title: The Impact of Zinc on de novo Development of Antibiotic Resistance

status: Public on Jun 13 2023

city: Boston

first: Mark

last: Suprenant

state: MA

address: 44 Cummington Mall

department: BME

institute: Boston University

summary: Antimicrobial resistance (AMR) is a global health crisis that is predicted to worsen. While improper antibiotic usage is an established driver, less is known on the impacts of metal supplements. Here, we probe the impact of zinc (Zn) on AMR.  In conflict settings where diarrhea disease cases are high, Zn, which is associated with weapons of war, is given as a supplement for diarrhea treatment prior to antibiotics such as ciprofloxacin. In this study, we find that E. coli’s exposure order to zinc impacts resistance development, with increasing pre-exposure leading to accelerated ciprofloxacin resistance, while combined exposure of zinc with ciprofloxacin delays ciprofloxacin resistance. We did not find evidence that zinc pre-exposure leads to genetic changes or changes in antibiotic tolerance, though the lag phase and doubling time of E. coli was increased, suggesting gene expression may be changed. While the zinc phenotype was no longer observed if ciprofloxacin exposure did not occur right after zinc pre-exposure, the resulting elevated MIC was more stable. These results are important as they highlight the need to reexamine the clinical role of zinc in treating diarrheal diseases and assess if changes in resistance development observed in vitro are also observed in vivo.

sample_organism: Escherichia coli str. K-12 substr. MG1655

overall_design: To investigate the impact of zinc pre-exposure on resistance development, E.coli cells pre-exposed to zinc and then subinhibitory ciprofloxacin were compared against cells that were not pre-exposed to zinc prior to subinhibitory ciprofloxacin exposure. RNA-seq was then performed on 2 zinc pre-exposed samples and 1 non pre-exposed sample at the end of the pre-exposure time period. This allowed for differential gene expression to be observed between the two conditions.

first: Carly

last: Ching

first: Indorica

last: Sutradhar

first: Neila

last: Gross

first: Jessica

middle: E

last: Anderson

first: Nourhan

last: El Sherif

first: Muhammad

last: Zaman


title: Effects of housing environment, dominance status, and parity on the PBMC transcriptome of sows during gestation and lactation

status: Public on Jun 12 2023

city: Saint-Gilles

first: Mariana

last: Mescouto Lopes

address: 16 Le Clos Domaine de, La Prise

department: UMR Pegase

country: France

institute: INRAe

type: Expression profiling by high throughput sequencing

summary: Blood immune cells transcriptome can be used as a tool to investigate molecular mechanisms or identify biomarkers of several physiological processes. Factors such as reproductive status, age, or physical and mental states resulting from social and non-social environmental aspects can influence the activation and phenotype of immune cells. Here we describe the gene expression levels in peripheral blood mononuclear cells (PBMC) of multiparous sows of various parity ranks housed during gestation in a stable social group either in a conventional environment on a slatted concrete floor (C) or in an enriched environment with deep straw litter and a bigger space allowance (E).

overall_design: Next-generation sequencing was performed in PBMCs of 28 multiparous sows at 98 days of gestation (G98) and 11 days of lactation (L11). The sows were classified according to different parameters,  including the housing environment (C or E), parity rank (high parity sows - HP: 4th gestation or higher and low parity sows - LP: 2nd and 3rd gestation), and dominance status (dominant sows - Dom and subordinate sows - Sub). The experiment was carried out in two replicates (R1 and R2).

first: Caroline

last: Clouard

first: Jennifer

last: Chambeaud

first: Annie

last: Vincent

first: Frederic

last: Hérault

first: Erwan

last: Guichoux

first: Christopher

last: Boury

first: Isabelle

last: Louveau

first: Remi

last: Resmond

first: Hélène

last: Jammes

first: Elodie

last: Merlot


title: Decitabine treatment reveals a functional role of DNA hypomethylation in organising enhancer-promoter interactions [EPIC]

status: Public on Aug 07 2023

city: Adelaide

first: Joanna

last: Achinger-Kawecka

state: SA

address: AHMS Building, North Terrace

country: Australia

institute: South Australian Immunogenomics Cancer Institute

type: Methylation profiling by genome tiling array

summary: DNA methylation is one of the most important epigenetic marks and changes in DNA methylation patterns have been associated with many different types of cancer. Recently, three-dimensional (3D) genome organisation has been demonstrated to play a fundamental role in gene regulation. Determining the interplay between DNA methylation and 3D chromatin structure and function is challenging due to the extreme complexity of epigenetic regulation. To study the impact of DNA methylation on 3D genome organization, we performed a time-course of Decitabine treatment in tamoxifen-resistant MCF7 (TAMR) cells. Decitabine was applied daily for 7 days, followed by “recovery” up to 28 days and DNA methylation (EPIC), gene expression (RNA-seq) and promoter-enhancer interactions (PCHi-C) were assessed on day 7 post-Decitabine- and Vehicle-treatment and day 28 “Recovery” and Vehicle treatment in duplicate. Our data revealed a functional link between DNA hypomethylation at distal enhancer regions, enhancer-promoter interactions, and gene regulation.

overall_design: To understand the role of Decitabine-induced DNA hypomethylation on 3D genome organisation, we used in situ Promoter Capture Hi-C to generate promoter-centric 3D genome maps of TAMR cells treated with Decitabine for 7 days and following 21 days of “recovery”. At the same time, we examined the genome-wide DNA methylation (EPIC Microarrays) and gene expression (RNA-seq) in the same samples.


title: Peripheral human red blood cell development in human immune system (HIS) mouse model with heme oxygenase-1 (HMOX-1) deficiency

status: Public on Aug 03 2023

city: Tarrytown

first: Wei Keat

last: Lim

state: NY

address: 777 Old Saw Mill River Rd

country: USA

institute: Regeneron

summary: A challenge for human immune system (HIS) mouse models has been the lack of  human red blood cells (hRBCs) survival after engraftment of these immune-deficient mice with human CD34+ hematopoietic stem cells (HSCs). Even though human white blood cells can develop in the peripheral blood of these human HSC-engrafted mice, and human erythroid progenitors are found in the murine bone marrow (BM), the hRBCs are quickly phagocytosed by murine macrophages upon egress from the BM. The challenge is further exacerbated by the pathology in BM development that occurs upon complete genetic ablation of murine myeloid cells, rendering such an approach impractical. Heme oxygenase-1 (HMOX-1) deficient mice have reduced macrophages due to toxic build-up of intracellular heme upon engulfment of red blood cells, but do not have an overall loss of myeloid cells. We took advantage of this observation and generated a HMOX-1-/- on a humanized M-CSF/SIRPa/CD47 Rag2-/- IL-2Ryc-/- background. These mice have reduced murine macrophages but comparable level of murine myeloid cells to HMOX-1+/+ control mice in the same background. Injected hRBCs survive longer in HMOX-1-/- mice than in HMOX-1+/+ controls. Since hRBC are present in the peripheral blood of engrafted HMOX-1-/- mice, these mice have the potential to be used for hematological disease modeling, and to test therapeutic treatments for hRBC diseases in vivo.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Spleen and bone marrow will be harvested from 3 different cohorts of engrafted HMOX-1 KO mice (HSC donor-matched; 3 mice per cohort). Single cell suspension will be prepared and mCD45+ cells and hCD45+ cells sorted from each tissue. Samples from each tissue and species will be hashed and used for single cell analysis of leukocyte subsets.

first: Aditi

middle: K

last: Patel

first: Kyle

last: Trageser

first: Hyunjin

last: Kim

first: Wei

first: Christina

last: Adler

first: Stephen

last: Porter

first: Min

last: Ni

first: Yi

last: Wei

first: Mickey

last: Atwal

first: Jun

last: Zhong

first: Lynn

last: Macdonald

first: Andrew

last: Murphy

first: Naxin

last: Tu

first: Davor

last: Frleta


title: Sex-Dependent Transcriptional Changes in response to stress in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

status: Public on Jun 19 2023

city: Fort Lauderdale

first: Lubov

last: Nathanson

state: Florida

address: 3321 College Ave.

department: INIM

institute: Nova Southeastern University

summary: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multi-symptom illness characterized by debilitating fatigue and post-exertional malaise (PEM). Numerous studies have reported sex differences at the epidemiological, cellular, and molecular levels between male and female ME/CFS patients. To gain further insight into these sex-dependent changes, we evaluated differential gene expression by RNA-sequencing in 35 ME/CFS patients (24 female, 11 male) and 34 matched healthy control participants (21 female and 13 male) during and after an exercise challenge intended to provoke PEM. The effects of exertion in the male ME/CFS cohort highlighted pathways related to immune cell signaling (including IL-12) and NK cell cytotoxicity, while female ME/CFS patients did not have significant enough changes in gene expression to meet criteria for our study. Functional analysis during recovery from exercise showed that male ME/CFS patients had distinct changes in regulation of specific cytokine signals (including IL-1β). Female ME/CFS patients had significant alterations in gene networks related to cell stress, response to herpes viruses and NF-kβ signaling. The functional pathways and differentially expressed genes highlighted in this study provide insight into sex-specific predisposition and pathophysiology of ME/CFS.

overall_design: Comparative gene expression analysis of RNA-seq data for female and male ME/CFS patients and matching female and male controls undergoing exercise challenge

first: Jackson

last: Gamer

first: Derek

last: Van Booven

first: Oskar

last: Zarnowski

first: Sebastian

last: Arango

first: Melanie

last: Perez

first: Fanny

last: Collado

first: Nancy

last: Klimas

first: Elisa

last: Oltra


title: Integrative multi-omics analysis uncovers tumor-immune-gut axis influencing immunotherapy outcomes in ovarian cancer

status: Public on May 17 2023

city: BUFFALO

first: Eduardo

last: Cortes

address: ELM AND CARLTON STREETS

department: Biostatistics and Bioinformatics

institute: ROSWELL PARK CANCER INSTITUTE

summary: Recurrent ovarian cancer patients, especially those resistant to platinum, lack effective curative treatments. To address this, we conducted a phase 2 clinical trial (NCT02853318) combining pembrolizumab with bevacizumab, to increase T cell infiltration into the tumor, and oral cyclophosphamide, to reduce the number of regulatory T cells. The trial accrued 40 heavily pretreated recurrent ovarian cancer patients. The primary endpoint, progression free survival, was extended to a median of 10.2 months. The secondary endpoints demonstrated an objective response rate of 47.5%, and disease control in 30% of patients for over a year while maintaining a good quality of life. We performed comprehensive molecular, immune, microbiome, and metabolic profiling on samples of trial patients. Here, we show increased T and B cell clusters and distinct microbial patterns with amino acid and lipid metabolism are linked to exceptional clinical responses. This study suggests the immune milieu and host-microbiome can be leveraged to improve antitumor response in future immunotherapy trials.

overall_design: RNA-seq analysis of tumor samples from R and NR patients

first: Spencer

middle: R

last: Rosario

first: Mark

middle: D

last: Long

first: Shanmuga

last: Chilakapati

first: Sebastiano

last: Battaglia

first: Prashant

last: Singh

first: Jianmin

last: Wang

first: Katy

first: Kristopher

last: Attwood

first: Song

last: Liu

first: Suzanne

last: Hess

first: Robert

last: McGray

first: Kunle

last: Odunsi

first: Brahm

last: Segal

first: Gyorgy

last: Paragh

first: Jennifer

last: Wargo

first: Emese

last: Zsiros


title: Sites of transcription initiation drive mRNA isoform selection [Human_3seq]

status: Public on May 10 2023

city: Freiburg

first: Valérie

last: Hilgers

address: Stübeweg 51

country: Germany

institute: MPI of Immunobiology and Epigenetics

summary: The generation of distinct messenger RNA isoforms through alternative RNA processing influences the expression and function of genes, often in a cell-type specific manner. Here, we assess the regulatory relationships between transcription initiation, alternative splicing,  and 3ʹ end site selection. Applying multiple long-read-sequencing approaches to obtain an assembly accurately representing even the longest transcripts from end to end, we quantify mRNA isoform choice in Drosophila and human tissues, including the transcriptionally complex nervous system. We find that in Drosophila brains as well as in human cerebral organoids, 3ʹ end site choice is globally influenced by the site of transcription initiation. “Dominant promoters”, characterized by specific epigenetic signatures including p300/CBP binding, impose a transcriptional constraint to define splice and polyadenylation variants. In vivo deletion or overexpression of dominant promoters as well as CBP/p300 loss disrupted the 3ʹ end expression landscape. Our study demonstrates the crucial impact of TSS choice on the regulation of transcript diversity and tissue identity.

