title: The transcription factor network of E. coli steers global responses to shifts in RNAP concentration

status: Public on Jun 07 2022

city: Tampere

first: Andre

middle: Sanches

last: Ribeiro

state: Pirkanmaa

address: Arvo Ylpön katu 34

department: Faculty of Medicine and Health Technology

country: Finland

institute: Tampere University

summary: The robustness and sensitivity of gene networks to environmental changes is critical for cell survival. How gene networks produce specific, chronologically ordered responses to genome-wide perturbations, while robustly maintaining homeostasis, remains an open question. We analysed if short- and mid-term genome-wide responses to shifts in RNA polymerase (RNAP) concentration are influenced by the known topology and logic of the transcription factor network (TFN) of Escherichia coli. We found that, at the gene cohort level, the magnitude of the single-gene, mid-term transcriptional responses to changes in RNAP concentration can be explained by the absolute difference between the gene’s numbers of activating and repressing input transcription factors (TFs). Interestingly, this difference is strongly positively correlated with the number of input TFs of the gene. Meanwhile, short-term responses showed only weak influence from the TFN. Our results suggest that the global topological traits of the TFN of E. coli shape which gene cohorts respond to genome-wide stresses.

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

overall_design: GSE178278 [poor media] Examination of genome-wide responses under various media dilution.

first: Bilena

last: L.B. Almeida

first: Mohamed

last: N.M. Bahrudeen

first: Vatsala

last: Chauhan

first: Suchintak

last: Dash

first: Vinodh

last: Kandavalli

first: Antti

last: Häkkinen

first: Jason

last: Lloyd-Price

first: Cristina

last: S.D. Palma

first: Ines

last: S.C. Baptista

first: Abhishekh

last: Gupta

first: Juha

last: Kesseli

first: Eric

last: Dufour

first: Olli-Pekka

last: Smolander

first: Matti

last: Nykter

first: Petri

last: Auvinen

first: Howard

last: T. Jacobs

first: Samuel

last: M.D. Oliveira

last: S. Ribeiro


title: The proto-oncogene DEK regulates neuronal excitability and tau accumulation in Alzheimer’s disease vulnerable neurons [chromatin]

status: Public on May 22 2022

city: Boston

first: Jean-Pierre

last: Roussarie

state: MA

address: 72 E Concord Street

department: Anatomy & Neurobiology

country: USA

institute: Boston University School of Medicine

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Neurons from layer II of the entorhinal cortex (ECII) are the first to accumulate tau protein aggregates and degenerate during prodromal Alzheimer’s disease. We used a data-driven functional genomics approach to model ECII neurons in silico that led us to the prediction that the proto-oncogene DEK is a driver of tau pathology in these neurons. In order to understand the function of DEK in vulnerable neurons, we modulated its expression in ECII neurons in vitro and in vivo in the mouse. Since DEK is a chromatin modulator, we investigated the genomic location of a few histone marks in DEK silenced cells using the CUT&TAG approach, as well as Chromatin Accessibility using ATAC-seq

overall_design: For the in vitro data, we generated primary neuron cultures of EC from mouse embryos at E17. At 7 days in vitro, we transduced the cultures with AAVs carrying shRNAs for DEK silencing (or the corresponding control non-targetting shRNA). 4 days post transduction, samples were harvested for CUT&TAG

first: Patricia

last: Rodriguez-Rodriguez

first: Christina

last: Tsagkogianni

first: Wei

last: Wang


title: The proto-oncogene DEK regulates neuronal excitability and tau accumulation in Alzheimer’s disease vulnerable neurons.

type: Expression profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: The proto-oncogene DEK regulates neuronal excitability and tau accumulation in Alzheimer’s disease vulnerable neurons [RNA-seq_invivo]

summary: Neurons from layer II of the entorhinal cortex (ECII) are the first to accumulate tau protein aggregates and degenerate during prodromal Alzheimer’s disease. We used a data-driven functional genomics approach to model ECII neurons in silico that led us to the prediction that the proto-oncogene DEK is a driver of tau pathology in these neurons. In order to understand the function of DEK in vulnerable neurons, we modulated its expression in ECII neurons in vitro and in vivo in the mouse. The present GEO entry corresponds to cell-type specific RNA-sequencing of ECII neurons in vivo 1 week after DEK silencing using AAV vectors.

overall_design: We injected ECII-bacTRAP mice stereotaxically with either control AAV or AAV expressing a small hairpin RNA directed against DEK. After 1 week, we lysed the entorhinal cortex (EC) from these mice, immunoprecipitated active polysomes, and then purified RNA for RNA-sequencing


title: A cellular hierarchy in melanoma uncouples growth and metastasis

status: Public on Jul 09 2022

city: leuven

first: Panagiotis

middle: Cristophe

last: Karras

state: belgium

address: Herestraat 49

country: Belgium

institute: VIB Center for Cancer Biology

summary: Although melanoma is notorious for its high degree of heterogeneity and plasticity, the origin and magnitude of cell state diversity remains poorly understood. Equally, it is not known whether melanoma growth and metastatic dissemination are supported by overlapping or distinct melanoma subpopulations. By combining mouse genetics, unbiased lineage tracing and quantitative modelling, single-cell and spatial transcriptomics, we provide evidence of a hierarchical model of tumour growth that mirrors the cellular and molecular logic underlying embryonic neural crest cell fate specification and differentiation. Our findings indicate that tumorigenic competence is associated with a spatially localized perivascular niche environment, a phenotype acquired through a NOTCH3-dependent intercellular communication pathway established by endothelial cells. Consistent with a model in which only a fraction of melanoma cells is fated to fuel growth, temporal single-cell tracing of a population of melanoma cells harbouring a mesenchymal-like state revealed that these cells do not contribute to primary tumour growth but, instead, constitutes a pool of metastatic-initiating cells that can switch cell identity while disseminating to secondary organs. Our data provide a spatially and temporally resolved map of the diversity and trajectories of cancer cell states within the evolving melanoma ecosystem and suggest that the ability to support growth and metastasis are limited to distinct pools of melanoma cells. The observation that these phenotypic competencies can be dynamically acquired upon exposure to specific niche signals warrant the development of therapeutic strategies that interfere with the cancer cell reprogramming activity of such microenvironmental cues.

sample_organism:
Homo sapiens
Mus
Mus musculus

platform_organism:
Homo sapiens
Mus
Mus musculus

overall_design: scRNA-Seq and bulk RNA-Seq

first: Florian

last: Rambow

first: Joanna

last: Pozniak


title: The Drosophila ZAD zinc finger protein Kipferl guides Rhino to piRNA clusters (sRNA-Seq)

status: Public on May 15 2022

city: Vienna

first: Lisa

last: Baumgartner

address: Dr. Bohr-Gasse 3

country: Austria

institute: IMBA

type: Non-coding RNA profiling by high throughput sequencing

summary:
RNA interference systems depend on the synthesis of small RNA precursors whose sequences define the target spectrum of these silencing pathways. The Drosophila Heterochromatin Protein 1 (HP1) variant Rhino permits transcription of PIWI-interacting RNA (piRNA) precursors within transposon-rich heterochromatic loci in germline cells. Current models propose that Rhino’s specific chromatin occupancy at piRNA source loci is determined by histone marks and maternally inherited piRNAs, but also imply the existence of other, undiscovered specificity cues.
Here, we identify a member of the diverse family of zinc finger associated domain (ZAD)-C2H2 proteins, Kipferl, as critical Rhino cofactor in ovaries. By binding to guanosine-rich DNA motifs and interacting with the Rhino chromodomain, Kipferl recruits Rhino to specific loci and stabilizes it on chromatin. In kipferl mutant flies, Rhino is lost from most of its target chromatin loci and instead accumulates on pericentromeric satellite arrays, resulting in decreased levels of transposon targeting piRNAs and impaired fertility. Our findings reveal that DNA sequence, in addition to the H3K9me3 mark, determines the identity of piRNA source loci and provide insight into how Rhino might be caught in the crossfire of genetic conflicts.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for MTD-Gal4 knock-downs of control, rhino and CG2678.

first: Dominik

last: Handler

first: Peter

last: Duchek

first: Sebastian

last: Platzer

first: Changwei

last: Yu

first: Julius

last: Brennecke


title: The Drosophila ZAD zinc finger protein Kipferl guides Rhino to piRNA clusters


title: The proto-oncogene DEK regulates neuronal excitability and tau accumulation in Alzheimer’s disease vulnerable neurons [RNA-seq_invitro]

summary: Neurons from layer II of the entorhinal cortex (ECII) are the first to accumulate tau protein aggregates and degenerate during prodromal Alzheimer’s disease. We used a data-driven functional genomics approach to model ECII neurons in silico that led us to the prediction that the proto-oncogene DEK is a driver of tau pathology in these neurons. In order to understand the function of DEK in vulnerable neurons, we modulated its expression in ECII neurons in vitro and in vivo in the mouse. The present GEO entry includes all of the data we collected from DEK-silenced and DEK-overexpressing ECneurons in vitro and in vivo.

overall_design: For the in vitro data, we generated primary neuron cultures of EC from mouse embryos at E17. At 7 days in vitro, we transduced the cultures with AAVs carrying shRNAs for DEK silencing (or the corresponding control non-targetting shRNA) or DEK cDNA for overexpression (or the corresponding empty control). 4 days post transduction, samples were harvested for RNAseq.


title: The Drosophila ZAD zinc finger protein Kipferl guides Rhino to piRNA clusters (RNA-Seq)


title: The Drosophila ZAD zinc finger protein Kipferl guides Rhino to piRNA clusters (ChIP-Seq)


title: Next Generation Sequencing and Quantitative Analysis of Mus musculus and Arvicanthis niloticus Olfactory Epithelium Transcriptomes

status: Public on May 01 2022

city: Zhunan, Miaoli County

first: Ben-Yang

last: Liao

address: 35 Keyan Rd.

department: Institute of Population Health Sciences

country: Taiwan

institute: National Health Research Institutes

summary: To quantify gene expression differences in olfactory epithelium between the mouse (Mus musculus) and the Nile rat (Arvicanthis niloticus), paired-end RNA sequencing (RNA-seq) was used to profile olfactory epithelium transcriptomes of six Nile rats and six mice (C57BL/6J) (one male and one female at the age of 8, 12, and 16 weeks for each species).

sample_organism:
Mus musculus
Arvicanthis niloticus

platform_organism:
Mus musculus
Arvicanthis niloticus

overall_design:
Olfactory epithelium mRNA profiles of 8-week, 12-week, 16-week old male and female mice (Mus musculus) (C57BL/67Narl) and Nile rats (Arvicanthis niloticus)

***Please note that processed data files have been updated on Aug 1, 2024****


title: Obesity disrupts innate-adaptive immune network patterning in adipose tissue

status: Public on Mar 10 2022

city: Ann Arbor

first: Lindsey

last: Muir

state: MI

address: 1600 Huron Parkway

institute: University of Michigan

summary: Obesity drives significant changes in adipose tissue that precede development of tissue and systemic insulin resistance. Immune cell infiltration and inflammation are known contributors to these changes but there is limited understanding of their spatial context tissue-wide. We sought to identify spatial patterning in epididymal adipose tissue immune cells in a time course of diet-induced obesity in mice. Using spatial transcriptomics and single-cell RNA-sequencing, we identified dominant cell type signatures preserved in their anatomical context, quantified gene expression patterns at spots throughout adipose tissue, performed cell type network analysis, and investigated ligand-receptor colocalization. Our data support increased innate immune cells, including macrophages, monocytes, and innate lymphoid cells, with tissue-wide interspersion and dampened adaptive immune cell signatures with obesity. Network analysis identified increased heterogeneity in all major immune cell types, consistent with increased subtypes. To capture tissue dynamics at obesity onset, we draw on mathematical principles from linear algebra and spectral graph theory. We provide a framework for better understanding cell cooperation toward emergence of multicellular tissue function. Further, we adapt Turing's mathematical theory on morphogenesis to show lapse of emergence in adipose tissue.

overall_design:
Paired spatial transcriptomics and single-cell RNA-sequencing data collected from contralateral epididymal white adipose tissue in mice fed a normal chow diet (0-weeks) or a high-fat diet for 8-weeks or 14-weeks. The normal diet spatial transcriptomics sample contains two replicates.

