). We profiled samples from different bat species whose Latin names are as follows:  Eptesicus fuscus, Phyllostomus hastatus, Carollia perspicillata. Gene annotations for the microarray for ten bat genomes are available from the Digital Repository at the University of Maryland (DRUM) at http://hdl.handle.net/1903/26373 .

first: Gerald

last: Wilkinson


title: NIH 3T3: Ctrl vs Reo

status: Public on Oct 07 2020

city: Edmonton

first: Maya

last: Shmulevitz

state: AB

country: Canada

institute: University of Alberta

summary: Transcriptional profiling of NIH 3T3 comparing WT, RIG-I KD with and without reovirus infection

overall_design: Samples: 2 uninfected, 2 reo infected, 1 shRIG-I


title: LSD1/KDM1A Maintains Genome-wide Homeostasis of Transcriptional Enhancers [ChIP-Seq]

status: Public on Sep 01 2020

city: Ann Arbor

first: Shigeki

last: Iwase

address: 1241 E. Catherine St.

institute: University of Michigan

summary: We performed ChIP-Seq in Lsd1-WT, Lsd1-GT and Kdm5c-WT mouse embryonic stem cells (mES).

overall_design: We performed ChIP-Seq of respective histone modifications and proteins in mES cells in technical duplicates. mES were crosslinked on plates with 1% Formaldehyde at 37C for 30 min. ChIP was performed according to PMID: 12808131 with minor modifications. Libraries were prepared according to Illumina's TruSeq protocol with minor modifications.

first: Saurabh

last: Agarwal


title: Immune and Metabolic Pathogenesis of Environmental Enteric Dysfunction in Childhood Undernutrition: A Birth Inception Cohort

status: Public on Oct 15 2020

city: Cincinnati

first: Yael

last: Haberman

state: OH

address: 3333 Burnet Ave

department: Gastroenterology

institute: Cincinnati Children's Hospital

summary: Background: Environmental enteric dysfunction (EED) is a major impediment to the Sustainable Development Goals of improved childhood survival and healthy growth worldwide. Few studies have longitudinally and endoscopically examined EED in children, limiting the development of effective interventions.   Methods: The Study of Environmental Enteropathy and Malnutrition (SEEM, Pakistan) followed 416 at-risk children prospectively from birth to 24 months of age in a rural district of Pakistan with a high prevalence of undernutrition. The duodenal genome-wide methylome and transcriptome was determined in 52 undernourished SEEM participants refractory to nutritional interventions and 42 North American pediatric controls and coeliac disease patients. Biomarkers were measured at 9 months and tested for association with growth at 24 months.   Findings: The EED core transcriptome exhibited suppression of genes regulating antioxidant and detoxification functions and lipid metabolism, and induction of genes encoding anti-microbial responses, interferon signaling, and lymphocyte activation. Relative to coeliac disease, suppression of genes encoding antioxidant and detoxification functions and induction of anti-microbial responses were EED-specific. At the epigenetic level, EED was notable for hyper-methylation of genes involved in epithelial metabolism and barrier function, and hypo-methylation of genes involved in immune responses and cell proliferation. Duodenal co-expression modules revealed associations between genes regulating lymphocyte proliferation and epithelial metabolism with histologic severity, faecal energy loss, and wasting (weight-for-height Z<-2.0), with data supporting epigenetic regulation. Immune response genes were attenuated by Giardia colonization.  After accounting for growth at study entry, IGF-1 and ferritin predicted linear growth, whereas leptin correlated with expression of epithelial carbohydrate metabolism and stem cell renewal genes, and weight gain.  Interpretation: Data suggest immune and metabolic pathways which may inform more effective interventions to improve outcomes in EED.  A validated model may be used to identify infants at greatest risk for future poor growth.