overall_design: 3'end sequencing of RNA from 60 days-old iPSC-derived cerebral organoids

first: Carlos

last: Alfonso-Gonzalez

first: Ivano

last: Legnini

first: Sarah

last: Holec

first: Laura

last: Arrigoni

first: Hasan

middle: C

last: Ozbulut

first: Fernando

last: Mateos

first: David

last: Koppstein

first: Ulrike

last: Bönisch

first: Agnieszka

last: Rybak-Wolf

first: Nikolaus

last: Rajewsky


title: Development of blood biomarkers that distinguish pancreatic cancer from biliary tract cancer

status: Public on Jun 30 2023

city: Kanagawa

first: Satoko

last: Takizawa

state: Kamakura

country: Japan

institute: Toray Industries, Inc.

summary:
We have developed a method for diagnosing pancreatic cancer and bile duct cancer based on miRNA expression information in the circulating blood.
2565 miRNAs in 426 serum samples were analyzed.

overall_design: The design of this series was constructed in 257 hepatocellular carcinoma (HCC) patients and 41 cholangiocarcinoma carcinoma (ICC) patients and two gall bladder cancer patients.

first: Y

last: Murakami

first: Y-h

last: Taguchi


title: A bile metabolite atlas reveals infection-triggered interorgan mediators of intestinal homeostasis and defense

status: Public on May 02 2023

first: Ting

last: Zhang

address: 181 longwood Ave

institute: BWH

summary: An essential function of the liver is the formation of bile. This aqueous solution is critical for fat absorption and is transported to the duodenum via the common bile duct. Despite extensive studies of bile salts, other components of bile are less well-charted. Here, we characterized the murine bile metabolome and investigated how the microbiota and enteric infection influence bile composition. We discovered that the bile metabolome is not only substantially more complex than appreciated but is dynamic and responsive to the microbiota and enteric infection. Hepatic transcriptomics identified enteric infection-triggered pathways that likely underlie bile remodeling. Enteric infections stimulated elevation of four dicarboxylates in bile that modulated intestinal gut epithelial and microbiota composition, inflammasome activation, and host defense. Our data suggest that enteric infection-associated signals are relayed between the intestine and liver and induce transcriptional programs that shape the bile metabolome, modifying bile’s immunomodulatory and host defense functions.

overall_design: Comparative transcriptome analysis of liver from uninfected, Citrobacter rodentium-infected, and Listeria monocytogenes-infected mice

first: Matthew

last: Waldor


title: Supraphysiological Androgens Promote the Tumor Suppressive Activity of the Androgen Receptor Through cMYC Repression and Recruitment of the DREAM Complex

status: Public on May 26 2023

city: Seattle

first: Brian

last: Hanratty

state: WA

address: 1100 Fairview Avenue

department: Division of Human Biology

institute: Fred Hutchinson Cancer Cancer

type: Genome binding/occupancy profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Evi1 governs Kdm6b-mediated histone demethylation to finely regulate the Laptm4b-driven mTORC pathway in vivo

status: Public on Jun 27 2023

city: Charlottesville

first: Yong

last: Huang

state: VA

address: 1340 Jefferson Park Ave

department: Medicine

institute: University of Viginia


title: Multi-omics of Bohring-Opitz syndrome truncating ASXL1 mutations identify canonical and non-canonical Wnt signaling dysregulation [RNA-seq Fibro]

status: Public on Apr 27 2023

city: Los Angeles

first: Valerie

last: Arboleda

address: 615 Charles E. Young Drive South

institute: UCLA

summary:
We performed gene expression profiling analysis using data obtained from RNA-seq of BOS patient and control individual fibroblast samples to dissect the transcriptomic effects of truncating ASXL1 mutations.
We performed gene expression profiling analysis using data obtained from RNA-seq of BOS patient and control individual fibroblast samples.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Bohring-Opitz syndrome patient blood samples and control blood samples.

first: Isabella

last: Lin

first: Angela

last: Wei


title: Multi-omics of Bohring-Opitz syndrome truncating ASXL1 mutations identify canonical and non-canonical Wnt signaling dysregulation [CUT&RUN Fibro]

summary:
We performed genome-wide analysis of protein-DNA binding using data obtained from CUT&RUN of BOS patient and control individual fibroblast samples to dissect the effects of truncating ASXL1 mutations.
We performed genome-wide analysis of protein-DNA binding using data obtained from CUT&RUN of BOS patient and control individual fibroblast samples.

overall_design: CUT&RUN (Cleavage Under Targets & Release Using Nuclease) for the histone modifications H3K4me3 and H3K27me3 in BOS patient and control fibroblast cells.


title: Multi-omics of Bohring-Opitz syndrome truncating ASXL1 mutations identify canonical and non-canonical Wnt signaling dysregulation [RNA-seq blood]

summary:
We performed gene expression profiling analysis using data obtained from RNA-seq of BOS patient and control individual blood samples to dissect the transcriptomic effects of truncating ASXL1 mutations.
We performed gene expression profiling analysis using data obtained from RNA-seq of BOS patient and control individual blood samples.


title: Zfp36l1 establishes the high affinity CD8 T cell response by directly linking TCR affinity to cytokine sensing

status: Public on Apr 24 2023

city: Cambridge

first: Louise

last: Matheson

address: Babraham Research Campus

department: Laboratory of Lymphocyte Signalling and Development

country: United Kingdom

institute: The Babraham Institute

summary: The T cell effector phase is dominated by few T cells with high affinity TCR for the respective immunodominant antigen. During priming T cells have to process multiple cues in form of antigen, costimulation and cytokines, thus a plethora of T cells with different specificities and affinities has to compete for these cues. IL2 has been suggested to be a pivotal pleiotropic molecule which organizes the quantity, quality and clonal composition of T cells contributing to the effector response. How individual T cells compete for and respond to IL2 and other key cytokines at the molecular level and as a consequence, how this competition shapes population dynamics is still poorly understood.   Here we describe how the RNA binding protein ZFP36L1 acts as a sensor of antigen affinity and establishes dominance of high affinity T cells by promoting the response to IL2.

overall_design: RNA-seq libraries were prepared from OT-I transgenic naïve CD8+ Tcells, following stimulation for 0, 1.5, 3, 6 or 16h, with 2-3 replicates for control and Zfp36/Zfp36l1 double KO mice. 500.000 cells in 0.2ml IMDM+10%FCS, 50uM beta-Me and 40U Penicillin /Streptomycin were stimulated with 0.1nM N4 peptide. Samples with corresponding genotype and replicate number were from the same mouse: except for WT1/WT4, sufficient cells were obtained such that libraries could be generated for all five timepoints from a single mouse.

first: Georg

last: Petkau

middle: S

first: Martin

last: Turner


title: Acute, reversible dietary effect on the transcriptomic profiles of intestinal epithelial cells

status: Public on Apr 12 2023

city: Bronx

first: Wenge

last: Li

address: 1300 Morris Park Avenue

institute: Albert Einstein College of Medicine

summary: Using single cell RNAseq assay, we examine the effect of acute diet-swtiching on the transcriptomic profiles of various intestinal epithelial cells.

overall_design: single cell RNAseq

first: Xusheng

first: Jiahn

last: Choi

first: Leonard

last: Augenlicht


title: Crnic Institute Human Trisome Project - Trisomy 21 Model Atlas: PolyA RNA-seq from C57BL/6 and Dp16 adult mouse lung tissue ± JAK1/2 inhibition with baricitinib

status: Public on Apr 21 2023

city: Aurora

last: Galbraith

state: CO

department: Department of Pharmacology; Linda Crnic Institute for Down Syndrome

summary: Analysis of steady-state mRNA levels in adult mouse lung tissue at 7-11 weeks  from wild-type C57BL/6 and Dp16 mice ± treatment with the JAK1/2 inhibitor baricitinib. This dataset is part of the Human Trisome Project - Trisomy 21 Model Atlas run by the Linda Crnic Institute for Down Syndrome at the University of Colorado Anschutz Medical Campus. http://www.trisome.org/

overall_design: Comparison of wild-type+vehicle (n=2), wild-type+baricitinib (n=2), Dp16+vehicle (n=4), Dp16+baricitinib (n=4).

first: Kelly

last: Sullivan

first: Joaquin

middle: M

last: Espinosa


title: Crnic Institute Human Trisome Project - Trisomy 21 Model Atlas: PolyA RNA-seq from C57BL/6 and Dp16 adult mouse liver tissue ± JAK1/2 inhibition with baricitinib

status: Public on Apr 19 2023

summary: Analysis of steady-state mRNA levels in adult mouse liver tissue at 7-11 weeks  from wild-type C57BL/6 and Dp16 mice ± treatment with the JAK1/2 inhibitor baricitinib. This dataset is part of the Human Trisome Project - Trisomy 21 Model Atlas run by the Linda Crnic Institute for Down Syndrome at the University of Colorado Anschutz Medical Campus. http://www.trisome.org/


title: Dietary induced dedifferentiation of Bmi1 cells and its impact on intestinal mucosal homeostasis

summary: Bmi1tm1(cre/ERT2)Mrc/J (a.k.a. Bmi1creERT2 mice), B6.Cg-Gt(ROSA)26Sortm14(CAT-tdTomato)Hze/J (a.k.a. Rosa26tom mice) were crossed. The mice were fed with New Western diet 1 (NWD1) or Americal Instititue of Nutrition 76A (AIN76A or AIN) diet from weaning for 3 months. Tamoxinfen was injected to induce Bmi1 cell dedifferentiation, featuring the expression of tomato red fluoresence in the Bmi1 locus. Single intestinal epithelial cells were FACS isolated by the Epcam+, CD45- and Tomato (red fluorescence)+, and subject to scRNAseq assay.

overall_design:
Examine roles of dedifferentiation of Bmi1 cell in regeneration of intestinal stem cells and its impact on mucosal homeostasis under normal physiogical condition (fed with various diets).
contributor: Karina


title: Reversible dietary effect on intestinal stem cells

summary: We report the application of bulk RNAseq assay in examining the dietary effect on mouse intestinal stem cell (ISC) subpopulation.  Lgr5EGFPcreERT2 mice were fed with new western diet 1 (NWD1) or the control AIN76A diet for 3 or 12 months, to investigate differential dietary effect. To examine the reversibility of dietary effect, after 3 months of NWD1 feeding, the mice were switched to AIN feeding, and examined at 6 or 12 months old.

overall_design:
Examine differential dietary effect on the transcriptome profile of ISC cells
After weaning, Lgr5EGFPcreERT2 mice were fed with AIN or NWD1 for 3 or 12 months and subjected to RNAseq examination. For Crossover experiments, after 3 months feeding of NWD1, the diet was switched to AIN, and mice were examined in 6 months or 12 months.