***Please note that the GSM5935796-GSM5935798 sample records have been updated with visium imaging and scale factors data on Aug 5, 2024****

first: Gabrielle

middle: A

last: Dotson

first: Indika

last: Rajapakse

first: Cooper

last: Stansbury


title: Tight gene co-expression between oocyte and surrounding cumulus is critical for oocyte developmental competence

status: Public on Mar 28 2022

city: Blacksburg

first: Fernando

last: Biase

state: VA

address: 175 W Campus Dr

department: Animal and Poultry Sciences

institute: Virginia Tech

summary: Cytoplasmic and nuclear maturation of oocytes as well as interaction with the surrounding cumulus cells are important features relevant to the acquisition of developmental competence. We used brilliant cresyl blue (BCB) to distinguish oocytes with low activity of the enzyme Glucose-6-Phosphate Dehydrogenase, and thus separated fully grown (BCB+) oocytes from those in the growing phase (BCB-). The BCB+ oocytes are twice as likely to produce a blastocyst in vitro compared to BCB- oocytes (P<0.01). We analyzed mitochondrial DNA (mtDNA) copy number in single oocytes and determined that BCB- oocytes have 1.3-fold more copies than BCB+ oocytes (P=0.004). We also interrogated the transcriptome of oocytes and surrounding cumulus cells of BCB+ versus BCB- oocytes. There was no differential transcript abundance of genes expressed in oocytes, but we identified 172 genes in cumulus cells with differential transcript abundance (FDR<0.05) based on the BCB staining of their oocyte. Differential gene co-expression analysis between BCB+ and BCB- oocytes and their surrounding cumulus cells revealed dynamic coordination of transcript abundance between both compartments of the cumulus-oocyte complex. We identified a subset of genes whose co-expression in fully grown oocytes (n=75) and their surrounding cumulus cells (n=108) compose a unique profile of the cumulus-oocyte complex. In conclusion, as oocytes transition from growing to fully grown, there is an increase in the likelihood of producing a blastocyst, a reduction of mtDNA copies and no systematic variation of transcript abundance. Cumulus cells present changes in transcript abundance, which reflects in a dynamic co-expression between oocyte and cumulus cells.

overall_design: Nineteen samples of cumulus oocyte complexes (COC) were classified as BCB + (n=09) or BCB- (n=10). From each COC we separated the oocyte and cumulus cells and sequence the transcriptome of each unit.

first: Biase

last: Fernando


title: The clinicopathological characteristics, prognosis and immune microenvironment mapping in MSI-H/MMR-D endometrial carcinomas

status: Public on Mar 09 2022

city: Shanghai

first: Yin

last: Liu

state: Shanghai

address: Building #2, 507 Zhengmin Road

department: Department of Laboratory Medicine

country: China

institute: Shanghai Pulmonary Hospital, Tongji University School of Medicine

summary: Endometrial cancer had a relatively high prevalence of MMR deficiency. MMR-D/MSI-H endometrial cancer patients are suggested to be potential beneficiaries of PD-1/PD-L1 inhibitor therapy. Here, we explored the prognostic value of MSI subtype in endometrial cancer and its correlation with immune environment. Based on expression and clinical data of 78 POLE, 123 MSI and 299 Other EC samples from the TCGA-UCEC project, we found that the MSI tumors were identified more often in early stage, had a lower age, better patient survival, enriched CD8+ T cells, and regulatory T cells and less M2 macrophages and activated dendritic cells than the Other group, and shared a relatively similar expression profile with POLE group by differential analysis. In addition, we established the immune landscape of an MMR-D endometrial cancer tissue using unbiased single-cell RNA-seq analysis of 3371 cells. By immunohistochemistry analysis, we found that the MMR-D tumors showed a higher trend of CD20+ B cells infiltration. Our study might expand our understanding of the role of immune subsets in MSI endometrial carcinomas and provide guidance of immunotherapy for endometrial cancer.

overall_design: Examination of immune cell infiltration in MSI-H/MMR-D endometrial carcinomas patient sample.

first: Yu-e

last: Guo


title: The aryl hydrocarbon receptor partially controls tissue adaptaion of intestinal eosinophils in mice

status: Public on Feb 25 2022

city: London

first: Nicola

middle: Laura

last: Diny

address: 1 Midland Rd

country: United Kingdom

institute: The Francis Crick Institute

summary: To determine how AHR affects eosinophil adaptation to the intestinal environment, eosinophils were sorted from the small intestine from WT, Ahr knockout and Ahrr knockout mice and compared by RNA sequencing. The canonical AHR pathway was active in murine intestinal eosinophils and limited eosinophil survival in the small intestine in a cell-intrinsic manner. Eosinophils from AHR-deficient mice retained increased expression of pathways associated with bone marrow eosinophils and failed to fully express the intestinal gene expression program, including extracellular matrix organization and cell junction pathways. Thus, our study demonstrates that the response to environmental triggers via AHR shapes tissue adaptation of eosinophils in the small intestine.

overall_design: RNA sequencing of eosinophils from the small intestine from WT, Ahr-KO and Ahrr-KO mice

first: Brigitta

last: Stockinger

first: Michael

last: Shapiro


first: Andre

last: Ribeiro

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

overall_design: GSE178279 [rich media] Examination of genome-wide responses under various media richness.

first: Bilena

last: L.B. Almeida

first: Mohamed

last: N.M. Bahrudeen

first: Vatsala

last: Chauhan

first: Suchintak

last: Dash

first: Vinodh

last: Kandavalli

first: Antti

last: Häkkinen

first: Jason

last: Lloyd-Price

first: Cristina

last: S.D. Palma

first: Ines

last: S.C. Baptista

first: Abhishekh

last: Gupta

first: Juha

last: Kesseli

first: Eric

last: Dufour

first: Olli-Pekka

last: Smolander

first: Matti

last: Nykter

first: Petri

last: Auvinen

first: Howard

last: T. Jacobs

first: Samuel

last: M.D. Oliveira

last: S. Ribeiro


first: Andre

last: Ribeiro

summary:
This SuperSeries is composed of the following SubSeries:
GSE178278	[poor media]
GSE178279	[rich media]
GSE197447	[poor media time lapse]

overall_design:
The overall design of each SubSeries is the following:
GSE178278	[poor media] Examination of genome-wide responses under various media dilution.
GSE178279	[rich media] Examination of genome-wide responses under various media richness.
GSE197447	[poor media time lapse] Examination of genome-wide responses under various media dilution over time.


title: RNA sequencing of wild Type, Rictor-KO or GATA3-KO J774.1 cells

status: Public on Feb 15 2022

city: Tokushima

first: kohta

last: ohnishi

address: Kuramoto-cho 3-18-15

country: Japan

institute: Tokushima University

summary: Purpose: Endosomal-lysosomal system is one of the pivotal degradation system for a varieties of extracellular substances, of which dysfunction has been indicated to be associated with cardiovascular and neurodegenerative diseases. This degradation process consists of multiple steps; uptake of extracellular molecules, endosomal formation and its transportation to lysosomes, and digestion by lysosomal enzymes. Whereas TFEB, is a transcriptional factor, has been well studied as a master regulator of cellular uptake and lysosomal function, a key regulatory mechanism for endosomal maturation remains unclear. We previously found that isorhamnetin, a dietary flavonoid, enhanced the endosomal-lysosomal proteolysis in J774.1 macrophage-like cell line, which was independent on mTORC1-TFEB axis. In this study, we analyzed the molecular mechanism of activated endosomal-lysosomal degradation by isorhamnetin.

overall_design: mRNA profiles of wild type, rictor-KO or GATA3-KO J774.1 treated with isorhamnetin

first: Maiko

last: Sakai

first: Kohta

last: Ohnishi


title: Modulations of mTORC2-GATA3 is by isorhamnetin activates endosomal-lysosomal degradation in J774.1 macrophage-like cell line


title: The transcription factor network of E. coli steers global responses to shifts in RNAP concentration

overall_design: GSE197447 [poor media time lapse] Examination of genome-wide responses under various media dilution over time.

first: Bilena

last: L.B. Almeida

first: Mohamed

last: N.M. Bahrudeen

first: Vatsala

last: Chauhan

first: Suchintak

last: Dash

first: Vinodh

last: Kandavalli

last: Häkkinen


title: scRNAseq in Dbh-iCre;LSL-MYCN mouse model of neuroblasoma

status: Public on Apr 10 2023

city: MEMPHIS

first: Richard

last: Chapple

state: Tennessee

address: 262 Danny Thomas Pl

institute: St Jude Children's Hospital

summary: The initiation of drug response in neuroblastoma was assessed using this genetically engineered mouse model.  scRNAseq was employed to determine the heterogeneity of the initial transcriptional response to the common chemotherapeutic drug, cisplatin.

overall_design: Adrenal neuroblastoma tumors from cisplatin- (2mg/kg) or vehicle-treated mice were collected after 24 hours of treatment.  Single cell suspensions were obtained through dissociation, and were subjected to scRNAseq using the 10X Genomics platform.