overall_design: Sample groups include 52 children with Environmental Enteric Dysfunction (EED), 17 with Celiac Disease, and 25 with no known gastrointestinal disorder (control).  1 patient from the control did not consent to data sharing and is not included in GEO.  All samples are from duodenal biopsies.  The patients with EED were recruited in Pakistan, all other patients were recruited in the United States (Ohio)

first: Najeeha

last: Iqbal

first: Sudhir

last: Ghandikota

first: Indika

last: Mallawaarachchi

first: Tzipi

last: Braun

first: Phillip

last: Dexheimer

first: Najeeb

last: Rahman

first: Rotem

last: Hadar

first: Kamran

last: Sadiq

first: Zubair

last: Ahmad

first: Romana

last: Idress

first: Junaid

first: Sheraz

last: Ahmed

first: Aneeta

last: Hotwani

first: Fayyaz

last: Umrani

first: Lubaina

last: Ehsan

first: Greg

last: Medlock

first: Chris

last: Moskaluk

first: Sana

last: Syed

first: Jennie

middle: Z

last: Ma

first: Anil

middle: G

last: Jegga

first: Sean

last: Moore

first: Syed

last: Ali

first: Lee

last: Denson


title: LSD1/KDM1A Maintains Genome-wide Homeostasis of Transcriptional Enhancers

first: Shigeki

last: Iwase

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

overall_design: Refer to individual Series


title: Genome-Wide Profiling of DNA Methylation and Gene Expression Identifies Candidate Genes for Human Diabetic Neuropathy (RRBS)

status: Public on Aug 24 2020

city: Grand Forks

first: Junguk

last: Hur

state: ND

address: 1301 N. Columbia Rd. Stop 9037

department: Biomedical Sciences

institute: University of North Dakota

summary: We perfomed transcriptomic and methylomic analysis of sural nerve biopsies from type 2 diabetic patients with neuropathy. Sural nerve transcriptomic and methylomic profiles were integrated and subsequent biological meaning investigated using KEGG pathway analysis of overlapping differentially expressed genes (DEGs) and differentially methylated genes (DMGs). A gene interation network was also generated including DEGs and DMGs, and common biological pathways were identified.

overall_design: RNA/DNA were extracted from human sural nerves of type 2 diabetic patients with neuropathy and sequenced. Samples were initially grouped based on changes in myelinated fiber density (dMFD) over 52 weeks, representing nerve regeneration and degeneration and divided into three groups (regenerators with high nerve regeneration, degenerator with high nerve degeneration, and intermediate for all others) as described in a previous publication by our group (PMID: 24101696). However, unbiased clustering of the expression data in this study identifed three distinct groups, which were significantly different in terms of HbA1c levels (Group1: 8.66 +/- 1.59; Group2: 7.77 +/- 1.43; Group3: 8.67 +/- 1.44). Reduced representation bisulfate sequencing (RRBS) were also performed on the same sural nerve biopsies, belonging to Group1 and Group2.

first: Kai

last: Guo

first: Eva

last: Feldman


title: LSD1/KDM1A Maintains Genome-wide Homeostasis of Transcriptional Enhancers [GRO-Seq]

summary: We performed GRO-Seq in Lsd1-WT and Lsd1-GT mouse embryonic stem cells (mES).SMCX_WT (KDM5c_WT) and SMCX_KO (KDM5c_KO) represent two additional mES cell lines used in the GRO-Seq study.

overall_design: We performed GRO run on mES cells in technical duplicates. Nuclei isolation and GRO was conducted as described in PMID:19056941 and PMID:21572438 with minor modifications. In addition to the presence of 0.2% IGEPAL CA-630, GRO on Kdm5c mES and Lsd1 mES were done in presence of 0.5% and 0.25% N-Lauroylsarcosine, respectively for 8 min at 30 degrees C.

first: Saurabh

last: Agarwal


title: LSD1/KDM1A Maintains Genome-wide Homeostasis of Transcriptional Enhancers [BrU-Seq]

summary: We performed BrU-Seq after shRNA mediated depletion of Lsd1 in primary cultures of mouse cortical neurons.

overall_design: Primary culture of CN were treated with 2 different Lsd1 shRNAs on 7 days in vitro in technical duplicates. 4 days later, the neurons were incubated with 2mM 5-Bromouridine for 32 min. Total RNA was isolated and BrU containing transcripts were enriched with anti-BrdU beads.


title: Wee1 inhibition in acute lymphoblastic leukemia with MLL rearrangement.

first: Merja

last: Heinäniemi

summary: Enhancer activity and RUNX1 binding was studied using ChIP-seq in mixed lineage leukemia t(4;11) rearranged acute lymphoblastic leukemia upon inhibition of the WEE1 kinase.