title: Supraphysiological Androgens Promote the Tumor Suppressive Activity of the Androgen Receptor Through cMYC Repression and Recruitment of the DREAM Complex [RNA-seq]

first: Ilsa

last: Coleman

address: 1100 Fairview Ave N, E2-112

department: Human Biology

institute: Fred Hutchinson Cancer Center

summary: The androgen receptor (AR) pathway regulates key cell survival programs in prostate epithelium. Targeting the AR has a remarkable therapeutic index and represents a near-universal driver and therapeutic vulnerability in metastatic prostate cancer. Though most approaches directed toward the AR focus on inhibiting AR signaling, laboratory and now clinical data have shown that high dose, supraphysiological androgen treatment (SPA), results in growth repression and improved outcomes in subsets of prostate cancer patients. However, the mechanism(s) contributing to SPA response and resistance remain unclear. To characterize SPA signaling, we integrated metrics of gene expression changes induced by SPA together with cistrome data and protein-interactomes. These analyses determined that the Dimerization partner, RB-like, E2F and Multi-vulval class B (DREAM) complex mediates growth repression and downregulation of E2F targets in response to SPA. Notably, prostate cancers with complete genomic loss of RB1 responded to SPA treat-ment whereas loss of DREAM complex components such as RBL1/2 promoted resistance. Over-expression of MYC resulted in complete resistance to SPA and attenuated the SPA/AR-mediated repression of E2F target genes. These findings support a model of SPA-mediated growth repression that relies on the negative regulation of MYC by AR leading to repression of E2F1 signaling via the DREAM-SIN3A-HDAC complex. As RB1 and DREAM complex stabil-ity are regulated by MYC, a key determinant of tumor sensitivity to SPA, treatment may hinge on effectively repressing MYC activity. The integrity of MYC signaling and DREAM complex assembly may consequently serve as determinants of SPA responses and as pathways mediating SPA resistance.

overall_design: RNA sequencing of human prostate tumor cell lines using Illumina TruSeq Stranded mRNA Library prep and sequenced on Illumina HiSeq 2500 and NovaSeq 6000.

first: Michael

last: Nyquist

first: Jared

last: Lucas

first: Hannah

last: Meade

first: Dapei

first: Elahe

middle: A

last: Mostaghel

first: Stephen

last: Plymate

first: Eva

last: Corey

last: Haffner

first: Peter

last: Nelson


title: Functional unloading leads to metabolic and functional disorders in FAPs in vitro

status: Public on Apr 10 2023

city: Saint-Petersburg

first: Margarita

last: Sorokina

address: Akkuratova 2

country: Russia

institute: Almazov National Medical Research Centre

summary: In our study, we used hindlimb unloading rat model to study fibro-adipogenic progenitor cells (FAPs) condition in muscle atrophy.  We have purified FAPs from m. soleus from control rats and after 7 and 14 days of immobilization (HS7, HS14). Also, we performed adipogenic differentiation of FAPS in vitro during 3 days.

overall_design: Libraries were prepared with TruSeq Stranded mRNA kit, samples were RNA-sequenced on Illumina NextSeq 2000, read length 51 bp.

middle: Y

first: Oksana

last: Ivanova

first: Renata

middle: I

last: Dmitrieva

first: Natalia

last: Vilchinskaya

first: Boris

last: Shenkman


title: Transcriptional characterization of  ABCC1 and ABCB1 KO and MZ1 treated WT HAP1 cell lines.

status: Public on Jun 07 2023

city: Vienna

first: Giulio

last: Superti-Furga

address: Lazarettgasse 14

country: Austria

institute: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences

summary: We used CRISPR/Cas9 to intoroduce frame-shifting mutations into the ABCC1 and ABCB1 genes and treated HAP1 WT cells with varying concentrations of the MZ1 PROTAC. To measure the transcriptional response to both genetic and chemical perturbances, we performed RNA-seq and quantified gene expression levels.

overall_design: 6 cell lines, untreated or MZ1 treated in 1-3 technical replicates

first: Gernot

last: Wolf

first: Svenja

last: Onstein

first: Eirini

last: Christodoulaki


title: Molecular insights into the lipid-carbohydrates metabolism switch under the endurance effort in Arabian horses

status: Public on Apr 04 2023

city: Krakow

first: Tomasz

last: Szmatoła

state: Małopolskie

address: Mickiewicza 21

department: OMEI

country: Poland

institute: University of Agriculture in Krakow

summary: Purpose: RNA-sequencing (RNA-seq) was used to identify the changes in gene expression profile to describe the metabolism adaptation at the whole transcriptome of blood  to endurance effort. Samples from ten Arabian horses were taken before and after a 120km long endurance ride.

overall_design:
Methods: The blood samples from each horse were taken twice – before and after the run,  by jugular venipuncture into Tempus™ Blood RNA Tube (Applied Biosystems, Thermo Fisher Scientific, Waltham, MA, USA) and stored at -20°C (n=20) until analysis. RNA was isolated with PureLink™ RNA mini kit. The quality and quantity of obtained libraries (the TruSeq RNA Kit v2 kit (Illumina, San Diego, CA, USA) ) were assessed using Qubit 2.0 (Qubit™ dsDNA BR AssayKit, Invitrogen, Waltham, MA, USA ) and TapeStation 2200 (D100 screencaps, Agilent). Next, the cDNA libraries were sequenced on NextSeq 500 Illumina platform (Illumina, San Diego, CA, USA) and NextSeq 500/550 High Output KIT v 2.5 (75 cycles) according to protocol. The qPCR validation was used to confirm RNA-seq data.
Results: The results, including KEGG (Kyoto Encyclopaedia of Genes and Genomes) and GO (Gene Ontology) analyses allowed us to describe the most significantly up-regulated – ARV1, DGAT2, LIPE, APOA2, MOGAT1, MOGAT2, GYS1, GYS2 and down-regulated - ACACA, ACACB, FADS1, FADS2 genes involved in carbohydrate and lipid metabolism. Also, the increased expression of RAF1, KRAS and NRAS genes involved in the Insulin pathway and PI3K-Akt was shown. The general insight into processes described  in the present study may confirm the thesis of the lipid-carbohydrates metabolism switch and provide the basis for further research.
Conclusions: In our research, we aimed to unravel the complexity of metabolic changes at the molecular level in Arabian horses after exposure to heavy endurance physical effort. The presented results have shown significant changes in carbohydrate and fat metabolism reflected a modification of several pathways critical for the maintenance of homeostasis as well as energy use and production. The general insight into the processes described in the present study seems to confirm the thesis of the lipid-carbohydrates metabolism switch under the endurance effort and allow us to propose the panel of marker genes critical for endurance predisposition.
The whole transcriptome sequencing of equine blood was performed for 10 samples using NextSeq 550High Output KIT v2.5 (Illumina) into 75 single-end cycles.

first: Grzegorz

last: Myćka

first: Katarzyna

last: Ropka-Molik

first: Anna

last: Cywińska

first: Monika

last: Stefaniuk-Szmukier


title: The MMP-2 histone H3 N-terminal tail protease is selectively targeted to the transcription start sites of active genes [RNA-seq]

status: Public on May 05 2023

city: New York

first: Benjamin

middle: H

last: Weekley

address: 1470 Madison Ave

department: Neuroscience

institute: Icahn School of Medicine at Mount Sinai

summary: Our study examines the role of MMP-2 mediated Histone H3NT proteolysis in U2OS cells. We find binding of MMP-2 at all active protein coding transcription start sites, and examine the role it plays in local chromatin regulation and changes in gene expression.

overall_design: RNA-seq of U2OS WT cells and MMP-2 KD cells (2 different shRNAs, 23 and 26) at three different stages of confluency

first: Judd

last: Rice


title: Loratadine's antibiotic adjuvant effects in MRSA 43300

status: Public on Mar 23 2023

city: High Point

first: Heather

middle: Bennett

last: Miller

state: NC

address: One University Parkway

department: Chemistry

institute: High Point University

summary: Methicillin-resistant Staphylococcus aureus (MRSA) is a major threat to human health. Rather than depend on creating new antibiotics (to which bacteria will eventually become resistant), we are employing antibiotic adjuvants that potentiate existing antibiotics. Based on our previous work, loratadine, the FDA-approvide antihistamine, effectively potentiates cell-wall active antibiotics in multiple strains of MRSA. Furthermore, loratadine and oxacillin helped disrupt preformed biofilms and stop them from initially forming in vitro. To gain biological insight into how this potentiation and biofilm inhibition occurs, we used RNA-seq on treated MRSA 43300 cultures to examine antibiotic adjuvant affects transcritome-wide.

overall_design: Differential gene expression was examined between MRSA cultures either untreated, treated with oxacillin only, treated with an antibiotic adjuvant (loratadine), or cotreated with oxacillin and loratadine. Each of the four treatments was performed with biological triplicates.

middle: B


title: m6A RNA methylation orchestrates transcriptional dormancy during paused pluripotency

city: Toronto

first: Evelyne

middle: Anne

last: Collignon

state: ON

address: 60 Murray Street, Box42,

country: Canada

institute: Lunenfeld-Tanenbaum Research Institute


title: Chromatin profiling of GM12878 cells with and without a predicted enhancer element

status: Public on Mar 07 2023

city: Boulder

first: Edward

last: Chuong

state: Colorado

address: 3415 Colorado Ave, JSCBB E251

institute: University of Colorado Boulder

summary: We test the predicted interferon-inducible enhancer activity of a LINE within the first intron of the IFNAR1 gene (IFNAR1.L1M2a) by knocking out the predicted enhancer using CRISPR, and assessing chromatin and polymerase II occupancy in untreated and interferon beta-treated conditions compared to wildtype cells

overall_design: Profiling of histone marks H3K27ac, H3K9me3, as well as PolII were conducted by CUT&Tag in human lymphoblastoid cell line GM12878. Cells were either wildtype, clonal wildtype lines, or CRISPR knockout clonal lines lacking a LINE-derived predicted enhancer within the first intron of the IFNAR1 gene. Cells were either untreated, or treated for 4 hours with 10 units per mL of human interferon beta

first: Carmen

last: Buttler


title: Crnic Institute Human Trisome Project: PolyA RNA-seq from whole blood

status: Public on Mar 20 2023

first: Matthew

last: Galbraith

summary: Analysis of steady-state mRNA levels in whole blood of euploid controls and subjects with trisomy 21. This dataset is part of the Human Trisome Project run by the Linda Crnic Institute for Down Syndrome at the University of Colorado Anschutz Medical Campus. http://www.trisome.org/

overall_design: Comparison of trisomy 21 (T21) subjects (n=304) to euploid controls (n=96)

first: Angela

middle: L

last: Rachubinski

first: Keith

middle: P

last: Smith

first: Kelly

last: Sullivan

first: Joaquin

last: Espinosa


title: Interferon beta response in LCLs with and without a predicted enhancer

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


title: Transcriptional response to interferon beta and effects of deletion of a predicted enhancer

summary: We test the effect of CRISPR knockout of a predicted interferon inducible enhancer within the first intron of the IFNAR1 gene (IFNAR1.L1M2a) on the transcriptional response of GM12878 cells to treatment with interferon beta

overall_design: Clonal wildtype GM12878 lines and clonal CRISPR knockout lines lacking a predicted enhancer within the first intron of the the IFNAR1 gene were either untreated or treated with 10 units per ml of human interferon beta over a time course of 4, 12, and 24 hours, and then profiled by RNA-seq


title: Sites of transcription initiation drive mRNA isoform selection [RNAseq2]

status: Public on May 10 2023

first: Valérie

last: Hilgers

summary: The generation of distinct messenger RNA isoforms through alternative RNA processing influences the expression and function of genes, often in a cell-type specific manner. Here, we assess the regulatory relationships between transcription initiation, alternative splicing,  and 3ʹ end site selection. Applying multiple long-read-sequencing approaches to obtain an assembly accurately representing even the longest transcripts from end to end, we quantify mRNA isoform choice in Drosophila and human tissues, including the transcriptionally complex nervous system. We find that in Drosophila brains as well as in human cerebral organoids, 3ʹ end site choice is globally influenced by the site of transcription initiation. “Dominant promoters”, characterized by specific epigenetic signatures including p300/CBP binding, impose a transcriptional constraint to define splice and polyadenylation variants. In vivo deletion or overexpression of dominant promoters as well as CBP/p300 loss disrupted the 3ʹ end expression landscape. Our study demonstrates the crucial impact of TSS choice on the regulation of transcript diversity and tissue identity.