first: Paul

last: Geeleher

first: Sivaraman

last: Natarajan

first: John

last: Easton


title: Chidamide inhibits double expressor lymphoma through repressing Myc expression and activity

status: Public on Apr 24 2022

city: Xi’an, China

first: lei

last: zhao

state: Shaanxi

address: Youyixi Road 21

department: School of Ecology and Environment

institute: Northwestern Polytechnical University

summary: Double-expressor lymphoma (DEL), defined by MYC and BCL-2 overexpression without corresponding chromosome translocations, is often associated with poor outcomes for standard treatment (R-CHOP). Recently, inhibitors of histone deacetylases have shown great effect in T cell lymphomas. However, its effects on B cell lymphomas are mild. Here, our clinical retrospective analysis showed that HDAC inhibitor chidamide combined with R-CHOP (CR-CHOP) can dramatically increase the complete remission rate of patients with DEL. And the sensitivity of B cell lymphoma cell lines to chidamide is negatively correlated to Myc level. From Western blots and transcriptomics analysis, we found that chidamide treatment could reduce Myc protein level and downregulate the transcription levels of corresponding Myc downstream targets. Thus our results indicate that HDAC inhibitor chidamde holds great potential for treating DEL, which likely functions through inhibiting the Myc pathway.

overall_design: Bulk RNA-seq of JeKo-1/Granta-519 lymphoma cell line treated with Chidamide or vehicle

first: Jianjun

last: Li

first: Xiaohang

last: Hang

first: Pengpeng

last: Liu

first: Lei

last: Zhao

first: Ting

first: Yu


title: TSA Breast Cancer Wild-type or RIPK1 Deletion Tumors Single-Cell RNA Sequencing Data for CD45+ and CD45- Cell Types

status: Public on Feb 07 2022

city: Philadelphia

first: Jingya

last: Qiu

state: PA

address: 421 Curie Blvd, 532

department: Radiation Oncology

institute: University of Pennsylvania

summary: We found that expression of RIPK1 by cancer cells drives resistance to immune checkpoint blockade therapy. The goal of this study was to evaluate the effects of deletion of RIPK1 in the cancer cells on the tumor immune microenvironment by using single-cell RNA sequencing to evaluate defining transcriptomic features of immune subsets in the tumor microenvironment, as well as to look at corresponding gene expression changes in the immune and non-immune subsets upon RIPK1 deletion. Wild-type (WT) tumors were sequenced as a control and gene expression patterns were compared to tumors derived from RIPK1 knockout (KO) cancer cells.

overall_design: Two tumors each derived from wild-type (WT) and RIPK1 knockout (KO) cancer cells were harvested and sorted into either CD45+ or CD45- samples, thus 8 samples were prepared consisting of two replicates of either wild-type derived or RIPK1 KO derived tumors for CD45+ and CD45- populations.

first: Andy

middle: J

last: Minn

first: Lisa

last: Cucolo


title: Patient-Derived Liver on Chips

status: Public on Jan 24 2022

first: Jonathan

last: Sexton

address: 1150 W. Medical Center Dr., RM 4742F

institute: University of Michigan, Ann Arbor

summary: iPSCs were differentiated to human liver organoids as previously described. Human liver organoids were dispersed into single-cell suspension with trypsin (0.25%) and transferred to both channels in an dual-channel organ on chip system and cultured in hepatocyte maturation media. Media flow was regulated to 30 µL/hr for both channels. After 7 days of culture, liver chips were treated with vehicle control, or DILI-related compounds APAP, FIAU, tenofovir, or a tenofovir-inarigivir combination. scRNA sequencing was performed on intact HLOs and liver chips treated with each condition to compare HLOs pre- and post-chip and provide mechanistic DILI insight of treatments. Each sample generated between 440 and 860 million barcoded reads corresponding to an estimated 4,600 to 25,000 cells per sample

overall_design: Liver chip transcriptomic profile with DILI compound perturbations.

middle: Z

first: Charles

last: Zhang

first: Matthew

last: O'Meara

first: Sophia

middle: R

last: Meyer


title: BRD4 marks chromatin on cell cycle genes activates their transcription and orchestrates mitotic cell division

status: Public on Jan 31 2022

city: New York

first: Mahesh

last: Bachu

email: bmahesh07@gmail.com, bachum@hss.edu

state: New York

address: 535 E 70th St 6th Floor

institute: Hospital For Special Surgery

overall_design: Examination of BRD4 occupancy at variuos stages of cell cycle in mouse embryonic fibroblasts (MEFs)

first: Tiyun

last: Wu


title: Computational frameworks for predicting protein interactions via single-cell proximity sequencing

city: Chicago

first: Hoang Van

last: Phan

state: Illinois

address: 5640 S Ellis Ave

department: Priztker School of Molecular Engineering

institute: The University of Chicago

summary: Proximity sequencing (Prox-seq) is a method that can simultaneously measure gene expression, protein abundance and protein complex information in single cells. By making use of proximity information from proteins, Prox-seq can infer surface protein complexes at the single-cell level. Previously, we proposed a statistical method for predicting protein complex abundance in single cells from Prox-seq data. However, it is difficult to experimentally validate the prediction results. Here, we first introduces a physical model which enables simulation of Prox-seq data. The simulated data is then used to validate the statistical method that we proposed previously, and to understand how protein abundance can influence protein complex prediction. Second, we propose a modification to Prox-seq, and use the new measurements from the modification to develop a second, independent method for predicting protein complexes. We demonstrate that on experimental data, the two methods generally agree with each other, with the second method generally producing more accurate protein complex abundance results. Thus, we present a simple way to investigate the behavior of Prox-seq data under various biological conditions, and independent methods for predicting and quantifying protein complexes.

overall_design: Prox-seq analysis of single Jurkat and Raji cells using plate-based pipeline

first: Hoang

middle: V


title: Identifying the Interaction of the Brain and the Pituitary in Social- and Reproductive- State of Tilapia by Transcriptome Analyses

status: Public on Apr 30 2022

city: rehovot

first: Berta

last: Levavi-Sivan

state: Israel

address: Hertzel

department: Animal sciences

country: Israel

institute: The Hebrew University of Jerusalem

summary: Introduction: reproduction in fish, as in all vertebrates, is regulated by GnRH control on gonadotropic hormones (GTH) activity. However, the neuroendocrine factors that promote GnRH and GTH activity are unknown. In Nile tilapia (Oreochromis niloticus), sexual activity and the ability to reproduce depend on social rank; only dominant males and females reproduce. Here, this characteristic of dominant fish allows us to compare brain and pituitary gene expression in animals that do and do not reproduce, aiming to reveal mechanisms that regulate reproduction. Methods: an extensive transcriptome analysis was performed, combining two sets of transcriptomes: a novel whole-brain and pituitary transcriptome of established dominant males identified by behavioral assays, together with a cell-specific transcriptome of LH and FSH cells. Results: in most dominant fish, as determined behaviorally, the gonadosomatic index (GSI) was higher than in subordinate fish, and the leading upregulated pituitary genes were those coding for GTHs. In the brain, various neuropeptide genes, including oxytocin, cholecystokinin, and MCH, were upregulated; these may be related to reproductive status through effects on behavior and feeding. In a network analysis combining the two transcriptome sets, brain aromatase (cyp19a1b), which is specifically expressed in LH cells, is the most central gene with the highest number of connections. Conclusions: the close correlation between behavioral dominance and reproductive capacity in tilapia allows us to unravel novel genes that may partake in the regulation of the HPG axis, highlighting aromatase as an important factor in integrating the brain and pituitary factors that maintain a sexually active organism.

overall_design: Brain and pituitary RNA-seq of dominanat reproducing vs subordinate non reproducing male tilapia

first: Lian

last: Hollander-Cohen

first: Miriam

last: Shulman


title: J774.1 mouse macrophage-like cell line: Control vs. IR or TAM or Torin1

first: kohta

last: ohnishi

summary: Transcriptional profiling of J774.1 cells comparing control (DMSO treatment) with IR or TAM or Torin1 treated cells.

overall_design: Four-condition experiment, Ctrl. vs. IR vs. TAM vs. Torin1. Biological replicates: 2

first: Maiko

last: Sakai

first: Kohta

last: Ohnishi


title: The immunological comparison of control PDA tumors and Krt19-edited PDA tumors

status: Public on Jan 07 2022

city: Cold Spring Harbor

first: Zhikai

last: Wang

state: NY

address: 1 Bungtown Road

institute: Cold Spring Harbor Laboratory

summary: Our studies indicate that cancer cells of carcinomas are coated with CXCL12 chemokine in covalent conjugation with keratin-19 (KRT19). Murine pancreatic ductal adenocarcinomas (PDA) formed with Krt19-edited cancer cells lack the CXCL12-coating and are infiltrated with T cells, compared to tumors formed with control sgScramble PDA cells. To probe the immunological role of this CXCL12-coating thoroughly, bulk RNA sequencing of subcutaneous (s/c) murine sgScramble PDA tumors and Krt19-edited PDA tumors were conducted.

overall_design: sgScramble PDA tumors vs sgKrt19 PDA tumors

first: Douglas

middle: T

last: Fearon


title: MUC1-C DICTATES JUN AND BAF-MEDIATED CHROMATIN REMODELING AT  PROMOTER AND ENHANCER SIGNATURES IN CANCER STEM CELLS

status: Public on Jan 19 2022

city: Buffalo

first: Tao

last: Liu

address: Elm and Carlton St

department: Biostatistics and Bioinformatics

institute: Roswell Park Comprehensive Cancer Institute

summary: We report the application of ATAC-seq to study the role of MUC1-C in chromatin remodeling in cancer stem cells

overall_design: ATAC-seq was done in one Prostate cancer cell line DU-145 and TNBC cell line BT-549  in the presence and absence of MUC1-C protein

first: Atrayee

last: Bhattacharya

first: Donald

last: Kufe


title: Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism

status: Public on Apr 05 2022

city: Manchester

first: Polly

last: Downton

address: Oxford Road

institute: University of Manchester

summary: Chronic inflammation underpins many human diseases. The morbidity and mortality of chronic inflammation is often mediated through metabolic dysfunction. Inflammatory and metabolic processes vary through circadian time, suggesting an important temporal cross-talk between these systems. Here, we show that inflammatory arthritis results in rhythmic joint inflammation and drives major changes in muscle and liver energy metabolism and rhythmic gene expression.

overall_design: RNA-Seq from mRNA of mouse liver, muscle and joint across the course of a day. Time-series include mRNA profiles from DBA/1 mice with collagen-induced arthritis (CIA) on day 7 after the development of disease symptoms and also at matched time points in naïve control mice.