overall_design: ChIP-seq profiles were generated from RS4;11 cell line carrying the MLL rearrangment t(4;11) after 24 h WEE1 inhibition by AZD1775.  DMSO treated cells were used as controls. Brief sonication followed by Mnase digestion was used for DNA fragmentation. ChIP lysates were prepared with antibodies against H3K27ac and RUNX1 and compared to input.

first: Alena

last: Malyukova

first: Mari

last: Lahnalampi

first: Petri

last: Pölönen

first: Juha

last: Mehtonen

first: Olle

last: Sangfelt


title: AD-BXD [Ntg dataset 2]

status: Public on Aug 17 2020

city: Bar Harbor

first: Catherine

middle: C

last: Kaczorowski

state: ME

address: 600 Main Street

institute: The Jackson Laboratory

summary: Cg.5XFAD females (MMRRC Stock No #34848-JAX) were bred to males from BXD strains. The resulting F1 progeny were monitored throughout their lifepan to evaluate the effect of genetic background on cognitive and pathological traits. Samples here come from various Ntg-BXD lines at either 6 or 14 months of age. An earlier dataset of similar design (plus Non-transgenic littermates) was deposited as GSE101144. AD littermates of mice sampled here will be deposited as a separate GEO series.

overall_design: 71 Ntg samples. For final by-strain analysis, samples were averaged into strain/age/genotype/sex groups (For example, all D2 6mo 5XFAD males were averaged for final by-strain analysis)

first: Sarah

last: Neuner

first: Matthew

last: Huentelman


title: Molecular Transducers of Human Skeletal Muscle Remodeling under Different Loading States [CDF: Muscle_genome-build-id_ENST_binary]

status: Public on Aug 11 2020

city: Stirling

first: James

last: Timmons

address: Bridge of Allan

institute: Augur Precision Medicine LTD

summary:
The annotation of the Affymetrix HTA 2.0 array was updated to optimise the detection of RNA in human skeletal muscle biopsy samples by removing invalid and low signal-high-variance probes (as for CDF GPL24047). The probes were then summarized into groups (probe-sets) reflecting either an ensembl full transcript identifier (FL-ENST, GPL24047) or just the probes targeting the 3' UTR or the 5' UTR of that particular ENST.  Therefore, 3 different CDF were used to process the HTA 2.0 arrays in this study. Note that each CEL file was GC adjusted using APT while our custom CDF pipeline removes any probe that has >80% or <20% GC content (~50,000). The analysis was carried out only on the pairs of probe-sets i.e. FL-ENST vs 3'UTR or FL-ENST vs 5'UTR or 3'UTR vs 5'UTR.
Dynamic muscle loading alters tissue phenotype reflecting altered metabolic and functional demands. In humans, heterogeneous adaptation to loading complicates identification of the underpinning molecular regulators. We present a within-person analysis strategy that reduced heterogeneity for changes in muscle mass by ~40% and employed a genome-wide transcriptome method that modeled each mRNA from coding exons and 3’/5’ untranslated (UTR) regions. Our strategy detected ~3-4 times more regulated genes than similarly sized studies, including substantial UTR-selective regulation that other methods would not detect. We discovered a core of 141 genes correlated to muscle growth validated from newly analyzed independent samples (n=100). Further validating these identified genes, via RNAi in primary muscle cells, we demonstrate that members of the core genes were regulators of protein synthesis e.g. Molecular Transducers of Physical Activity in Humans MoTrPAC. Employing proteome-constrained networks and pathway analysis revealed notable relationships with the molecular characteristics of human muscle aging and insulin sensitivity, as well as potential drug-therapies. https://doi.org/10.1016/j.celrep.2020.107980

overall_design: human muscle profiles from men and women before and after muscle resistance training and/or unloading

first: Stuart

middle: M

last: Phillips


title: Genome-Wide Profiling of DNA Methylation and Gene Expression Identifies Candidate Genes for Human Diabetic Neuropathy (RNA-Seq)


title: Single cell profiling shows that murine forebrain neural stem cells reacquire a developing precursor state when activated to make adult-born neurons

status: Public on Jul 10 2020

city: Toronto

first: Freda

last: Miller

state: ON

address: 686 Bay Street

institute: Hospital for Sick Children

summary: In this study, we have utilized a single-cell RNA-Sequencing platform coupled with transgenic lineage tracing in order to follow the progression of different embryonic neural stem cell populations as they progress into adult dormant neural stem cells. We show that adult dormant V-SVZ neural stem cells of different embryonic origins share a common molecular signature and reacquire an embryonic precursor-like state when activated to make new neurons in the adult brain.