overall_design: Short-read sequencing of Drosophila melanogster embryos 14-16hours old (Neijre mutants and w1118 control) or 16-18hours old (others chromatin modifier mutants and w1118 control)

first: Carlos

last: Alfonso-Gonzalez

first: Ivano

last: Legnini

first: Sarah

last: Holec

first: Laura

last: Arrigoni

first: Hasan

last: Ozbulut

first: Fernando

last: Mateos

first: David

last: Koppstein

first: Ulrike

last: Bönisch

first: Agnieszka

last: Rybak-Wolf

first: Nikolaus

last: Rajewsky


title: Multi-omics of Bohring-Opitz syndrome truncating ASXL1 mutations identify canonical and non-canonical Wnt signaling dysregulation

first: Valerie

last: Arboleda

overall_design: Refer to individual Series


title: A nucleosome switch primes Hepatitis B Virus infection

status: Public on Mar 03 2023

first: Andres

last: Mansisidor

address: 1230 York Ave Box 176

department: Laboratory of Genome Architecture and Dynamics

institute: Rockefeller University

sample_organism:
Homo sapiens
Hepatitis B virus

platform_organism:
Homo sapiens
Hepatitis B virus


title: Multi-omics of Bohring-Opitz syndrome truncating ASXL1 mutations identify canonical and non-canonical Wnt signaling dysregulation [ATAC-seq Fibro]

summary:
We performed genome-wide chromatin accessibility analysis using data obtained from ATAC-seq of BOS patient and control individual fibroblast samples to dissect the chromatin regulating effects of truncating ASXL1 mutations.
We performed genome-wide chromatin accessibility analysis using data obtained from ATAC-seq of BOS patient and control individual fibroblast samples.

overall_design: Comparative genome-wide chromatin accessibility analysis of ATAC-seq data for Bohring-Opitz syndrome patient fibroblast samples and control fibroblast samples.

first: Isabella

last: Lin

first: Angela

last: Wei


title: A nucleosome switch primes Hepatitis B Virus infection [Mnase-Seq, ChIP-Seq]

summary: Chronic hepatitis B virus (HBV) infection is an incurable global health threat responsible for causing liver disease and hepatocellular carcinoma. During the genesis of infection, HBV establishes an independent minichromosome consisting of the viral covalently closed circular DNA (cccDNA) genome and host histones. The viral X gene must be expressed immediately upon infection to induce degradation of the host silencing factor, Smc5/6. However, the relationship between cccDNA chromatinization and X gene transcription remains poorly understood. Establishing a reconstituted viral minichromosome platform, we found that nucleosome occupancy in cccDNA drives X transcription. We corroborated these findings in cells and further showed that the chromatin destabilizing molecule CBL137 inhibits X transcription and HBV infection in hepatocytes. Our results shed light on a long-standing paradox and represent a potential new therapeutic avenue for the treatment of chronic HBV infection.

overall_design: We performed RNA-seq and MNase-seq on HEK293T cells that were transfected with hepatitis B virus (HBV) cccDNA over different timepoitns post transfection. We also performed MNase-seq on HBV cccDNA that was reconstituted with nucleosomes at different levels of saturation. Finally, we performed ChIP-seq on cells either constitutively modeling HBV infection (HepAD38) or that were transfected with HBV cccDNA (HepG2).

first: Nicholas A

last: Prescott

first: Andrés

first: Yaron

last: Bram

first: Tracy

last: Biaco

first: Justin

last: Rendleman

last: Faulkner

first: Abigail

last: Lemmon

first: Christine

last: Lim

first: Pierre-Jacques

last: Hamard

first: Richard

last: Koche

first: Viviana

last: Risca

first: Robert

last: Schwartz

first: Yael

last: David


title: A rapid microglial metabolic response controls metabolism and improves memory

status: Public on Feb 21 2023

city: Grand Rapids

first: Luca

last: Fagnocchi

state: MI

address: 333 Bostwick AVE NE

institute: VAI

summary: Chronic high-fat feeding triggers widespread metabolic dysfunction including obesity, insulin resistance, and diabetes. While these ultimate pathological states are relatively well understood, we have a limited understanding of how high-fat intake first triggers physiological changes. Here, we identify an acute microglial metabolic response that rapidly translates intake of high-fat diet (HFD) to a surprisingly beneficial effect on spatial and learning memory. Acute high-fat intake increases palmitate levels in cerebrospinal fluid and triggers a wave of microglial metabolic activation characterized by mitochondrial membrane activation, fission and metabolic skewing towards aerobic glycolysis. These effects are generalized, detectable in the hypothalamus, hippocampus, and cortex all within 1-3 days of HFD exposure. In vivo microglial ablation and conditional DRP1 deletion experiments show that the microglial metabolic response is necessary for the acute effects of HFD. 13C-tracing experiments reveal that in addition to processing via β-oxidation, microglia shunt a substantial fraction of palmitate towards anaplerosis and re-release of bioenergetic carbons into the extracellular milieu in the form of lactate, glutamate, succinate, and intriguingly, the neuro-protective metabolite itaconate. Together, these data identify microglial cells as a critical nutrient regulatory node in the brain, metabolizing away harmful fatty acids and liberating the same carbons instead as alternate bioenergetic and protective substrates. The data identify a surprisingly beneficial effect of short-term HFD on learning and memory.

overall_design: Expression profile of single microglial cells, isolated from brain of wild type mice, either under normal chow (NC) or 3 days of high fat diet (HFD) treatment.

first: Anne

last: Drougard

first: J

last: Pospisilik


title: Impact of knocking out Ppargc1a in intestinal stem cells on mucosal homeostasis

first: Wenge

last: Li

summary: We report the application of single cell RNAseq assay in examining the effect of Ppargc1a gene expression in intestinal stem cells on mucosal homeostasis.  Lgr5EGFPcreERT2 mice were crossed with Ppargc1a F/+ or F/F to selectively target gene expression in Lgr5 expressing intestinal stem cells. Mice were fed with control diet AIN76A from weaning for 3 months, and deletion of Ppargc1a gene was conducted via Tamoxifen injection. Mice were sacrificed 3 days post tamoxifen injection.

overall_design: Examine roles of Ppargc1a gene in intestinal stem cells and its impact on mucosal homeostasis.

first: Jiahn

last: Choi

first: Xusheng

last: Zhang

first: Leonard

last: Augenlicht


title: A Comparative Transcriptomics Analysis Reveals Ethylene Glycol Derivatives of Squalene Ameliorate Excessive Lipogenesis and Inflammatory Response in 3T3-L1 preadipocytes cells

status: Public on Feb 18 2023

city: Tsukuba

first: Farhana

last: Ferdousi

state: Ibaraki

address: Tennodai 1-1-1

institute: University of Tsukuba

summary:
[Note: For black soybean's neuroinflammation study, please refer to accession number: GSE270419]

Transcriptomic analysis reveals the anti-excessive lipogenesis and anti-inflammatory effects of SQ and its derivatives on preadipocyte differentiation
We horizontally compared the effects of SQ and its four derivatives on preadipocyte differentiation and anti-inflammation. Di- and tetra-SQ can significantly improve the lipid metabolism function and anti-inflammatory effect of adipocytes, and ameliorate excessive production.

overall_design: RNA was extracted using Isogen (Nippon Gene Co. Ltd., Toyama, Japan). The integrity of RNA was quantified using NanoDrop 2000 spectrophotometer (Thermo Scientific, Wilmington, DE, USA). Clariom S assay system (Thermo Fisher, Japan) was used on duplicate RNA samples of each group. In accordance with the user manual, complementary DNA (cDNA) for microarray was generated using the GeneChip WT Plus Reagent kit (Thermo Fisher Science, Japan). Samples were hybridized using Clariom S GeneChip microarray kit (Thermo Fisher Science, Japan). After washing and staining, images were captured, and then CEL data were generated using the GeneChip Scanner 3000 (Thermo Fisher Science, Japan). The raw CEL data were normalized using the transcriptome analysis console (TAC) software ver.4.0.1 following the SST-robust multichip average (SST-RMA) algorithm (Thermo Fisher Scientific, Japan).

first: Yu

last: Cheng


title: MYT1L is required for suppressing earlier neuronal development programs in the adult mouse brain

status: Public on Mar 02 2023

city: St. Louis

first: Joseph

last: Dougherty

state: MO

address: Couch Biomedical Research Bldg 06316

department: Genetics

institute: Washington University of St. Louis

summary: In vitro studies indicate the neurodevelopmental disorder gene Myelin Transcription Factor 1 Like (MYT1L) suppresses non-neuronal lineage genes during fibroblast-to-neuron direct differentiation. However, MYT1L’s molecular and cellular functions during differentiation in the mammalian brain have not been fully characterized. Here, we found that MYT1L loss leads to up-regulated deep layer (DL) but down-regulated upper layer (UL) neuron gene expression, corresponding to an increased ratio of DL/UL neurons in mouse cortex. To define potential mechanisms, we conducted Cleavage Under Targets & Release Using Nuclease (CUT&RUN) to map MYT1L binding targets in mouse developing cortex and adult prefrontal cortex (PFC), and to map epigenetic changes due to MYT1L mutation. We found MYT1L mainly binds to open chromatin, but with different transcription factor co-occupancies between promoters and enhancers. Likewise, multi-omic dataset integration revealed that, at promoters, MYT1L loss does not change chromatin accessibility but does increase H3K4me3 and H3K27ac, activating both a subset of earlier neuronal development genes as well as BCL11B, a key regulator for DL neuron development. Meanwhile, we discovered that MYT1L normally represses the activity of neurogenic enhancers associated with neuronal migration and neuronal projection development by closing chromatin structures and promoting removal of active histone marks. Further, we show MYT1L interacts with SIN3B and HDAC2 in vivo, providing potential mechanisms underlying any repressive effects on histone acetylation and gene expression. Overall, our findings provide a comprehensive map of MYT1L binding in vivo and mechanistic insights to how MYT1L facilitates neuronal maturation.

overall_design: CUT&RUN was performed using MYT1L, histones, and IgG antibodies on mouse embryonic day 14 (E14) cortex and adult prefrontal cortex (PFC). For E14 cortex, 3 biological replicates (both wild-type and homozygous knockout) were used for MYT1L and IgG, and 2 biological replicates (both wild-type and homozygous knockout) were used for histone CUT&RUN. For PFC, 3 biological replicates  (both wild-type and heterozygous knockout) were used for MYT1L, IgG, and histone CUT&RUN.

first: Jiayang

last: Chen


title: Single-cell immune landscape of human atherosclerotic plaques

status: Public on Feb 01 2023

first: Dr. Chiara

last: Giannarelli

address: 435 E 30th St

department: Cardiology

institute: NYU Langone Health

summary: Using single-cell proteomic and transcriptomic analyses, we uncovered distinct features of both T cells and macrophages in carotid artery plaques of patients with clinically symptomatic disease (recent stroke or transient ischemic attack) compared to asymptomatic disease (no recent stroke). Additionally, macrophages from these plaques contained alternatively activated phenotypes, including subsets associated with plaque vulnerability. In plaques from asymptomatic patients, T cells and macrophages were activated and displayed evidence of interleukin-1β signaling. The identification of specific features of innate and adaptive immune cells in plaques that are associated with cerebrovascular events may enable the design of more precisely tailored cardiovascular immunotherapies.