first: Fabio

last: Sanna

first: Robert

last: Maidstone

first: Toryn

middle: M

last: Poolman

first: Edward

last: Hayter

first: Suzanna

middle: H

last: Dickson

first: Nick

last: Ciccone

first: James

middle: O

last: Early

first: Antony

last: Adamson

first: David

middle: G

last: Spiller

first: Devin

last: Simpkins

first: Matthew

last: Baxter

first: Roman

last: Fischer

first: Magnus

last: Rattray

first: Andrew

middle: S

last: Loudon

first: Julie

middle: E

last: Gibbs

last: Bechtold

middle: W

last: Ray


title: RNA-sequencing data of intestinal tissue of mice adminstered proanthocyanidins (PAC) and infected with Trichuris muris (Tm)

status: Public on Jan 01 2022

city: Frederiksberg C

last: Williams

state: --- Select One ---

address: Dyrlægevej 100

country: Denmark

institute: University of Copenhagen

summary: We show here the transcriptional response in the  caecum of mice infected with Tm with or without concurrent PAC administration

overall_design: RNA was obtained from the tissue of 8 mice gavaged with water and uninfected, 5 mice gavaged with PAC and infected with Tm, and 8 mice gavaged with water and infected with Tm, and 8 uninfected mice gavaged with PAC.


title: RNA-sequencing data of intestinal tissue of mice administered proanthocyanidins (PAC) and infected with Heligomosomoides polygyrus (Hp)

summary: We show here the transcriptional response in the  small intestine of mice infected with Hp with or without concurrent PAC administration

overall_design: RNA was obtained from the tissue of 5 mice gavaged with water and uninfected, 5 mice gavaged with PAC and infected with Hp, and 5 mice gavaged with water and infected with Hp


title: ScRNA-seq of cell fractions from LNs of CCL17-competent  and CCL17-deficient mice on chew diet and western diet

status: Public on Apr 18 2022

city: Munich

first: Christian

last: Weber

address: Pettenkoferstreet 8a and 9

country: Germany

institute: Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich

summary: The deficiency in CCL17 decreased atherosclerotic plaque burden by facilitating Treg maintenance and survival. cDC-derived CCL17 plays a crucial role in the recruitment and migration of various T cell subsets, including a subpopulation of CD4+ T cells, regulatory T cells (Tregs).  To evaluate whether CCL17-deficient cDCs harbor an unique expression profile. we FACS-sorted CD45+CD11c+CD3-CD19- cells from lymph nodes (LNs) of Apoe-/-Ccl17wt/e or Apoe-/-Ccl17e/e mice on chew diet (CD) and performed single cell RNA sequencing (scRNAseq). We also performed scRNAseq to detect the expression of some chemokine receptors in sorted CD45+CD19-MHC+ cells from aortic LNs of Apoe-/-Ccl17wt/e or Apoe-/-Ccl17e/e mice on 6-week western diet (WD).

overall_design: We performed scRNAseq of FACS-sorted CD45+CD11c+CD3-CD19- cells from pooled LNs of Apoe-/-Ccl17wt/e (Het) or Apoe-/-Ccl17e/e (Hom) mice on CD and FACS-sorted CD45+CD19-MHCII+ cells from aortic LNs of Het or Hom mice on 6-week WD.

first: Yi

last: Yan

first: Yvonne

last: Döring

first: Changjun

last: Yin

first: Xi

last: Zhang

last: Jansen

first: Michael

last: Hristov

first: Inhye

last: Park

first: Claudia

last: Monaco


title: Transcripitional profiling of Huh7 cells after MAT2A inhibitor (FIDAS-5) or BET bromodomain inhibitor (JQ1) treatment

status: Public on Feb 28 2022

first: Jinyang

last: Li

address: 1230 York Ave

institute: The Rockefeller University

summary: RNA-seq analysis of Huh7 cells after MAT2A inhibitor (FIDAS-5) or BET bromodomain inhibitor (JQ1) treatment. The analysis revealed that inhibition of MAT2A or BET factors suppresses the expression of genes regulating cell cycle progression and additional cellular programs.

overall_design: The aim of this project is to compare the transcriptome of human hepatocellular carcinoma cells Huh7 with or without MAT2A inhibitor FIDAS-5 or BET inhibitor JQ1 treatment by RNA-seq. Huh7 cells were cultured in DMEM with 10% FBS, then treated with 5 uM FIDAS-5 for 48 hour or 0.5 uM JQ1 for 48 hour.

first: Fuming


title: A human DNA methylation atlas reveals principles of cell type-specific methylation and identifies thousands of cell type-specific regulatory elements

status: Public on Mar 02 2022

city: Jerusalem

first: Tommy

last: Kaplan

address: Givat Ram Campus

department: School of Computer Science and Engineering

institute: Hebrew University

type: Methylation profiling by high throughput sequencing

summary: DNA methylation is a fundamental epigenetic mark that governs chromatin organization, cell identity, and gene expression. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing of 39 cell types sorted from 205 healthy tissue samples.  Replicates of the same cell type are >99.5% identical, demonstrating robustness of cell identity programs to genetic variation and environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny, and identifies methylation patterns retained since gastrulation. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely methylated loci are rare and are enriched for CpG islands, polycomb targets, and CTCF binding sites, suggesting a role in shaping cell type-specific chromatin looping. The atlas provides an essential resource for interpretation of disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.

overall_design:
To portray the genome-wide patterns of DNA methylation across a variety of cell types, we obtained 205 samples of freshly isolated healthy adult tissue samples from 137 consented donors undergoing a variety of surgical procedures (ages 3-83). We dissociated tissue samples into single cell suspensions, and used lineage-specific antibodies to cell type specific surface markers to FACS purify cell populations covering 39 primary cell-types. The purity of cell types was confirmed using RT-qPCR for cell type specific gene expression markers, and assessing known tissue-specific methylation markers when possible (Methods, Supplemental Fig. S1). We then subjected cell type-specific genomic DNA to WGBS and sequenced at a mean depth of >30X, using 150bp-long paired-end reads, with an average fragment size of 174bp.

**Raw fastq files are available at the European Genome-phenome Archive (EGA) under study accession number: EGAS00001006791**

Please note that the records have been updated with the processed data generated with the *hg38* reference on May 17, 2022.

Please note that the GSM6810003-GSM6810048 records have been updated with the processed data generated with the *hg38* reference on Aug 20, 2024

first: Netanel

last: Loyfer

first: Judith

last: Magenheim

first: Ayelet

last: Peretz

first: Gordon

last: Cann

first: Joerg

last: Bredno

first: Agnes

last: Klochendler

first: Ilana

last: Fox-Fisher

first: Sapir

last: Shabi-Porat

first: Merav

last: Hecht

first: Tsuria

last: Pelet

first: Joshua

last: Moss

first: Hamed

last: Amini

first: Patriss

last: Moradi

first: Sudharani

last: Nagaraju

first: Dvora

last: Bauman

first: David

last: Shveiky

first: Shay

last: Porat

first: Gurion

last: Rivkin

first: Omer

last: Or

first: Nir

last: Hirshoren

first: Einat

last: Carmon

first: Alon

last: Pikarsky

first: Abed

last: Khalaileh

first: Gideon

last: Zamir

first: Ronit

last: Grinbaum

first: Machmud

last: Abu Gazala

first: Ido

last: Mizrahi

first: Noam

last: Shussman

first: Amit

last: Korach

first: Ori

last: Wald

first: Uzi

last: Izhar

first: Eldad

last: Erez

first: Vladimir

last: Yutkin

first: Yaacov

last: Samet

first: Devorah

last: Rotnemer Golinkin

first: Kirsty

middle: L

last: Spalding

first: Henrik

last: Druid

first: Peter

last: Arner

first: A

last: Shapiro

first: Markus

last: Grompe

first: Alex

last: Aravanis

first: Oliver

last: Venn

first: Arash

last: Jamshidi

first: Ruth

last: Shemer

first: Yuval

last: Dor

first: Benjamin


title: Single-cell RNA-sequencing of mouse islets exposed to proinflammatory cytokines [18hrs]

status: Public on Dec 20 2021

first: Weiguo

last: Cui

state: IL

address: 303 E Chicago Ave

department: Pathology

institute: Northwestern University

summary: Exposure to proinflammatory cytokines is believed to contribute to pancreatic β-cells during diabetes development.  While some cytokine-mediated changes in islet gene expression are known, the heterogeneity of the response is not well-understood. Following 18 hour treatment with interleukin-1 beta (IL-1β) and interferon-gamma (IFN-γ) alone or together, mouse islets were subjected to single-cell RNA-sequencing (scRNA-seq). Inducible nitric oxide synthase (iNOS) mRNA (Nos2), antiviral genes, and immune-associated genes were induced in a subset of β-cells in response to both cytokines, while IL-1β alone activated only antiviral genes. Subsets of α- and δ-cells expressed Nos2 and exhibited similar gene expression changes as β-cells, including induction of antiviral genes and repression of identity genes. Finally, cytokine-responsiveness was inversely correlated with expression of genes encoding heat shock proteins. Our findings show that all endocrine cell types respond to cytokines, IL-1β induces the expression of protective genes in β-cells, and cellular stress gene expression is associated with an inhibition in cytokine signaling.

overall_design: Four samples of murine islets (no cytokine treatment, IL-1β and IFNγ only, IL-1β and IFNγ with NMMA, NMMA only exposure for 18 hours) were prepared using 10x Genomics Chromium platform

first: John

last: Corbett

first: Jennifer

last: Stancill


title: Immunophenotyping of Acute Inflammatory Exacerbations of Lung Injury Driven by Mutant Surfactant Protein-C: A Role for Inflammatory Eosinophils

city: Salt Lake City

first: Alessandro

last: Venosa

state: UT

department: Pharmacology and Toxicology

institute: University of Utah

summary: Acute inflammatory exacerbations (AIEs) represent immune-driven deteriorations of many chronic lung conditions, including COPD, asthma, and pulmonary fibrosis (PF). The first line of therapy is represented by broad-spectrum immunomodulation. Among the several inflammatory populations mobilizing during AIEs, eosinophils have been identified as promising indicators of an active inflammatory exacerbation. To better study the eosinophil-parenchymal crosstalk during AIE-PF, this work leverages a clinically relevant model of inflammatory exacerbations triggered by mutation in the alveolar epithelial type 2 cell Surfactant Protein-C gene [SP-CI73T]. Unbiased single-cell sequencing analysis of controls and SP-CI73T mutants at a time coordinated with peak eosinophilia (14 d) defined heightened inflammatory activation, chemotaxis, and survival signaling (IL-6, IL-4/13, STAT3, Glucocorticoid Receptor, mTOR, and MYC) in eosinophils. To study the impact of eosinophils in inflammatory exacerbations, the SP-CI73T line was crossed with eosinophil lineage deficient mice (GATA1Δdbl, SP-CI73TGATA1KO). Time course analysis (7-42 d) demonstrated improved lung histology, survival, and reduced inflammation in SP-CI73TGATA1KO cohorts. Spectral flow cytometry of tissue digests confirmed eosinophil depletion in GATA1KO mice and the absence of a compensatory shift in neutrophils and immature monocyte recruitment. Eosinophil deletion was seen to boost accumulation of total monocyte-derived macrophages, 14 d post-injury, while declines in CD3+CD4+ lymphocyte abundance observed during SP-CI73T-induced injury were limited in SP-CI73TGATA1KO mice. Histochemical analysis 14 d post-injury revealed atypical inflammatory cell activation in SP-CI73TGATA1KO mice, with reduced numbers of Arg-1+ and iNOS+ cells, but increases in mcp1 and tgfb1 mRNA expression in BAL cells and tissue. To study corticosteroid efficacy in highly eosinophilic exacerbations, SP-CI73T mice received dexamethasone (1 mg/kg daily, i.p) starting 5 d post-induction. Dexamethasone successfully reduced total and eosinophil (CD11b+SigF+CD11c-) counts at 14 d and was linked to reduced evidence of structural damage and perivascular infiltrate. Together, these results illustrate the deleterious role of eosinophils in inflammatory events preceding lung fibrosis and demonstrate the efficacy of corticosteroid treatment in highly eosinophilic exacerbations induced by mutant SP-CI73T.