overall_design: High-throughput single cell transcriptomic profiles of the E14 cortex + GE tissue (3 replicates), E17 V-SVZ, P2 V-SVZ, P6 V-SVZ (3 replicates), P7 V-SVZ, P20 V-SVZ, P34 V-SVZ and P61 V-SVZ using either Emx1Cre or Nkx2.1Cre transgenic C57BL/6J mice were generated by single cell RNA sequencing, using the 10X Genomics platform. Processed and raw data for 12 datasets are included as indicated.

first: Michael

last: Borrett

first: Brendan

middle: T

last: Innes

first: Danielle

last: Jeong

first: Nareh

last: Tahmasian

first: Mekayla

last: Storer

first: Gary

middle: D

last: Bader

first: David

last: Kaplan


status: Public on Aug 01 2020

city: Qingdao

first: Yong

last: Zhao

state: Shandong

address: 700 Changcheng Road

department: College of Life Sciences

institute: Qingdao Agricultural University

summary: The goal of this study was designed to search for the important genes contribution to fertility. Single-cell RNA-seq of the goat oocytes samples from high fertility group (>three babys per birth) and low fertility group (< two babys per birth). And each group was divided into three subgroup based in the size of follicles: large, medium, and small follicles.

first: Yishan

last: Gao

first: Lingjiang

last: Min


title: DNA methylation profiles from a mouse model of Huntington's disease

status: Public on Jul 02 2020

city: Los Angeles

first: Steve

last: Horvath

address: 695 Charles E. Young Drive South, Box 708822

institute: University of California, Los Angeles

summary:
An Infinium microarray platform (HorvathMammalMethylChip40) was used to generate DNA methylation data from mouse tissues of a heterozygous Huntingtin expansion knock-in (Q175) and wildtype (WT) controls.
Mouse tissues: blood, liver, brain cortex, brain cerebellum, and striatum.

overall_design:
Mouse strain: C57B/l6J. Two genotypes: Q175 (Htt knockin) and WT control. Mice were sacrificed at age 6 months. Roughly sex balanced (half females).
Each sample characteristics value represents:
characteristics: Basename = the usual identifier of the methylation array comprised of the SENTRIX ID (i.e. chip identifier) and position (row and column).
characteristics: Age = Age at the time of sacrifice. 6 months old mice.
characteristics: Sex = F for female mice and M for male mice.
characteristics: Genotype = Huntington disease status genotype status: Q175 is the heterozygous knock-in model of Huntington disease. WT denotes wild type controls.

first: X

middle: W

last: Yang


title: LSD1/KDM1A Maintains Genome-wide Homeostasis of Transcriptional Enhancers [RNA-Seq]

first: Shigeki

last: Iwase

summary: We performed sequencing of Nuclear RNA from Lsd1-WT, Lsd1-GT, KDM5c-WT, and KDM5C-KO mouse embryonic stem cells (mES). We also performed sequencing of Total RNA from Lsd1-WT and Lsd1-GT mES.

overall_design: We performed RNA-Seq in technical duplicates. Nuclei were isolated as described in PMID:21572438 with minor modifications.

first: Saurabh

last: Agarwal


title: Reduced Representation Bisulfite Sequencing from HD knock-in mouse model

summary:
We generated two types of DNA methylation datasets (Reduced Representation Bisulfite Sequencing [RRBS] and custom methylation array) from a heterozygous HD knock-in mouse model. The heterozygous Htt knock-in line expressed one wildtype endogenous Htt allele and a second Htt allele with knock-in of human mHTT exon 1 with either approximately 190 CAG repeats (Q175) or 20 CAG repeats (Q20). For each genotype (Q175 and Q20) we analyzed two brain regions (striatum and cerebellum) from 8 mice each on the RRBS platform (N=32 RRBS samples). Our EWAS of mutant Htt gene status (i.e. Q175 status) across the two brain regions identified two genome-wide significant CpGs in Htt region.
contributor: CHDI foundation

overall_design: Examine DNA methylation differentiation between Htt KI mouse lines Q175 and Q20 mice in cerebellum and striatum brain regions.