overall_design: Carotid artery from atherosclerotic human samples, used scRNAseq to under the underlying immune molecular mechanism

first: Chiara


title: COVID-19 drives a distinct plasma proteome in pregnant and non-pregnant individuals

city: Detroit

first: Adi

last: Tarca

address: 3990 John R. St, 4 Brush South

institute: Wayne State University

summary: This study used SomaScan v 4.1 to profile>7000 proteins in human plasma and assess changes with Sars-Cov-2 infection and with Covid-19 disease severity in pregnant and non-pregnant individuals.

overall_design: This is a cross-sectional study that included non infected controls and Sars-Cov-2 infected patients with various degrees of disease serverity.

first: Bogdan

last: Done

first: Nardhy

last: Gomez-Lopez

first: Dahiana

last: Gallo

first: Roberto

last: Romero


title: ZNF827-dependent splicing dynamics are critical for EMT during development and disease

status: Public on Feb 14 2023

city: Stockholm

first: Eneritz

last: Agirre

address: Solnavägen 9

department: MBB

country: Sweden

institute: Karolinska Institutet


title: Molecular Signatures and Functional Analysis of Secondary Hair Follicles in Cashmere Goat During Annual Cashmere Growth

status: Public on Jan 31 2023

city: Shenyang

first: Huiling

last: Xue

address: 120 Dongling Road,110866 Shenyang,China

country: China

institute: Shenyang Agricultural University

summary:
Secondary hair follicles (SHFs) produce the cashmere of goats. In the present study, SHF clusters were isolated under the microscope by cutting out the epidermis and removing the connective tissues. RNA sequencing was performed on the collected SHFs.
Through genome-wide transcriptomic analysis, we discovered and characterized differentially expressed molecular signatures across the annual growth cycle of cashmere and demonstrated their differential expression features and importance in cashmere growth.

overall_design: Gene expression profiling analysis of RNA-seq data for cashmere follicles during annual cashmere growth. RNA sequencing was performed using Illumina HiSeq 4000 platform across six time points, each with two biological replicates (male and female), representing phases of anagen (May and September), catagen (November and December) and telogen (February and March).

first: Minglin

last: Wang

first: Zehao

last: Liu

first: Yanlei

first: Shengda

last: Sheng


title: Transcriptome of amniotic fluid neutrophils and monocytes/macrophages

status: Public on Jan 05 2023

summary: Intra-amniotic infection, the invasion of microbes into the amniotic cavity resulting in an inflammatory process, is a clinical condition that can lead to adverse pregnancy outcomes for the mother and fetus as well as severe long-term neonatal morbidities. Despite much research focused on the consequences of intra-amniotic infection, there is still little knowledge about the functional roles of innate immune cells that respond to invading microbes. In the current study, we performed RNA sequencing of sorted neutrophils and monocytes/macrophages from amniotic fluid from women with intra-amniotic infection to determine the transcriptomic differences between these innate immune cells. Further, we sought to identify specific transcriptomic pathways that were significantly altered by the maternal or fetal origin of amniotic fluid neutrophils and monocytes, the presence of a severe fetal inflammatory response, and pregnancy outcome (i.e. preterm or term delivery). We showed that significant transcriptomic differences exist between amniotic fluid neutrophils and monocytes/macrophages from women with intra-amniotic infection that are indicative of the distinct roles these cells play. We also found that amniotic fluid monocytes/macrophages of fetal origin display impaired ability to clear out microbes invading the amniotic cavity compared to those of maternal origin. Notably, we demonstrate that the transcriptomic changes in amniotic fluid monocytes/macrophages are heavily associated with the severity of the fetal inflammatory response, suggesting that the trafficking of fetal neutrophils throughout the umbilical cord is partially modulated by monocytes/macrophages in the amniotic cavity. Finally, we show that amniotic fluid neutrophils and monocytes/macrophages from preterm deliveries display enhanced transcriptomic activity compared to those from term deliveries, highlighting the protective role of these innate immune cells in this vulnerable period. Collectively, these findings demonstrate the underlying complexity of local innate immune responses in women with intra-amniotic infection, and provide new insights into the functions of amniotic fluid neutrophils and monocytes in the amniotic cavity.

overall_design: A total of 12 samples were included, 6 samples of monocytes/macrophages and 6 samples of neutrophils isolated from the amniotic fluid of 6 unique patients.

first: Aneesha

last: Varrey

first: Yaozhu

last: Leng

first: Derek

last: Miller

first: Yi

last: Xu

first: Gaurav

last: Bhatti

first: Kenichiro

last: Motomura

first: Meyer

last: Gershater

first: Roger

last: Pique-Regi


title: Multiomics Point of Departure (moPOD) Modeling Supports an Adverse Outcome Pathway Network for Ionizing Radiation

status: Public on Jan 01 2023

city: Oslo

first: You

last: Song

address: Økernveien 94

department: Ecotoxicology and Risk Assessment

country: Norway

institute: Norwegian Institute for Water Research (NIVA)

summary: This study aims to investigate dose-dependent transcriptomic responses of Daphnia magna after chronic exposure to gamma radiation. RNA sequecing was performed after 4 days and 8 days exposure. Differentially expressed genes and major pathways enriched were characerized to provide insights into the chronic effects of gamma radiation.

overall_design: Neonatal Daphnia magna were exposed to 0.4-100 mGy/h gamma radiation for

first: Keke

last: Zheng

first: Dag

last: Brede

first: Tânia

last: Gomes

first: Li

last: Xie

first: Yetneberk

last: Kassaye

first: Brit

last: Salbu

first: Knut

last: Tollefsen


title: Transcriptomic study identifies quercetin and rutin as repurposed drugs for Parkinson’s Disease in in vitro 6-OHDA model

city: Gebze

first: Tunahan

last: Cakir

state: Kocaeli

address: Gebze, Kocaeli, Turkey

department: Department of Bioengineering

country: Turkey

institute: Gebze Technical University

summary: SH-SY5Y cells were treated with 6-hydroxydopamine (6-OHDA) to obtain an in vitro PD model. Transcriptome data were collected from both treated and untreated cells.We mapped significantly upregulated genes on a protein-protein interaction network to identify potential drug targets. Drugs targeting the selected drug targets were applied to 6-OHDA treated SH-SY5Y cells.  Among the candidate drugs, quercetin and rutin were shown to be neuroprotective by effectively decreasing cell death.

overall_design: In total, 16 independent experiments were performed to obtain 8 untreated samples and 8 6-OHDA treated samples. Samples were collected at 12th and 18th hours from both treated and control experiments. Each group was run in four replicates.

first: Esra

middle: N

last: Yigit

first: Ekin

last: Sonmez

first: Isa

last: Yuksel

first: Isil

last: Aksan Kurnaz


title: Epigenetic modules governing skin epidermal homeostasis [III]

status: Public on Jan 12 2023

city: Bethesda

first: Stephen

last: Brooks

state: MD

address: 50 SOUTH DR, RM 1140

department: Biodata Mining and Discovery Section

institute: NIAMS/NIH

summary: Skin homeostasis is guided by spatiotemporal regulation of gene expression, establishing each stage of keratinocyte differentiation. The current study presents transcriptomic and chromatin profiling for the proliferating (basal) and differentiated (suprabasal) cell populations derived from neonate mice (p0-p2) skin epidermis. This multi-omic approach will enable idenitification of cell specific epidermal cross-talk central to the equlibirum.

overall_design: Chromatin profiling: Chromatin accessiility and chromosome conformation profiling in basal and suprabasal fractions of skin epidermis; Histone and transcription factor occupancy profiling for suprabasal cells in mouse neonate skin epidermis

first: Subhashree

last: Nayak

first: Kan

last: Jiang

first: Stefania

last: Dell O'rso

first: Maria

last: Morasso


title: Dynamic DNA methylation turnover at the exit of pluripotency epigenetically primes gene regulatory elements for hematopoietic lineage specification

status: Public on Jan 24 2023

city: Cambridge

first: Simon

middle: Richard

last: Andrews

state: Cambs

address: Babraham Research Campus

department: Science Services

institute: The Babraham Institute

type: Methylation profiling by high throughput sequencing

overall_design:
Refer to individual Series

UPDATE: [Jan-16-2025] The GSE223578_interaction_pair_marks.txt.gz file was updated.


title: Characterization of dynamic p300 enhancers in murine cardiomyocyte development

status: Public on Jan 19 2023

city: Boston

first: Pingzhu

last: Zhou

state: MA

address: 320 Longwood Ave

institute: Boston Children's Hospital


title: Losartan controls immune checkpoint blocker-induced edema and improves survival in glioblastoma

first: Elizabeth

last: Perez

address: 30 Fruit Street

institute: MGH

summary: Immune checkpoint blockers (ICBs) have failed in all Phase III glioblastoma trials. Here, we found that ICBs induce cerebral edema in some patients and mice with glioblastoma. Through single-cell RNA sequencing, intravital imaging, and T cell blocking studies in mice, we demonstrated that this edema results from an inflammatory response following anti-PD1 antibody treatment that disrupts the blood-tumor-barrier. Used in lieu of immunosuppressive corticosteroids, the angiotensin receptor blocker losartan prevented this ICB-induced edema and reprogrammed the tumor microenvironment, curing 20% of mice which increased to 40% in combination with standard of care treatment. Using a bihemispheric tumor model, we identified a “hot” tumor immune signature prior to losartan+anti-PD1 therapy that predicted long-term survival. Our findings provide the rationale and associated biomarkers to test losartan with ICBs in glioblastoma patients.

overall_design: single-cell RNA-seq

first: Meenal

last: Datta

first: Sampurna

last: Chatterjee

last: Gritsch

first: Sylvie

last: Roberge

first: Mark

last: Duquette

first: Ivy

middle: X

last: Chen

first: Kamila

last: Naxerova

first: Ashwin

last: Kumar

first: Mitrajit

last: Ghosh

first: Kyrre

middle: E

last: Emblem

first: Mei

last: Ng

first: William

middle: W

last: Ho

first: Pragya

first: Shanmugarajan

last: Krishnan

first: Xinyue

last: Dong

last: Speranza

first: Martha

last: Neagu

first: David

last: Reardon

first: Arlene

last: Sharpe

first: Gordon

middle: J

last: Freeman

first: Mario

last: Suvà

first: Lei

last: Xu

first: Rakesh

middle: K

last: Jain


title: Enhancing wound inducible adaptive fibroblast reprogramming overcomes diabetic healing impairment

status: Public on Dec 27 2022

city: Pittsburgh

first: Chandan

last: Sen

state: Pennsylvania

address: 450 Technology Drive

department: Surgery

institute: University of Pittsburgh

summary: Adaptive cellular reprogramming is an emerging field to study promotion of a host’s intrinsic healing strategies through changing one somatic cell type into another state or fate; tissue injury is known to enhance such cell conversions. Here we identify a molecular pathway in injured skin, whereby a subset of dermal fibroblasts displays a novel vasculogenic state change with gain in vasculogenic transcripts and endothelial cell-like functions without losing core fibroblast lineage fate phenotypic, functional, and transcriptional characteristics. Removal of microRNA suppression of FLI1 transcription in fibroblasts results in upregulation of a cascade of vasculogenic molecules that heralds the vasculogenic state change in some fibroblasts. FLI1 dependent vasculogenic fibroblast subset emergence in injured skin is blunted in poorly healing skin wounds of diabetic animals but can be restored through topical tissue nanotransfection of a single anti-microRNA oligonucleotide, to rescue tissue perfusion and wound healing. Augmenting a physiologic tissue injury adaptive response mechanism that produces vasculogenic fibroblasts opens new avenues for therapeutic tissue vascularization of ischemic conditions.