overall_design: Single cell sequentinc of collagenase digested lung tissue from SP-C mutant mice at steady state and 14 d post injury

first: Sophie

last: Cowman


title: Characterization of effects of estrogen, progesterone and the endocrine-disrupting chemicals on mouse mammary gland in 4-vinylcyclohexene diepoxide-induced menopause model via single-cell RNA-sequencing

status: Public on Feb 08 2022

city: Duarte

first: wei

last: chen

state: CA

address: 1500 E Duarte Rd

department: Cancer Biology-BRI

institute: City of Hope National Medical Center

summary: Mammary gland is a dynamic organ which undergoes most of its structural development after birth under cyclic control of ovarian hormones such as estrogen and progesterone. Using 4-vinylcyclohexene diepoxide (VCD) menopause model, we investigated the effect of ovarian hormones on mouse mammary glands. In particular, we focused on mouse mammary gland fibroblasts because they are one of the known crucial players but yet to be characterized well. With integrated analysis including six other publicly available datasets as well as mammary epithelium atlas data, we comprehensively described the characters of mouse mammary gland (e.g. potential commitment to mammary gland development, response to estrogens, developmental relationship, and crosstalk with mammary epithelium) in a population specific manner. Furthermore, we investigated the effect of endocrine disrupting chemical named polybrominated diphenyl ethers (PBDEs) in either of absence or presence of ovarian hormones on whole cellular components of mouse mammary gland including epithelial cells, fibroblasts, and immune cells at a single cell level.

overall_design: Female 9-weeks-old C57BL/6 mice were administered with VCD for 15 days. At 100 days after starting the VCD administration, when menopause is accomplished by complete ovarian failure, the mice were treated with 11 different conditions; #1) Vehicle_NormEnv (with potential exposure for environmental PBDEs derived from plastics in cages), #2) Vehicle (no exposure to PBDEs and ovarian hormones), #3) 17β-estradiol (E2), #4) E2 and progesterone (P4), #5) E2 and ICI 182, 780 (ER antagonist; ICI), #6) low dose of PBDEs for 20 weeks (Low_PBDE), #7) Low_PBDE and E2, #8) Low_PBDE, E2, and P4, #9) high dose of PBDEs (20 times of Low_PBDE) for 1 week (High_PBDE), #10) High_PBDE and E2, #11) High_PBDE, E2, and P4. Ovarian hormones and ICI were administered for 1 week and once, respectively, at the final week of PBDEs treatment. A sample from age-matched intact mice were also included in the experimental groups. The 4th mammary glands were harvested at the end point and single-cell RNA sequencing was performed.

first: Shiuan

last: Chen

first: Kohei

last: Saeki

first: Ryohei

last: Yoshitake


title: Synthetic genomic reconstitution reveals principles of mammalian Hox cluster regulation [RNA-Seq]

status: Public on Dec 16 2021

city: Seattle

first: Sudarshan

last: Pinglay

state: WA

address: 3720 15th Ave NE

institute: University of Washington

summary: Precise Hox gene expression is crucial for embryonic patterning. Local transcription factor binding and distal enhancer elements have emerged as the major regulatory modes controlling the initiation and maintenance of Hox gene expression. However, quantifying their relative contributions has remained elusive. Here, we introduce ‘synthetic regulatory reconstitution’, a novel conceptual framework for studying gene regulation and apply it to the mammalian HoxA cluster. To measure the HoxA intrinsic regulatory potential and distal enhancer contributions, we de novo synthesized and delivered variant rat HoxA clusters (130-170 kilobases each) to an ectopic location in the mouse genome. We find that a minimal HoxA cluster lacking distal enhancers induces the appropriate gene set and establishes distinct chromatin domains in response to patterning signals, while distal enhancers are required for full transcriptional output. These results suggest that the genomically compact Hox clusters contain all the information to decode patterning signals and maintain positional information

overall_design: RNA-Seq was used to study global gene expression in cells carrying synthetic Hox cluster variants during ESC-to-MN differentiation

first: Milica

last: Bulajić

first: Dylan

middle: P

last: Rahe

first: Emily

last: Huang

first: Ran

last: Brosh

first: Sergei

last: German

last: Cadley

first: Lila

last: Rieber

first: Nicole

last: Easo

first: Shaun

last: Mahony

first: Matthew

last: Maurano

first: Liam

last: Holt

first: Esteban

last: Mazzoni

first: Jef

middle: D

last: Boeke


title: Synthetic genomic reconstitution reveals principles of mammalian Hox cluster regulation

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

sample_organism:
Mus musculus
Rattus norvegicus

platform_organism:
Mus musculus
Rattus norvegicus

overall_design: Refer to individual Series


title: Single-cell atlas of lineage states, tumor microenvironment and subtype specific expression programs in gastric cancer

status: Public on Oct 05 2021

city: Singapore

first: Kie Kyon

state: Select State/Province

address: 8 College Road

country: Singapore

institute: Duke-NUS Graduate Medical School

summary:
Gastric cancer (GC) heterogeneity between and within tumors represents a barrier to disease management. We generated a comprehensive single-cell atlas of GC comprising 31 primary gastric tumor samples representing clinical stages I-IV and histological subtypes. We identified 34 distinct cell-lineage states, related by developmental trajectories and previously unreported rare cell populations. Many lineage states exhibited a distinctive tumor-associated expression profile, each contributing individually to a combined tumor-wide molecular collage. We observed increased plasma cell proportions as a feature of diffuse-type tumors associated with epithelial-resident KLF2, and a stagewise accrual of novel cancer-associated fibroblast sub-populations marked by high INHBA and FAP co-expression. Our results provide a high-resolution molecular resource for GC translational studies, identifying intra- and inter-patient lineage-states across distinct GC subtypes.

#### GEO title mapping with the ID in PMID:34642171 ####

Manuscript_ID	Primary_Tumor	Primary_Normal	Peritoneal_Tumor	Peritoneal_Normal
NGCII521	sample7.csv	sample6.csv	-	-
NGCII513	sample22.csv	sample21.csv	-	-
NGCII512	sample26.csv	sample25.csv	-	-
NGCII520	sample5.csv	sample4.csv	-	-
NGCII514	sample24.csv	sample23.csv	-	-
NGCII518	sample2.csv	sample1.csv	-	-
NGCII525	sample10.csv	sample9.csv	-	-
NGCII527	sample12.csv	sample11.csv	-	-
NGCII538	sample36.csv	sample35.csv	sample38.csv	sample37.csv
NGCII539	sample32.csv	-	-	-
NGCII529	sample13.csv	-	-	-
NGCII511	sample15.csv	-	-	-
NGCII498	sample18.csv	-	-	-
NGCII522	sample29.csv	-	-	-
NGCII499	sample16.csv	-	-	-
NGCII502	sample14.csv	-	-	-
NGCII509	sample17.csv	-	-	-
NGCII540	sample33.csv	-	-	-
NGCII541	sample34.csv	-	-	-
NGCII543	sample39.csv	-	-	-
NGCII510	sample27.csv	-	-	-
NGCII519	sample3.csv	-	-	-
NGCII531	sample28.csv	-	-	-
NGCII545	sample40.csv	-	-	-
NGCII533	sample30.csv	-	-	-
NGCII524	sample8.csv	-	-	-
NGCII536	-	sample31.csv	-	-
NGCII011 	-	-	sample19.csv	-
NGCII015	-	-	sample20.csv	-

overall_design:
Profiling of 31 gastric malignancies at single-cell resolution
*** Raw files were not submitted due to patient privacy concerns ***

first: Vikrant

last: Kumar

first: Kalpana

last: Ramnarayanan

first: Patrick

last: Tan


title: RNA-Seq of circHIPK3 knockdown (KD) samples in UMUC3 and J82

status: Public on Oct 01 2021

city: Århus N

first: Trine Line

middle: Hauge

last: Okholm

address: Palle Juul-Jensens Boulevard 99

department: Department of Molecular Medicine (MOMA)

institute: Aarhus University Hospital

summary: We profile gene expression upon circHIPK3 KD in two bladder cancer cell lines UMUC3 and J82

overall_design: Cells were treated with a control scramble (scr) siRNA or an siRNA that specifically knock down the expression of circHIPK3. mRNA profiling upon treatment were generated using QuantSeq

first: Trine-Line

first: Andreas

middle: B

last: Kamstrup

first: Søren

last: Vang

first: Christian

middle: K

last: Damgaard

first: Jakob

last: Pedersen


title: Epigenetic alterations are associated with gastric emptying disturbances in Diabetes Mellitus

status: Public on Dec 26 2021

city: Rochester

first: Aditya

last: Bhagwate

state: MN

address: 200 1st Street SW

institute: Mayo Clinic

summary:
Introduction.  Epigenetic modifications have been implicated to mediate several complications of diabetes mellitus (DM), especially nephropathy and retinopathy. Our aims were to ascertain if epigenetic alterations in whole blood discriminate among DM patients with normal, delayed and rapid gastric emptying (GE).
Methods.  Using ChIP-seq (Chromatin immunoprecipitation combined with next generation sequencing) assays, we compared the genome-wide enrichment of three histone modifications (ie, H3K4me3, H3K9ac and H3K27ac) in buffy coats from 20 DM patients with normal (n=6), delayed (n=8), or rapid (n=6) GE.
Results.  Between DM patients with delayed versus normal GE, there were 108 and 54 genes that were differentially-bound (FDR < 0.05) with H3K27ac and H3K9ac; 100 genes were differentially bound with H3K9ac in patients with rapid versus normal GE.  The  differentially bound genes with  H3K27ac were functionally linked to the type 2 immune response, particularly Th2 cell activation and function (eg, CCR3, CRLF2, CXCR4, IL5RA, and IL1RL1) and glucose homeostasis (FBP-1,  PDE4A, CMKLR1).  For H3K9ac, the differentially occupied genes were related to T cell development and function (eg, ICOS and CCR3) and innate immunity (RELB, CD300LB, CLEC2D).  Compared to normal, rapid GE had differential H3K9ac peaks at the promoter site of diverse immunity-related genes (eg, TNFRSF25 and CXCR4) and genes related to insulin resistance and glucose metabolism.  The motif analysis disclosed enrichment of binding sites for several transcription factors relevant to the pathogenesis and complications of DM.
Conclusions. GE disturbances in DM are associated with epigenetic alterations that may serve as biomarkers and provide clues to the pathogenesis

overall_design: Comparison of 3 histone marks (H3K4me3, H3K9ac and H3K27ac) in buffy coat samples from DM patients with delayed versus normal GE and rapid versus normal GE.