title: Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways

status: Public on Jun 04 2020

city: Durham

first: Lihua

last: Ye

state: NC

address: 213 Research Drive, 327 CARL building

department: MGM Department

institute: Duke University

summary: RNA-seq of isolated zebrafish enteroendocrine cells and other intestinal epithelium cells from germ-free (GF) and conventionalized (CV) zebrafish

overall_design: CV and GF TgBAC(cldn15la:EGFP); Tg(neurod1:TagRFP) 8 dpf zebrafish larvae were used for Flow Activated Cell Sorting (FACS) to isolate zebrafish EECs and other IECs. Samples from three independent experimental replicates were performed. 250-580 EECs (n=3 for each CV and GF group) and 100 IECs (n=3 for each CV and GF group) from each experiment were used for library generation and RNA sequencing.

first: Colin

last: Lickwar

first: John

middle: F

last: Rawls

first: Rodger

last: Liddle


title: DNA Methylation Study of Huntington's Disease and Motor Progression in Three Species

sample_organism:
Homo sapiens
Ovis aries
Mus musculus


title: LT-HSC from young (2mo), middle-age (12mo) and old (22mo) mice for RNA-seq

status: Public on Jul 01 2020

first: Jennifer

last: Trowbridge

summary: Long-term hematopoietic stem cells (LT-HSCs) are responsible for lifelong maintenance and regeneration of the blood system. Loss of LT-HSC function is a major contributor to decline in hematopoietic function with aging, leading to increased rate of infection, poor vaccination response, and increased risk of hematologic malignancies. While cellular and molecular hallmarks of LT-HSC aging have been defined1-3, a barrier to achieving the goal of extending healthy hematopoietic function into older age is the lack of understanding of the nature and timing of the initiating events that cause LT-HSC aging. Here we show that hallmarks of LT-HSC aging and decline in hematopoietic function accumulate by middle age in mice, and that the hematopoietic cell-extrinsic bone marrow (BM) microenvironment at middle age is necessary and sufficient to cause LT-HSC aging. Using unbiased transcriptome-based approaches, we identify decreased production of IGF1 by mesenchymal stromal cells (MSC) in the local middle-aged BM microenvironment as a factor causing LT-HSC aging and show that direct stimulation of middle-aged LT-HSCs with IGF1 rescues hallmarks of aging. Together, our study demonstrates that the initiating events causing LT-HSC and hematopoietic aging emerge by middle age and are caused by hematopoietic cell-extrinsic changes in the BM microenvironment. Declining IGF1 in the BM microenvironment at middle age represents a compelling target for intervention using prophylactic therapies to effectively extend healthspan and prevent decline in hematopoietic function during aging.

overall_design: 3 replicates of each condition, LT-HSC from young (2mo), middle-age (12mo) and old (22mo) mice were sorted for RNA-seq

first: Kira

last: Young


title: Expression data of liver with ChREBP gene knockout from mice fed with 60% sucrose diet for 1 week.

status: Public on Jan 24 2020

city: Shanghai

first: Jianhui

last: Shi

state: Shanghai

address: Xiangyin road 800

institute: Navy Medical University

summary:
Carbohydrate response element binding protein (ChREBP) is one of the major transcription factors regulating carbohydrate metabolism and lipogenesis.It expresses highly in several tissues including liver, adipose tissue, small intestine,kidney and muscles. Mice with global knockout of ChREBP exhibit intolerance to carbohydrate including glucose and fructose. However, the exact role of liver ChREBP in high carbohydrate stress is not well defined.
We used microarrays to exame the changes of gene expression pfofile upon high sucrose (50% glucose and 50% fructose) stress when liver ChREBP was deleted.

overall_design: Wild type mice and ChLO mice were houseing under ad lib access to food and water. Livers from 12-week-old mice (n=3 for each group) fed with high sucrose diet  containing 60% sucrose for 1 week were collected for RNA extraction and hybridization on Affymetrix microarrays.