overall_design: To define the transcriptional changes during HADF reprogramming, single cell RNA sequencing (scRNA-seq) was performed at days 1, 3, 5 and 7 following miRIDIAN microRNA hsa-miR-200b-3p hairpin inhibitor (MI) transfection. To account for the effect of transfection, additional samples were analyzed using control transfection (miRIDIAN microRNA hairpin inhibitor negative control; control inhibitor, CI) at two different time points (d1 and d7 post-transfection).

first: Kanhaiya

last: Singh

first: Ahmed

middle: S

last: Abouhashem

first: Mervin

middle: C

last: Yoder

first: Sashwati

last: Roy

first: Sujit

last: Mohanty

first: Rajneesh

last: Srivastava


title: Transcriptomic profiling of the adult reptilian dentition sheds light on the genes regulating indefinite tooth replacement [scRNA-seq]

status: Public on Dec 24 2022

city: Vancouver

first: Stephane

last: Flibotte

state: BC

address: 2370-6270 University Blvd.

department: Faculty of Science

institute: University of British Columbia

summary: The aim of this study is to discover new genes and cells involved in life-long tooth replacement. Here we study the adult dentition of the leopard gecko (Eublepharis macularius). Bulk RNAseq was used to compare teeth that are in function versus unerupted, developing teeth and single cell RNA-seq was carried out on jaw segments containing the dental forming tissues. In bulk RNAseq data, we found that functional teeth expressed genes involved in bone and tooth resorption. Indeed, we found expression of these markers in multinucleated odontoclasts within resorbing functional teeth. Chemotaxis genes SEMA3A and SEMA3E, were expressed within odontoblasts and in adjacent mesenchyme using RNAscope. Semaphorins could be involved in regulating odontoclast formation, recruitment or repulsion from developing teeth. The scRNA-seq experiment successfully isolated dental mesenchyme and several epithelial clusters. We confirmed that some of these genes are expressed in the earliest tooth buds within the tooth forming field and in erupting teeth. This work will lead to discovery of genes and cell populations that may have been gained or lost during evolution of amniotes. Moreover, gene differences may lead to dental therapies to prevent tooth loss from disease or injury.

overall_design: scRNA-seq

first: Joaquin

last: Henriquez

first: Katherine

last: Fu

first: Edward

middle: Z

last: Li

first: Joy

middle: M

last: Richman


title: Quantitative acetylomics reveals substrates of lysine acetyltransferase GCN5 in adult and aging Drosophila

status: Public on Dec 23 2022

city: Shanghai

first: Jingshu

address: 100 Hai Ke Rd., Pudong

institute: Chinese Academy of Sciences

summary: Drosophila GCN5 activity profoundly impacts gene expression.

overall_design: We conducted poly-A selected RNA-Seq experiments and explored the dynamics of gene expression during aging process (using heads and muscles of WT (5905) Drosophila at age of 3d, 15d, 30d, and 45d); We further conducted poly-A selected RNA-Seq experiments and explored the role of GCN5 on gene expression (using whole flies of WT (5905), gcn5 loss-of-function, and GCN5 overexpression Drosophila at age of 3d).

first: Huanhuan

last: Ma

first: Jing

last: Zhao


title: PTPN2 knockout vs WT

status: Public on Nov 30 2022

city: Denver

first: Pluto

last: Bio

address: 3575 Ringsby Ct Suite 414

institute: Pluto Bio

summary: We generated pluripotent stem cells (Mel1 hESC containing a GFP reporter driven by the endogenous  insulin promoter) with a functional knock out of PTPN2 by CRISPR/Cas9 genome editing. KO or WT control stem cells were differentiated into beta-like cells (sBC), sorted for GFP, and prepared for deep sequencing.

overall_design: PTPN2 KO and WT sBCs were GFP+ sorted and prepared for bulk RNA sequence analysis. RNA-seq pipeline and downstream analysis were performed using Pluto (https://pluto.bio).

first: Russ

last: Holger

first: Triolo

last: Taylor

first: Matuschek

last: Quinn


title: Transcriptomic and epigenomic analysis of germ-free and colitic mice

status: Public on Dec 12 2022

city: Philadelphia

first: Peder

last: Lund

state: PA

address: 3400 Civic Center Blvd, Smilow 9-176

institute: University of Pennsylvania

summary: The gut microbiota influences host epigenetics by fermenting dietary fiber into butyrate.  Although butyrate could promote histone acetylation by inhibiting histone deacetylases, it may also undergo oxidation to acetyl-CoA, a necessary cofactor for histone acetyltransferases.  Here, we find that epithelial cells from germ-free mice harbor a loss of histone H4 acetylation across the genome except at promoter regions.  Using stable isotope tracing in vivo with 13C-labeled fiber, we demonstrate that the microbiota supplies carbon for histone acetylation.  Subsequent metabolomic profiling revealed hundreds of labeled molecules and supported a microbial contribution to host fatty acid metabolism, which declined in response to colitis and correlated with reduced expression of genes involved in fatty acid oxidation.  These results illuminate the flow of carbon from the diet to the host via the microbiota, disruptions to which may affect energy homeostasis in the distal gut and contribute to the development of colitis.

overall_design: RNA-seq and ChIP-seq for H4ac4 were performed on colonic epithelial cells isolated from germ-free or conventional mice (n = 5 for RNA-seq, n = 2 for H4ac4 ChIP-seq and corresponding input chromatin).  The H4ac4 ChIP-seq included an exogenous spike-in of Drosophila chromatin for reference normalization.  RNA-seq was also performed on whole colon and cecal tissue from mice with or without DSS-induced colitis and treated with isotope-labeled or unlabeled inulin (n = 3).

first: Benjamin

middle: A

last: Garcia


title: In vitro culture model for high throughput screening of chemicals

status: Public on Dec 31 2022

city: Hershey

first: Yuka

last: Imamura Kawasawa

address: 500 University Dr.

department: College of Medicine, Pharmacology

institute: Penn State University

summary: To identify the pluripotency and the neural fate of two hiPSC-derived neural progenitor cell lines by evaluating their transcriptional profiles. We hereby report that the cells used in our study were progenitor cells of neural fate.

overall_design:
Total RNA of line AG09429 and single cell nuclear RNA of line GM03440 were sequenced and analyzed.
On July 31, 2024 the GEO Sample records, including all raw data and processed data, were replaced.

first: Ray

middle: Y

last: Ku

first: Ankush

last: Bansal

first: Seiji

last: Ishii

first: Toru

last: Sasaki

first: Nicolas

last: Ayvazian

first: Hye

last: Hwang

first: John

last: Peloquin

first: Yu

last: Shen

first: Keiji

last: Sugai

first: Diana

last: Vu

first: Masaaki

last: Torii

first: Kazue

last: Hashimoto-Torii


title: Diurnal rhythm-modulated transcriptome analysis of meibomian gland in hyperlipidemic mice using RNA sequencing

city: Hefei

first: Kan

last: He

address: 111 Jiulong Road

department: School of life sciences

institute: Anhui University

summary: Hyperlipidemia can induce the dysfunction of meibomian gland (MG) in mice, which may be affected by circadian rhythm. However, the underlying mechanism remains unclear. In this study, we exposed the hyperlipidemic mice model induced by four months feeding of high-fat diet to the regular light-dark cycles for two weeks. Then, phenotypic observation and RNA-seq of MG in experimental mice were performed to investigate the effect and transcriptional changes of hyperlipidemia and circadian rhythm on MG dysfunction. As a result, several significantly expressed genes and enriched pathways were identified to be associated with MG dysfunction in hyperlipidemic mice under circadian rhythms. High fat diet can not only bring hyperlipidemia, but also cause meibomian gland dysfunction, which is affected by rhythm genes. These data can provide us with a deeper understanding of the outcomes of MG altered by daily nutritional challenge.

overall_design: 6 to 8-week-old male C57BL/6 mice (purchased from Charles River Laboratories, Beijing, China) were housed under a 12-hour light/12-hour dark (LD) cycle. After adaptively fed for 1 week, the mice were randomly divided into two groups. The mice in the treatment group (the HF group) were fed with a high-fat diet (D12492, Xietong Pharmaceutical Bio-engineering Co. Ltd., Jiangsu, China; 60 kcal% fat) for 4 months, and the age-matched mice in the control group (the CT group,) were fed with a standard-fat diet (1010009, Xietong Pharmaceutical Bio-engineering Co. Ltd., Jiangsu, China; 10 kcal% fat) for 4 months. The mice in each group were sacrificed at different times (9 am, 3 pm, and 9 pm), the upper and lower eyelids were removed in whole to extract mRNA samples, and gene expression profiling was performed by high-throughput sequencing.

first: Jinxing

last: Su

first: Qing

last: Zhang


title: Osteocytes regulate skeletal senescence during development

status: Public on Nov 21 2022

first: Peng

last: Ding

address: No.600, Yishan Road

department: Orthopaedics

institute: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital

summary: As a part of the skeletal system, bone marrow environment also performs vital functions in maintaining the bone homeostasis. To gain an insight into the bone marrow environment change after osteocyte ablation, single cell RNA sequencing (scRNA-seq) was performed

overall_design: 13835 and 12727 bone marrow cells from WT and DTAhet mice respectively was isolated and analyzed using scRNAseq.

first: Junjie

last: Gao

first: Youshui

first: Chuan


title: Next generation sequencing of expression and differentially expression of miRNAs, lncRNAs and circRNAs in gastric adenocarcinoma

city: Yinchuan

first: Meng

last: Zhu

address: 1160 Shengli Street

institute: Ningxia Medical University

type: Non-coding RNA profiling by high throughput sequencing

summary: To systematically elaborate the transcriptomic landscape and complicated mechanism of gastric adenocarcinoma, we performed whole-transcriptome sequencing to screen miRNA, lncRNA, circRNA and mRNA expression profiles and the key functional ncRNAs were annotated.

overall_design: Human gastric cancer tissues and their corresponding non-tumorous adjacent tissues (≥5cm from cancer center) were collected from five patients who underwent gastrectomy at the Second Department of Surgical Oncology of General Hospital of Ningxia Medical University. Whole-transcriptome libraries were pooled and sequenced in a single lane of Illumina NovaSeq 6000 sequencing platform.

first: Ning

first: Jingwei

last: Ma


title: The Greatwall-Endosulfine switch accelerates autophagic flux during the cell divisions leading to G1 arrest and quiescence in fission yeast

status: Public on Nov 09 2022

city: Salamanca

first: Sergio

last: Moreno

email: smo@usal.es, ibfg_smp@usal.es

state: Salamanca

address: Zacarias Gonzalez 2

department: IBFG

country: Spain

institute: Institute of Functional Biology and Genomics (IBFG) (CSIC)

summary:
In fission yeast cell cycle exit, autophagy, G1 arrest and entry into quiescence are coordinated by the activity of the protein phosphatase PP2A/B55 through the Greatwall-Endosulfine switch.
In order to study the role of this pathway in the transcriptional changes that occur during entry into quiescence, RNA was extracted from wild-type cells and from four mutant strains at three time points.

overall_design: We performed a comparative gene expression profiling analysis of RNA-seq data between wild type cells growing in minimal medium (MM) and the mutants igo1∆, ppk18∆ cek1∆ and nmt1:GFP:ppk18+ and in minimal medium lacking nitrogen (MM-N) after 1 and 4 hours between wild type cells and the mutants igo1∆ and ppk18∆ cek1∆.