first: Susrutha

last: Puthanmadhom Narayanan

first: Jeong-Heon

last: Lee

first: Adil

last: Bharucha


title: Characterization of heterogeneity in gastric cancer cells derived from independent lineages at single-cell resolution

status: Public on Jan 30 2022

city: GOYANG

first: JIHYUN

last: KIM

address: 323 ILSAN-RO

country: South Korea

institute: National cancer center

summary: Analysis of genomic and transcriptomic profiling has proposed new insights for diagnosis and prognosis in gastric cancer (GC). Human GCs are a unified model composed of diverse cells, including premalignant, immune and cancer. In this study, we present a human cell population of GC and premalignant states at single cell resolution using the 10X Chromium platform. We profiled 112,041 gastric cell landscape across 24 individuals with adjacent normal and GC lesions.

overall_design: For a total of 24 patients with 9 intestinal gastric cancers (IGC) and 15 diffuse gastric cancers (DGC), 13,022 cells consisted of 47 biopsies both 24 GC lesions and 23 adjacent normals were selected after a quality control.

first: Sooyoung

last: Cho


title: DNA methylation analysis of placenta samples exposed to maternal smoking during pregnancy

status: Public on Sep 20 2021

city: Beaverton

first: Lyndsey

middle: Elizabeth

last: Shorey-Kendrick

state: Oregon

address: 505 NW 185th Ave

institute: Oregon Health and Science University

summary: Epigenome-wide profiling of placental DNAm in samples obtained from 72 smokers enrolled in the VCSIP RCT: NCT03203603 (35 supplemented with placebo, 37 supplemented with vitamin C) and 24 never-smokers for reference.

overall_design: Illumina MethylationEPIC analysis performed on 96 human placentas collected at term.

first: Cindy

last: McEvoy

first: Robert

last: Tepper

first: Eliot

last: Spindel


title: Spatially distinct reprogramming of the tumor microenvironment based on tumor invasion in diffuse-type gastric cancers

status: Public on Aug 09 2021

city: Seoul

first: Hye Young

last: Jeong

address: Banpodaero 222

institute: Catholic University

summary: The invasive potential of gastric cancers (GCs) defines the hallmarks of malignancies; however, the cellular components and their molecular features associated with tumor invasiveness in GC microenvironments (TME) are poorly understood. In this study, we constructed a comprehensive atlas of 23,060 single cells obtained from surgically dissected superficial and deep layers of five diffuse-type GC along with matched normal. As a result, seven major cell types were identified. Fibroblasts, endothelial cells, and myeloid cells were categorized as being enriched in the deep layers. Cell type-specific clustering further revealed that the superficial-to-deep layer transition is associated with enrichment in inflammatory endothelial cells and fibroblasts with upregulated CCL2 transcripts. This study reveals the spatial reprogramming of the TME that may underlie invasive tumor potential in diffuse-type GC. This TME profiling across tumor layers suggests new targets, such as CCL2, that can modify the TME to inhibit tumor progression in diffuse-type GC.

overall_design: A scRNAseq analysis of 30,365 cells from diffuse-type gastric cancer using 10X Genomics.

first: Hoon

last: Hur

first: Tae

last: Kim


title: Distinct stage-specific transcriptional states of B cells in human tonsillar tissue [single-cell RNA-seq]

status: Public on Aug 16 2021

city: Philadelphia

first: Diego

middle: A

last: Espinoza

address: 3400 Civic Center Boulevard

institute: University of Pennsylvania

summary: Defining B cell states in human tonsillar tissue using single cell transcriptomics.

overall_design: Methods: 10X Genomics 3' scRNA-seq of human tonsillar B cells from 3 donors. One donor was run across three wells of the 10X reaction. Cells were FACS-sorted (CD3-/CD14-/CD19+) and rested overnight prior to scRNA-seq. We used CellRanger v 3.0.1 to quantify our single cell transcriptomes.

first: Rui

last: Li


title: Baseline transcriptomic data of the CiGEnC Delta HLA cell line

status: Public on Aug 05 2021

city: PARIS

first: Benjamin

last: SAINTPIERRE

address: 22 rue méchain

country: France

institute: Inserm

summary: We modified the CiGEnC cell line by CRISPR Cas9 genome edition to suppress both classI and classII HLA molecules production by CIITA and B2M knock out. After 7 days of differentiation at 37°C, we extracted RNA from the cell line and performed bulk RNA sequencing to provide a basal profile of the whole transcriptom of the cell line

overall_design: Purpose: To provide baseline transcriptomic data of the CiGEnC Delta HLA cell line for the scientific community

first: Baptiste

last: Lamarthée

first: Dany

last: Anglicheau

first: Emilie

last: Lebraud


title: Non-Canonical Epigenetic Regulation of HIV Infection in Macrophage

status: Public on Aug 12 2021

first: Priyankara

middle: J

last: Wickramasinghe

address: 3601 Spruce Street

department: Bioinformatics

institute: The Wistar Institute

summary: Persistently infected macrophages serve as a long-term HIV reservoir and barrier to viral eradication, and also contribute to neurological complications in patients despite antiretroviral therapy (ART). To better understand the regulation of HIV in macrophages, we compared HIV infected human monocyte derived macrophages (MDM) to acutely infected primary CD4 T cells and Jurkat cell lines latently infected with HIV (JLAT). HIV genomes in MDM were actively transcribed despite enrichment with heterochromatin-associated H3K9me3 across the complete HIV genome in combination with elevated activation marks of H3K9ac and H3K27ac at the LTR. In contrast, JLAT showed conventional bivalent H3K4me3/H3K27me3 while CD4 showed an intermediate epigenotype. 5‘-methylcytosine (5mC) was enriched across the HIV genome in latently infected JLAT cells, while 5‘-hydroxymethylcytosine (5hmc) was enriched in CD4 and MDM. HIV infection induced multinucleation of MDMs along with DNA damage associate p53 phosphorylation, as well as loss of TET2 and the nuclear redistribution of 5-hydoxymethylation. RNA-seq analysis demonstrated that MDMs have a distinct transcriptional response to HIV persistent infection, including activation of CCL7, LAG3, and interferon signaling. Taken together, our findings suggest that HIV induces a unique macrophage nuclear and transcriptional profile, and viral genomes are maintained in a non-canonical bivalent epigenetic state.

overall_design: RNA-seq of HIV-infected MDM and CD4 cells.

first: Paul

last: Lieberman

first: Fang

last: Lu


title: Expression data from human A549 cells and exosomes under room air (RA) or intermittent hypoxia (IH)

status: Public on Jul 29 2021

city: Zhengzhou

first: Jie

last: Ren

address: No.1 Jianshe East Road, Erqi District

institute: The Fifst Affilated Hospital of Zhengzhou University

summary:
Studies have shown that IH may promote the development of non-small-cell lung cancer (NSCLC),  Exosomes carry specific proteins, lipids,  small molecule RNAs (miRNAs)  as well as other bioactive substances, which play an important role in tumor growth.
The role of exosomal miRNAs in the promotion of tumor development by IH has not been studied.

overall_design: We used microarray technology to compare miRNA differentially expressed in IH exosomes and RA exosomes, and IH A549 cells and RA A549 cells

first: Hui-guo

last: Liu


title: DIS3 mediated RNA decay is required for maintenance of spermatogenic lineage in mice

status: Public on Jul 15 2021

city: Bethesda

first: Zhengpin

last: Wang

state: MD

address: National Institutes of Health, 9000 Rockville Pike

department: Laboratory of Cellular and Developmental Biology

institute: NIDDK, NIH

summary: Spermatogonial stem cells (SSCs) self-renewal and differentiation are the foundation for continious spermatognenesis in mice. Here, we investigate the essential role of DIS3 in maintaining SSC homeostasis and facilitating germ cell differentiation to ensure male fertility. Conditional inactivation of DIS3 in male germ cells have severely impaired SSC self-renewal and differentiation, which results in the failure of spermatogenesis associated with a Sertoli cell-only syndrome and adult sterility. RNA-seq analysis reveals that Dis3 deficiency abolishes its nucleolytic activity and causes significant dysregulation of the expression of transcripts in Dis3 mutant testes. We have also found that the pervasive transcription products described previously, such as Promoter Upstream Transcripts (PROMPTs), accumulate robustly upon DIS3 dysfunction in Dis3 cKO testes. In addition, scRNA-seq analysis indicates that DIS3 mutation significantly impairs germline stem cell development that blocks stem cell proliferation and differentiation. Overall, we show that DIS3 ribonuclease plays a critical role in the maintenance of spermatogenic lineage during spermatogenesis in mice.

overall_design: scRNA-seq was performed using P6 testicular cells from control and DIS3 knockout mice to identify different subpopulations. Re-clustering of germ cells was performed to determine the germ cell distribution and differentially expressed genes in knockout mice.

first: Xiaojiang

last: Xu

first: Jurrien

last: Dean


title: Reduced TCRγδ signal strength engages phosphatidylinositol 3-kinase (PI3K) to drive thymic development of IL-17A-secreting  γδ T cells

status: Public on Jul 05 2021

city: London

first: Daniel

last: Pennington

address: 4 Newark Street

institute: Blizard Institute

summary: Reduced TCRγδ signal strength manifest by constrained Syk activity engages PI3K to maintain expression of key master regulators of the IL-17 program; RORγt and c-Maf, and drive thymic development of IL-17A-secreting γδ T cells (γδ17 cells). Notably, inhibition of PI3K not only abrogates γδ17 cell development, but also permits γδ progenitors to adopt a type-I interferon gene expression signature that identifies a novel CD8(+)Sca-1(+) γδ T cell subset.

overall_design: Total γδ T cells were sorted from foetal C57BL/6 thymic lobes cultured for 8 days in the presence of a pan-PI3K inhibitor (ZSTK474) or under control conditions.