first: Alicia

last: Vázquez-Bolado

first: Rafael

last: López-San Segundo

first: Daniel

last: González-Ávarez

first: Belén

last: Suárez


title: Adult nucleus accumbens single-nucleus RNA-seq dataset for "Distinct subpopulations of D1 medium spiny neurons exhibit unique transcriptional responsiveness to cocaine"

status: Public on Jan 15 2023

city: Birmingham

first: Jeremy

middle: Jason

last: Day

state: AL

address: 1825 University Blvd

department: Neurobiology

institute: UAB

summary: This dataset contains single-nucleus RNA sequencing results from adult rat brain (nucleus accumbens) and serves as the basis for characterization of transcriptional response to repeated cocaine injections (20mg/kg, intraperitoneal injection). The goal of this experiment was to define the transcriptional response to repeated cocaine across distinct cell types in the nucleus accumbens. Single-cell sequencing was carried out with FACS-sorted nuclei isolated from these experiments using the 10X Genomics Chromium single cell sequencing platform.

overall_design: This experiment contains 4 biological samples. Samples were adult rat nucelus accumbens brain tissue isolated from rats 1hr after the final (7th) daily treatment with either saline or cocaine. Tissue was lysed to allow for nuclei collection via centrifugation. FACS-sorted nuclei were subject to 10X Genomics GEM generation and barcoding, GEM-RT cleanup and cDNA amplication, and library construction using a Chromium Single Cell 3ʹ Reagent Kit (v3 chemistry). Libraries underwent directional, paired-end PolyA+ RNA-seq on an Illumina Next-seq 500. Each sample has multiple raw fastq files, corresponding to different sequencing lanes (e.g., L001, L002, etc) and different reads (e.g., R1, R2). Additional index files are also provided for each sample and each lane (I1).

first: Robert

last: Phillps

first: Corey

middle: G

last: Duke

first: Jennifer

last: Tuscher

first: Morgan

last: Zipperly

first: Lara

last: Ianov


title: Vitamin D3 and deconvoluting a rash

city: Chicago

first: Kurt

middle: Q

last: Lu

state: IL

address: 303 E Chicago Ave

department: Dermatology

institute: Northwestern University

summary: To establish an expression profile of Nitrogen Mustard (NM) exposure-induced genes in healthy human skin and effect of VitD intervention. We further characterized a distinct intervention-independent response type in half of subjects after the 2nd NM exposure

overall_design: Differential expression analysis of bulk RNA-seq data from punch biopsies taken at 4 time points: Baseline, 72hrs post 1st NM-exposure, 72hrs post 2nd NM-exposure, and 6wks post 2nd NM-exposure, in 28 healthy patients, with 2 patients refusing the 4th punch biopsy resulting in n=110 samples. 14 patients were randomized to receive oral VitD 4 hours after initiation of 2nd NM exposure.

first: Spencer

middle: T

last: Evans

first: Madison

last: Ernst

first: José-Marc

last: Techner

first: Ummiye

middle: V

last: Onay

first: Dauren

last: Biyashev

first: Michael

last: Demczuk

last: Rothbaum

first: Luisa

middle: F

last: Christensen

first: Kord

last: Honda

first: Cuong

last: Nguyen

first: Thomas

last: McCormick

first: Lam

last: Tsoi

first: Johann

last: Gudjonsson

first: Kevin

middle: D

last: Cooper


title: Characterization of dynamic p300 enhancers in murine cardiomyocyte development [ChIP-seq]

first: Pingzhu

last: Zhou

summary: We report the application of bioChIP-seq, bulk RNA-seq, Hi-C, and Massively parallel reporter assays (MPRAs) to characterize the p300-bound regulatory regions in murine cardiomyocytes (CMs). By obtaining ChIP-seq data of coactivator p300 from seven developmental stages of mouse CMs, we defined the dynamic p300 enhancers from embryonic CMs to adult CMs. We then validated the activity of dynamic p300 enhancers with AAV9-based MPRAs, we found dynamic p300 enhancers show dynamic activity from postnatal day 0 (P0) CMs to 4-week-old CMs. In addition, MRPA results suggest nuclear receptor motifs are required for the activity of some p300 late enhancers. With Hi-C data of E12.5, P0 and adult CMs, we identified chromatin structure changes such as chromatin loops, compartment switch, and new TAD boundaries are associated with dynamic p300 binding. This study provides data source of CM-selective p300 enhancers, chromatin 3D structure and gene expression during CM development and maturation.

overall_design: Identification and characterization of p300 enhancers by CM-selective p300 bioChIP-seq and MPRAs.

first: Nathan

last: Vandusen

first: Yanchun

last: Zhang

first: William

last: Pu


title: Dual T cell– and B cell–intrinsic deficiency in humans

status: Public on Nov 07 2022

city: Doha

first: Nico

last: Marr

address: Education City

country: Qatar

institute: Hamad Bin Khalifa University

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

overall_design: Refer to individual Series


title: Molecular signatures of anthroponotic cutaneous leishmaniasis in the lesions of patients infected with Leishmania tropica

status: Public on Nov 01 2022

city: Tehran

first: Sima

last: Rafati

state: Tehran

address: Pasteur Ave

department: Immunotherapy and Leishmania Vaccine Research

country: Iran

institute: Pasteur Institute of Iran

summary: In this study employed a systems analysis approach to study molecular signatures of cutaneous leishmaniasis (CL)  caused by Leishmania tropica (L. tropica) in the skin lesions of ulcerativeCL (UCL) and non-ulcerative  CL( NUCL) patients.  Results from RNA-seq analysis determined shared and unique functional transcriptional pathways in the lesions of the UCL and Nucl patients. Several transcriptional pathways involved in inflammatory response were positively enriched in the CL lesions. These results enhance our understanding of human skin response to CL caused by L. tropica.

overall_design: The experiments were divided into three groups include; control, UCL, and NUCL patients groups.  A total of seven UCL and nine  NUCL patients were enrolled in the study. Healthy skin samples were taken from six volunteers. From each CL patient and healthy individual, two skin biopsies were collected. Comparative gene expression profiling analysis of RNA-seq data was performed for these groups.

first: Nasrin

last: Masoudzadeh

first: Malin

last: Östensson

first: Josefine

last: Persson

first: Vahid

last: Mashayekhi Goyonlo

first: Christopher

last: Agbajogu

first: Yasaman

last: Taslimi

first: Reza

last: Erfanian Salim

first: Farnaz

last: Zahedifard

first: Amir

last: Mizbani

first: Housein

last: MalekafzaliArdekani

first: Bronwyn

last: Gunn

first: Ali

last: Harandi


title: Epigenetic Mechanisms Regulating the Transcription of BBB Genes: Role of Wnt/β-catenin signaling

status: Public on Nov 03 2022

city: Houston

first: Peeyush Kumar

last: Thankamani Pandit

state: TEXAS

address: 6431 Fannin St,

department: Neurosurgery

institute: University of Texas Health Science Center Houston

summary:
To identify in CNS endothelial cell (EC) the gene cohorts that participate in blood brain barrier (BBB) formation versus maintenance. We investigated mechanisms behind the reduced Wnt/β-catenin signaling observed in adult CNS ECs
We also investigated whether the adult endothelial cells  can re express the EC gene cohorts required for the BBB formation.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for E-13.5 cortical ECs vs Adult Cortical ECs, vs Wnt3a (200nM) treated Adult cortical Ecs, Adult cortical ECs versus MS-275 (10uM) treated cortical ECs.

first: Peeyush

last: Kumar

first: Thankamani

last: Pandit


title: Total RNA-seq from Patient-Derived Xenograft models of Breast Cancer developed at Baylor College of Medicine

first: Michael

last: Lewis

state: TX

address: 1 Baylor Plaza N1210

department: Breast Center

institute: Baylor College of Medicine

summary: This study is a repository for all RNAseq data obtained from High Throuput Seqeuncing of Patient Derived Xenograft models of Breast Cancer studied at the Baylor College of Medicine Breast Center.

overall_design: Total RNA extracted from untreated xenograft tissue and sequenced using Illumina HiSeq/NovaSeq.

first: Susan

last: Hilsenbeck

first: Alana

middle: L

last: Welm

first: Bryan

middle: E

first: C

last: Osbourne

first: Aleksandar

last: Milosavljevic

first: Matthew

last: Ellis

first: Lacey

last: Dobrolecki

first: Jonathan

last: Lei

first: Varduhi

last: Petrosyan

first: Ramakrishnan

last: Rajaram Srinivasan

first: Chen

last: Huang

first: Suhas

last: Vasaikar

first: Christina

last: Sallas

first: Mothaffar

last: Rimawi

first: Alexander

middle: B

last: Saltzman

first: Anna

last: Malovannaya

first: Gerburg

last: Wulf

first: Daniel

last: Kraushaar

first: Tao

last: Wang

first: Xi

last: Chen

first: Gloria

last: Echevarria

first: Meenakshi

last: Anurag

first: Bing

last: Zhang


title: Epigenetic modules governing skin epidermal homeostasis

status: Public on Jan 13 2023

city: Bethesda

first: Stephen

middle: R

last: Brooks

address: 50 SOUTH DR, RM 1140

institute: NIAMS/NIH


title: DUSP6 mediates resistance to JAK2 inhibition and drives leukemic progression (RNA-Seq)

status: Public on Oct 25 2022

city: St. Louis

first: Tim

last: Kong

address: CSRB 8838

institute: Washington University School of Medicine

summary: Chronic myeloproliferative neoplasms (MPNs) exhibit a propensity for transformation to secondary acute myeloid leukemia (sAML), for which the underlying mechanisms remain poorly understood, resulting in limited treatment options and dismal clinical outcomes. Here, we performed bulk transcriptome profiling accompanied by single cell RNA-sequencing on CD34+ stem/progenitor cells from serial patient samples obtained at the chronic MPN and sAML phases, identifying aberrantly increased expression of dual-specificity phosphatase 6 (DUSP6) underlying disease transformation. Genetic and pharmacologic targeting of DUSP6 led to inhibition of S6 and JAK/STAT signaling, resulting in potent suppression of cell proliferation, while also reducing inflammatory cytokine production in primary samples. Furthermore, ectopic DUSP6 expression augmented proliferation and mediated JAK2 inhibitor resistance, while DUSP6 inhibition reduced colony-forming potential of JAK2 inhibitor-persistent patient cells. Mechanistically, DUSP6 perturbation dampened S6 signaling via inhibition of RSK1, which we identified as a second indispensable candidate associated with poor clinical outcome. Ectopic expression of DUSP6 in patient-derived xenograft (PDX) models exacerbated disease severity and led to early lethality, whereas DUSP6 knockdown suppressed leukemic engraftment. Finally, pharmacological inhibition of DUSP6 potently and specifically suppressed disease development across Jak2 V617F and MPL W515L MPN mouse models, as well as sAML PDXs, without inducing toxicity in healthy controls. These findings underscore DUSP6 in driving disease transformation and therapeutic resistance, and highlight the DUSP6-RSK1 axis as a novel, druggable pathway in myeloid malignancies.

overall_design: mRNA profiling of HEL cells treated with BCI, BI-D1870, or combination, and HEL JAK2 inhibitor persistent cells

last: Oh


title: Transcriptomic profiling of the adult reptilian dentition sheds light on the genes regulating indefinite tooth replacement

first: Stephane

last: Flibotte

address: 2370-6270 University Blvd.

institute: University of British Columbia

summary: The aim of this study is to discover new genes and cells involved in life-long tooth replacement. Here we study the adult dentition of the leopard gecko (Eublepharis macularius). Bulk RNAseq was used to compare teeth that are in function versus unerupted, developing teeth and single cell RNA-seq was carried out on jaw segments containing the dental forming tissues. In bulk RNAseq data, we found that functional teeth expressed genes involved in bone and tooth resorption. Indeed, we found expression of these markers in multinucleated odontoclasts within resorbing functional teeth. Chemotaxis genes SEMA3A and SEMA3E, were expressed within odontoblasts and in adjacent mesenchyme using RNAscope. Semaphorins could be involved in regulating odontoclast formation, recruitment or repulsion from developing teeth. The scRNA-seq experiment successfully isolated dental mesenchyme and several epithelial clusters. We confirmed that some of these genes are expressed in the earliest tooth buds within the tooth forming field and in erupting teeth. This work will lead to discovery of genes and cell populations that may have been gained or lost during evolution of amniotes. Moreover, gene differences may lead to dental therapies to prevent tooth loss from disease or injury.

overall_design: Comparative gene expression profiling analysis of bulk RNA-seq data for functional and developing teeth in adult leopard geckos.

first: Joaquin

middle: I

last: Henriquez

first: Katherine

last: Fu

first: Edward

last: Li

first: Joy

last: Richman


title: DUSP6 mediates resistance to JAK2 inhibition and drives leukemic progression

status: Public on Oct 24 2022


title: Polycomb repressive complexes 1 and 2 are each essential for maintenance of X inactivation in extraembryonic lineages

status: Public on Oct 12 2022

city: Yokohama

first: Osamu

last: Masui

address: 1-7-22 Suehirocho, Tsurumi

department: IMS

institute: RIKEN

summary: In female mammals, one of the two X chromosomes becomes inactivated during development by X-chromosome inactivation (XCI). Although Polycomb repressive complexes (PRC) 1 and PRC2 have both been implicated in gene silencing, their exact roles in XCI during in vivo development have remained elusive. To this end, we have studied mouse embryos lacking either PRC1 or PRC2. Here we demonstrate that the loss of either PRCs has a substantial impact on maintenance of gene silencing on the inactive X (Xi) in extraembryonic tissues, with overlapping yet different genes affected, indicating potentially independent roles of the two complexes. Importantly, a lack of PRC1 does not affect PRC2/H3K27me3 accumulation and a lack of PRC2 does not impact PRC1/H2AK119ub1 accumulation on the Xi. Thus PRC1 and PRC2 contribute independently to the maintenance of XCI in early post-implantation extraembryonic lineages, revealing that both Polycomb complexes can be directly involved and differently deployed in XCI.

overall_design: Allele-specific RNA-seq analysis of ectoplacental cones obtained from E7.5 control, ∆Ring1A/B and ∆Eed embryos

first: K

last: Nagao

first: T

last: Endo

first: O

first: F

last: Kezuka

first: C

last: Obuse

last: Corbel

first: E

last: Heard

first: H

last: Koseki


title: An atlas of healthy and injured cell states and niches in the human kidney [scRNA-Seq]

status: Public on Oct 10 2022

city: La Jolla

first: Kun

last: Zhang

state: California

address: 9500 Gilman Drive

institute: UCSD

summary: Understanding kidney disease relies upon defining the complexity of cell types and states, their associated molecular profiles, and interactions within tissue neighborhoods. We applied multiple single-cell or -nucleus assays (>400,000 nuclei/cells) and spatial imaging technologies to a broad spectrum of healthy reference (45 donors) and diseased (48 patients) kidneys. This has provided a high resolution cellular atlas of 51 main cell types that include rare and novel cell populations. The multi-omic approach provides detailed transcriptomic profiles, epigenomic regulatory factors, and spatial localizations spanning the entire kidney. We further define 28 cellular states across nephron segments and interstitium that were altered in kidney injury, encompassing cycling, adaptive or maladaptive repair, transitioning and degenerative states. Molecular signatures permitted localization of these states within injury neighborhoods using spatial transcriptomics, while large-scale 3D imaging analysis (~1.2 million neighborhoods) provided corresponding linkages to active immune responses. These analyses defined biological pathways relevant to injury time-course and niches, including signatures underlying epithelial repair that predicted maladaptive states associated with a decline in kidney function. This integrated multimodal spatial cell atlas of healthy and diseased human kidneys represents the most comprehensive benchmark of cellular states, neighborhoods, outcome-associated signatures, and publicly available interactive visualizations.

overall_design: Single nucleus RNA-Seq was performed on kidney (cortex, medulla) tissues from 3 Chronic Kidney Disease (CKD), and 2 healthy reference (Ref) individuals. This research was performed as part of a larger set of experiments for the Kidney Precision Medicine Project (KPMP) and the Human BioMolecular Atlas Program (HuBMAP).

first: Blue

last: Lake

first: Dinh

last: Diep

first: Amanda

last: Knoten

first: Sarah

last: Urata

first: Diane

last: Salamon

first: Joseph

middle: P

last: Gaut

first: Sanjay

last: Jain


title: Nanopore RNA sequencing in S. cerevisiae strains defective for decapping and deadenylation

status: Public on Oct 01 2022

city: Paris

first: Cosmin

last: Saveanu

address: 25 rue du docteur Roux

department: Genome and Genetic

country: France

institute: Institut Pasteur

summary: RNA turnover in eukaryotes is triggered by decapping, believed to be activated mostly after deadenylation. To investigate simultaneous changes in RNA levels and poly(A) tail size we performed Nanopore RNA sequencing on total RNA extracted from S. cerevisiae strains in which the decapping enzyme Dcp2, or the deadenylation factors Ccr4 and Pop2 were depleted through an inducible degron system. Two fully independent replicate experiments were performed for wild type and the two mutant conditions.

overall_design: Nanopore RNA-seq data from Dcp2_degron and CCR4-POP2_degron induced strains compared to the corresponding wild type BY4741 reference strain.

first: Léna

last: Audebert

first: Frank

last: Feuerbach

first: Laurence

last: Decourty

first: Abdelkader

last: Namane

first: Emmanuelle

last: Permal

first: Gwenael

last: Badis


title: An atlas of healthy and injured cell states and niches in the human kidney [SNARE-Seq2]

overall_design:
Single-nucleus chromatin accessibility and mRNA expression sequencing (SNARE-seq2 or SNARE2) performed on kidney (cortex, medulla) tissues from 7 healthy reference (Ref) individuals as part of the Human BioMolecular Atlas Program (HuBMAP)
>>> Submitter declares that the raw data are deposited in HuBMAP due to patient privacy concerns. <<<

first: Qiwen

last: Hu

first: Nongluk

last: Plongthongkum

first: Xin

last: Wang

first: Peter

last: Kharchenko


title: RNAs associated with Upf1, Pab1, Rpl16a, Lsm1 proteins in yeast

address: 25 rue Docteur Roux

institute: Pasteur Institute

summary: Nonsense mediated mRNA decay (NMD) is a translation-dependent surveillance pathway that eliminates RNAs with short open reading frames (ORFs) and long 3' untranslated regions (UTRs). Upf1 is the key protein of this degradation pathway and we were interested to purify the associated RNAs. Moreover we have done purifications of two proteins from the general mRNA turnover in yeast : Pab1 and Lsm1 that both bind RNAs poly(A) tails. We have also done a purification with a protein from the small ribosomal subunit (40S) in order to have a look at the translated RNAs.

overall_design: Upf1, Pab1, Rpl16a, Lsm1 associated RNAs

last: Ma


title: Transcriptomic analysis of mutant yeast strains deficient in Xrn1 nuclear import

status: Public on Sep 30 2022

city: Burjassot

first: Jose

middle: E.

last: Perez-Ortin

state: Valencia

address: Dr. Moliner 50

department: Bioquimica y Biologia Molecular

institute: Universitat de Valencia

type:
Expression profiling by array
Other

summary: The goal of the project was to study the transcription rates and mRNA levels, genome-wide, in several mutants in Xrn1 defetive in nuclear import. We used Genomic Run-On (GRO) experiment in wild type and xrn1 mutant strains.

overall_design: Cells were grown in YPD at 30ºC to 0.4-0.5 OD600. Cells were spun-down and collected. Note that each sample record represents three replicates .

first: José

last: Pérez-Ortín

last: García-Martínez


title: ChIP-seq of METTL4-mediated Nuclear N6-Deoxyadenosine Methylation Promotes Metastasis through Activating Multiple Metastasis-inducing targets

city: Taoyuang

first: Kou-Juey

last: Wu

state: Taiwan

address: No.15, Wenhua 1st Road, Gueishan Dist

department: Cancer Genome Research Center

country: Taiwan

institute: Chang Gung Memorial Hospital at Linkou

summary: Understanding the epigenome profiling of 6mA modification by METTL4, and HIF1 binding sites under hypoxia.

overall_design: Most of samples are 3 replicates. For IgG-ChIP-exo, HIF1 ChIP-seq only once.

first: Kai-Wen

last: Hsu

middle: C

last: Lai

first: Chuan

last: He


title: Single-cell transcriptome analysis of Terc KO bone marrow and brain

status: Public on Nov 18 2022

city: Shanghai

first: Junjie

last: Gao

address: 600 Yishan Road

institute: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

summary: Single-cell transcriptome analysis of 6-month Terc KO bone marrow and brain

overall_design: Examination of mouse bone marrow and brain

first: Changqing

last: Zhang


title: An atlas of healthy and injured cell states and niches in the human kidney [snCv3]

first: Kun

country: USA

overall_design:
Single nucleus RNA-Seq was performed on kidney (cortex, medulla, papilla) tissues from 13 Chronic Kidney Disease (CKD), 10 Acute Kidney Disease (AKI) and 13 healthy reference (Ref) individuals. This research was performed as part of the Kidney Precision Medicine Project (KPMP) and the Human BioMolecular Atlas Program (HuBMAP).
>>> Submitter declares that the raw data are deposited in KPMP and in HuBMAP due to patient privacy concerns. <<<

first: Blue

last: Lake

first: Dinh

last: Diep

first: Amanda

last: Knoten

first: Sarah

last: Urata

first: Diane

last: Salamon

first: Joseph

last: Gaut

first: Sanjay

last: Jain


title: The amniotic fluid proteome improves prediction of imminent delivery relative to quantitative cervical length: a cross-sectional study in women with a short cervix

status: Public on Sep 26 2022

city: Detroit

first: Adi

last: Tarca

state: MI

address: 3990 John R. St, 4 Brush South

institute: Wayne State University

summary:
For women identified as at risk for preterm birth attributable to a sonographic short cervix, the determination of imminent delivery is crucial for patient management. The current study aimed to identify amniotic fluid proteins that could predict imminent delivery in asymptomatic patients with a short cervix.
An aptamer-based multiplex platform was used to profile 1,310 AF proteins, and the significance of protein dysregulation was determined by moderated t-tests between women who destined to deliver within two weeks of amnicentesis.
The area under the receiver operating characteristic curve was calculated to determine whether protein abundance in combination with cervical length improved the prediction of imminent delivery after  amnicentesis as compared to cervical length alone.

overall_design: A cross-sectional study involving women who were diagnosed with a sonographic short cervix between 16 and 32 weeks of gestation and had a transabdominal amniocentesis performed within two days of the cervical length assessment.

first: Dereje

middle: W

last: Gudicha

first: Roberto

last: Romero

first: Nardhy

last: Gomez-Lopez

last: Galaz

first: Gaurav

last: Bhatti

first: Bogdan

last: Done

first: Eunjung

last: Jung

first: Dahiana

last: Gallo

first: Mariachiara

last: Bosco

first: Manaphat

last: Suksai

first: Ramiro

last: Diaz Primera

first: Piya

last: Chaemsaithong

first: Francesca

last: Gotsch

first: Stanley

middle: M

last: Berry

first: Tinnakorn

last: Chaiworapongsa


title: Human Plasma Proteome During Normal Pregnancy

summary: This study used SomaScan v 4.1 to profile>7000 proteins in maternal plasma and asses changes with gestational age and maternal characteristics. The study proposed models to estimate the expected protein abundance so that future datasets can be normalized agains these expected value to obtain Multiples of the Mean values.

overall_design: This is a longitudinal study that included typically 6 samples collected throughout gestation from women who had an uncomplicated pregnancy.