first: Nital

last: Sumaria


title: Single-cell RNA-sequencing of mouse islets exposed to proinflammatory cytokines

status: Public on Apr 15 2021

city: Chicago

first: Weiguo

last: Cui

summary: Exposure to proinflammatory cytokines is believed to contribute to pancreatic β-cells during diabetes development.  While some cytokine-mediated changes in islet gene expression are known, the heterogeneity of the response is not well-understood. Following 6 hour treatment with interleukin-1 beta (IL-1β) and interferon-gamma (IFN-γ) alone or together, mouse islets were subjected to single-cell RNA-sequencing (scRNA-seq). Inducible nitric oxide synthase (iNOS) mRNA (Nos2), antiviral genes, and immune-associated genes were induced in a subset of β-cells in response to both cytokines, while IL-1β alone activated only antiviral genes. Subsets of α- and δ-cells expressed Nos2 and exhibited similar gene expression changes as β-cells, including induction of antiviral genes and repression of identity genes. Finally, cytokine-responsiveness was inversely correlated with expression of genes encoding heat shock proteins. Our findings show that all endocrine cell types respond to cytokines, IL-1β induces the expression of protective genes in β-cells, and cellular stress gene expression is associated with an inhibition in cytokine signaling.

overall_design: Four samples of murine islets (no cytokine treatment, IL-1B only, IFNg only, IL-1B and IFNg exposure for 6 hours) were prepared using 10x Genomics Chromium platform

first: John

last: Corbett

first: Jennifer

last: Stancill


title: DNA methylation profiles for Standardized control samples

status: Public on May 14 2021

city: Research Triangle Park

first: Zongli

last: xu

state: NC

address: 111 TW Alexander Dr

department: Epidemiology Branch

institute: NIEHS

summary: Genome-wide DNA methylation profiling of Standardized control samples were use to evaluate whether measurement reliability can be improved at probe level by various preprocessing pipelines

overall_design: Unmethylated DNA from the HCT116 double knock out (DKO) cell line and fully methylated DNA is from this same HCT116 DKO that is enzymatically methylated were mixed in different proportion to create standardized control samples with specific methylation levels: 0 5 10 20 40 50 60 80 and 100% methylated.

first: Jack

last: Taylor


title: CPD-seq mapping of UV damage repair in elf1 mutant yeast

status: Public on Apr 05 2021

city: Pullman

middle: J.

last: Wyrick

address: Biotechnology Life Sciences 241

department: School of Molecular Biosciences

institute: Washington State University

summary: Elf1 is an important transcription elongation factor that has been implicated in transcription coupled-nucleotide excision repair (TC-NER). Here, we have used a high-throughput sequencing method known as CPD-seq to map the repair of UV-induced cyclobutane pyrimidine dimers (CPDs) at single nucleotide resolution across the yeast genome in elf1 mutant cells. Analysis of CPD repair indicates that Elf1 is important for CPD repair in the transcribed strand (TS) of yeast genes, indicating it plays an important role in TC-NER.

overall_design: UV repair data was analyzed for wild-type (WT) and mutant yeast cells deleted for the ELF1 gene. (i.e., elf1∆). Yeast cells were irradiated with 125J/m2 and allowed to repair for 0 or 2 hours.

first: Kathiresan

last: Selvam


title: Tenomodulin prevents trauma-induced heterotopic ossification in tendon

status: Public on Nov 08 2021

city: Regensburg

first: Xin

address: Universitätsstraße 31

institute: University of Regensburg

summary: We have reported that loss of Tnmd leads to inferior early tendon repair characterized by fibrovascular scaring and therefore hypothesized that its lack will persistently cause deficient repair during later stages. Tnmd knockout (Tnmd-/-) and wild-type (WT) animals were subjected to complete Achilles tendon surgical transection followed by end-to-end suture. Lineage tracing revealed a reduction in tendon-lineage cells marked by ScleraxisGFP, but an increase in alpha smooth muscle actin myofibroblasts in Tnmd-/- tendon scars. At the proliferative stage, more pro-inflammatory M1 macrophages and larger collagen II cartilaginous template were detected in this group. At the remodeling stage, histological scoring revealed lower repair quality in the injured Tnmd-/- tendons, which was coupled with higher HO quantified by micro-CT. Tendon biomechanical properties were compromised in both groups upon injury, however we identified an abnormal stiffening of non-injured Tnmd-/- tendons, which possessed higher static and dynamic E-moduli. Pathologically thicker and abnormally shaped collagen fibrils were observed by TEM in Tnmd-/- tendons and this together with augmented HO resulted in diminished running capacity of Tnmd-/- mice. These novel findings demonstrate that Tnmd plays a protecting role against trauma-induced endochondral HO and can inspire the generation of novel therapeutics to accelerate repair.

overall_design: Tenogenic-primed Scleraxis-expressing cells were isolated from the Achilles tendon from uninjured transgenic Tnmd-/- ScxGFP+ and Tnmd WT ScxGFP+ mice. Six cells/genotype were used for analysis.

first: Denitsa

last: Docheva

first: Manuel

last: Delgado Caceres

first: Adithi

middle: R

last: Varadarajan

first: Jens

last: Warfsmann


title: DNA methylation profiles for Sister Study duplicate samples

summary: Genome-wide DNA methylation profiling of blood duplicate samples (n=128) From Sister Study were used to evaluate how concordance between duplicates were improved at sample level by various methylation preprocessing pipelines

overall_design: Bisulphite-converted DNA from the 256 samples (128 duplicate pairs) were hybridized to the Illumina Infinium 450k Human Methylation Beadchip v1. These DNA samples were randomly distributed along with other ~3000 blood sample on plates and arrays. The two duplicates of a sample were always bisulfite-converted on different plates and assayed on different arrays


title: Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features

status: Public on Mar 17 2021

city: Houston

first: Jiexin

last: Zhang

state: TX

address: 1515 Holcombe Blvd

department: Bioinformatics & Computational Biology

institute: UT MD Anderson Cancer Center

summary:
To assess the dynamic changes in the immune contexture during early lung carcinogenesis, we performed
immune profiling using the nCounter PanCancer Immune Profiling Panel on resected lung ADCs and their precursors .

overall_design: n=9 for AAH (atypical adenomatous hyperplasia), n=11 for AIS (adenocarcinoma in situ), n=21 for MIA (minimally invasive adenocarcinoma), and n=6 for invasive ADC (adenocarcinoma)

first: Jianjun


title: Enhancer-promoter interactions and transcription are maintained upon acute loss of CTCF, cohesin, WAPL, and YY1

city: Berkeley

first: Xavier

last: Darzacq

address: 475D Li Ka Shing Center

department: Molecular and Cell Biology

institute: University of California, Berkeley

summary: We use high-resolution Micro-C, ChIP-seq and nascent and total transcript profiling to show that Enhancer-Promoter (E-P) interactions are largely insensitive to acute depletion of CTCF, cohesin, WAPL and YY1.

overall_design: We performed ChIP-seq, RNA-seq, mNET-seq, and Micro-C in mESCs with either CTCF (clone C58), the cohesin subunit RAD21 (clone F1), the cohesin unloader WAPL (clone C40) or YY1 transcription factor (clone YD39) endogenously tagged with an auxin-inducible degron, 3 hours after treatment with either ethanol alone (UT) or ethanol-dissolved auxin (IAA, 500 mM). For ChIP-seq, we performed two biological replicates per each sample and condition, immunoprecipitating chromatin with antibodies against CTCF, the cohesin subunits RAD21, SMC1A and SMC3, and YY1 (4 cell types, 2 conditions, 5 antibodies + input in duplicate, for a total of 96 libraries). For RNA-seq, mNET-seq, and Micro-C, we also performed two biological replicates for each sample and condition.

first: Tsung-Han

last: Hsieh

first: Claudia

last: Cattoglio

first: Elena

last: Slobodyanyuk

first: Robert

last: Tjian


title: Role of CCR2+ Myeloid Cells in Inflammatory Responses Driven by Mutation in Surfactant Protein-C Expression

status: Public on Feb 07 2021

city: Salt Lake City

first: Alessandro

last: Venosa

institute: University of Utah

summary: Acute inflammatory exacerbations (AIE) represent precipitous deteriorations of a number of chronic lung conditions, including pulmonary fibrosis (PF), chronic obstructive pulmonary disease and asthma. AIEs are marked by diffuse and persistent polycellular alveolitis that profoundly accelerate lung function decline and mortality. In particular, excess monocyte mobilization during AIE and their persistence in the lung have been suggested to be linked to poor disease outcome. We have developed a mutant model of pulmonary fibrosis leveraging the PF-linked missense isoleucine to threonine substitution at position 73 [I73T] in the alveolar type-2 cell-restricted Surfactant Protein-C [SP-C] gene [SFTPC]. With this toolbox at hand, the present work investigates the dynamics of resident alveolar macrophages and peripheral monocytes during the initiation and progression of AIE-PF.   FACS analysis of SigF+CD11b- alveolar macrophages and Ly6Chi monocytes isolated 3 d and 14 d after SP-CI73T injury and performed RNA sequencing. Pathway and gene expression analysis revelaed dynamic transcriptional changes associated with “Innate Immunity’ and ‘Extracellular Matrix Organization’ signaling. Supported by previous pharmacological evidence, genetic ablation of CCR2+ monocytes (SP-CI73TCCR2KO) resulted in improved lung histology, mouse survival, and reduced inflammation compared to SP-CI73TCCR2WT cohorts.  Immunohistochemical and in situ hybridization analysis revealed comparable levels of tgfb1 mRNA expression localized primarily parenchymal cells found nearby foci of injury. Our results also confirmed reduced inflammatory activation (iNOS, Arg1) in SP-CI73TCCR2KO lungs as well as partial colocalization of tgfb1 mRNA expression in Arg1+ cells. These results provide a detailed picture on the role of resident macrophages and recruited monocytes in the context of AIE-PF driven by alveolar epithelial dysfunction.

overall_design: Examination of cell sorted lung alveolar macrophages and monocytes isolated during initiation (3 d) and peak (14 d) lung injury

first: Sophie

last: Cowman


title: Whole blood transcriptional signatures associated with rapid antidepressant response to ketamine in patients with treatment resistant depression.

status: Public on Oct 13 2021

city: New York

first: Aarthi

last: Ramakrishnan

address: 1425 Madison Avenue

department: Neuroscience

institute: Icahn School of Medicine at Mount Sinai

summary: Ketamine has rapid and sustained antidepressant effects in patients with treatment resistant depression (TRD). However, the underlying mechanisms of action are not well understood. There is increasing evidence that TRD is associated with a pro-inflammatory state and that ketamine may inhibit inflammatory cytokine production. We investigated whole blood transcriptional profiles related to TRD and gene expression changes associated with treatment response to ketamine. Whole blood was collected at baseline (21 healthy controls [HC], 26 patients with TRD) and then again in patients with TRD 24 hours following a single intravenous infusion of ketamine (0.5 mg/kg). We performed RNA-sequencing and compared a) baseline transcriptional profiles between patients with TRD and HC, b) responders vs. non-responders before ketamine treatment, and c) gene expression signatures associated with clinical improvement. At baseline, patients with TRD compared to HC were characterized by a gene expression signature indicative of interferon signaling pathway activation. Prior to ketamine administration, the metabotropic glutamate receptor gene GRM2 and the ionotropic glutamate receptor gene GRIN2D were upregulated in responders compared to non-responders. Ketamine response was associated with the downregulation of multiple genes coding for pro-inflammatory cytokines, the predicted inhibition of several interferon signaling associated upstream regulators and the downregulation of Indoleamine 2,3-Dioxygenase 1 (IDO1). The current study indicates that response to ketamine may be associated with up-regulation of glutamate receptors at baseline, and linked to transcriptional changes indicative of an anti-inflammatory response following ketamine. One specific anti-inflammatory mechanism might be the downregulation of IDO1 via inhibition of the interferon pathway.

overall_design: RNA-sequencing was done on human MDD and control subjects to compare a) baseline transcriptional profiles between patients with Treatment Resistant Depression (TRD) and Human Controls (HC), b) responders vs. non-responders before ketamine treatment, and c) gene expression signatures associated with clinical improvement.

first: Flurin

last: Cathomas

first: Laura

last: Bevilacqua

first: Scott

last: Russo

first: James

last: Murrough


title: Balancing cohesin eviction and retention prevents aberrant chromosomal interactions, Polycomb-mediated repression, and X-inactivation

status: Public on Mar 15 2021

city: Boston

first: Andrea

middle: June

last: Kriz

state: MA

address: 185 Cambridge St

department: Molecular Biology

institute: Massachusetts General Hospital, Harvard Medical School

summary: Depletion of architectural factors globally alters chromatin structure, but only modestly affects gene expression. We revisit the structure-function relationship using the inactive X chromosome (Xi) as a model. We investigate cohesin imbalances by forcing its depletion or retention using degron-tagged RAD21 (cohesin subunit) or WAPL (cohesin release factor). Interestingly, cohesin loss disrupts Xi superstructure, unveiling superloops between escapee genes, with minimal effect on gene repression. By contrast, forced cohesin retention markedly affects Xi superstructure and compromises spreading of Xist RNA-Polycomb complexes, attenuating Xi silencing. Effects are greatest at distal chromosomal ends, where looping contacts with the Xist locus are weakened. Surprisingly, cohesin loss created an ?Xi superloop? and cohesin retention created ?Xi megadomains? on the active X. Across the genome, a proper cohesin balance protects against aberrant inter-chromosomal interactions and tempers Polycomb-mediated repression. We conclude that a balance of cohesin eviction and retention regulates X-inactivation and inter-chromosomal interactions across the genome.

overall_design: RAD21 ChIP-seq, RAD21 and H3K27me3 calibrated ChIP-seq, RNA-seq, PRO-seq, Hi-C, Xist CHART-seq

first: A

first: D

last: Colognori

first: H

last: Sunwoo

first: B

last: Nabet

first: J

middle: T

last: Lee


title: Single-cell RNA sequencing reveals transcriptome alterations of liver sinusoidal endothelial cells in different zonal microenvironments of cirrhotic livers

status: Public on Feb 05 2021

city: New Haven

first: Yasuko

last: Iwakiri

state: CT

address: 300 Cedar street

department: Section of Digestive Diseases

institute: Yale University School of Medicine

summary: Dysfunction of liver endothelial cells (ECs), especially sinusoid endothelial cells (LSECs), play a key role in progression of liver fibrosis/cirrhosis.  Here, we reported a map which reveals heterogeneity and spatial distribution of liver ECs in normal versus cirrhotic mouse liver and determined liver zonal specific transcriptomic changes of LSECs associated with liver cirrhosis using single-cell RNA sequencing technology. We identified 6 clusters of liver EC populations including 3 clusters of LSECs, 2 clusters of vascular ECs (arterial and central venous ECs) and 1 cluster of lymphatic ECs. Particularly, we mapped the 3 clusters of LSECs in Zone1-3. We found that liver EC identities are conserved even in liver cirrhosis and that Zone3 LSECs are most susceptible to damages associated with liver cirrhosis with increased capillarization and decreased abilities to regulate endocytosis and vascular tone. Altogether, this study deepens our knowledge for the pathophysiology of cirrhosis at a spatial and cell-specific level, which are indispensable for the development of novel therapeutic strategies to target liver ECs.

overall_design: We performed 10x scRNA sequencing analysis on liver EC enriched populations isolated from control and cirrhotic mice.  All mice used were EC-specific enhanced green fluorescent protein (eGFP) expressing mice (Cdh5-Cre+, mTmG mice).GFP-positive and non-apoptotic liver ECs were selected from non-parenchymal cell fractions pooled from 3 mice per group by FACS.

first: Tingting

last: Su


title: Identification of a targetable KRAS-mutant epithelial population in non-small cell lung cancer

status: Public on Sep 16 2021

first: Mahmoud

middle: Adel

last: Bassal

state: Massachusetts

address: 3 Blackfan Circle

department: Hematology and Oncology

institute: Beth Israel Deaconess Medical Center

summary:
Lung cancer is the leading cause of cancer deaths. Tumor heterogeneity, which hampers development of targeted therapies, was herein deconvoluted via single cell RNA sequencing in aggressive human adenocarcinomas (carrying Kras-mutations) and comparable murine model. We identified a tumor-specific, mutant-KRAS-associated subpopulation which is conserved in both human and murine lung cancer. We previously reported a key role for the oncogene BMI-1 in adenocarcinomas. We therefore investigated the effects of in vivo
PTC596 treatment, which affects BMI-1 activity, in our murine model. Post-treatment, MRI analysis showed decreased tumor size, while single cell transcriptomics concomitantly detected near complete ablation of the mutant-KRAS-associated subpopulation, signifying the presence of a pharmacologically targetable, tumor-associated subpopulation. Our findings therefore hold promise for the development of a targeted therapy for KRAS-mutant adenocarcinomas.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design:
Single cell RNA sequencing (scRNAseq) of RBC-depleted cells from non-small cell lung tumor of 12 patients. ScRNAseq of lung tumors from KP model mice - 2 healthy samples, 2 tumor samples, 2 tumor PTC596 treated samples.
*** The submitter states "Human raw data are not available for this Series due to patient privacy concerns." " [We] will not be submitting the raw human data to dbGap or EGA in this case."
Thus, this submission is incomplete.

first: Giorgia

last: Maroni

first: Indira

last: Krishnan

first: Fhu

middle: C

last: Wai

first: Virginia

last: Savova

first: Rapolas

last: Zilionis

first: Valerie

last: Maymi

first: Nicole

last: Pandell

first: Eva

last: Csizmadia

first: Junyan

last: Zhang

first: Barbara

last: Storti

first: Julio

last: Castaño

first: Riccardo

last: Panella

first: Corinne

last: Gustafson

first: Sam

last: Fox

first: Rachel

last: Levy

first: Claire

middle: V

last: Meyerovitz

first: Peter

last: Tramontozzi

first: Kimberly

last: Vermilya

first: Assunta

last: De Rienzo

first: Stefania

last: Crucitta

first: Daniela

last: Basseres

first: Marla

last: Weetall

first: Art

last: Branstrom

first: Alessandra

last: Giorgetti

first: Marzia

last: Del Re

first: Romano

last: Danesi

first: Ranieri

last: Bizzarri

first: Henry

last: Yang

first: Olivier

last: Kocher

first: Maria

last: Magli

last: Welner

first: Allon

middle: M

last: Klein

first: Raphael

last: Bueno

first: Azhar

last: Ali

first: Daniel

middle: G

last: Tenen

first: Elena

last: Levantini


title: Lipid Droplet-Associated Hydrolase Mobilizes Oxysterol Stores and Inhibits Atheroma Growth and Progression

status: Public on Nov 10 2020

city: Urbana

first: Sushant

last: Bangru

state: Illinois

address: 600 S Mathews Avenue

department: Biochemistry

institute: University of Illinois, Urbana-Champaign

summary: Lipid droplets (LDs) of foam cells within atheroma contain abundant cholesterol, but also serve as reservoirs of central bioactive lipids. The mechanisms of storage and mobilization of many of these lipids remain obscure. LD-associated hydrolase (LDAH) localizes to LDs, has a lipase structure, and is abundant in atheroma. However, its lipid substrates and role in atherogenesis are unknown. Using knockout and transgenic mice we found that LDAH protects against atherosclerosis. Myeloid LDAH expression is sufficient to inhibit lesion progression and promote stable architectures, less necrotic, and richer in fibrillar collagen. Lipidomics coupled with RNA sequencing revealed that LDAH facilitates mobilization of esters of oxysterols that are liver X receptor agonists, leading to induction of cholesterol efflux transporters, reduced foam cell inflammation, and pro-fibrotic gene signatures. These studies identify LDAH as a novel player in neutral hydrolysis of esterified regulatory sterols that promotes atheroprotective and pro-stabilizing mechanisms beyond mass cholesterol removal.

overall_design: To identify LDAH regulated differentially expressed genes in peritoneal macrophages loaded with oxidized LDL, RNAseq was performed in these cells for both LDAH KO and LDAH trangenic  animals.

first: Young-Hwa

last: Goo

first: Auinash

last: Kalsotra

first: Antoni

last: Paul


title: Transcriptomic analysis of Kidney Machine normothermic perfusion and comparision to cold storage

status: Public on Oct 17 2020

city: Cambridge

first: John

middle: Robert

last: Ferdinand

address: Department of Medicine

institute: University of Cambridge

summary: Kidneys which had been taken for transplant but later declined were perfused for up to 4 hours using a normothermic perfusion (MNP) rig or left on ice (CS) and samples were taken for RNASeq at different time points. The effect of the addition of a heamoadsorber (HA) to the perfusion rig was also assessed.

overall_design: Study used a pair of kidneys from the same donor. One kidney was either left on ice and the other underwent machine perfusion or one underwent the standered perfusion method and the other had a heamoadsorber added to the rig to remove small molecules including cytokines.

first: J

first: S

last: Hosgood

first: M

middle: L

last: Nicklson

last: Clatworthy


title: Differential regulation of gonadotropins as revealed by transcriptomes of distinct LH and FSH cells of fish pituitary

status: Public on Oct 14 2020

city: rehovot

first: Berta

last: Levavi-Sivan

state: Israel

address: Hertzel

department: Animal sciences

institute: The Hebrew University of Jerusalem

summary: From mammals to fish, gametogenesis and sexual maturation are driven by luteinizing hormone (LH) and follicle-stimulating hormone (FSH), the gonadotropic hormones temporally secreted from the pituitary. Teleost fish are an excellent model for addressing the unique regulation and function of each gonadotropin cell because, unlike mammals, they synthesize and secrete LH and FSH from distinct cells. Only two very distant vertebrate classes (fish and birds), demonstrate the mono-hormonal strategy suggesting a potential convergent evolution. By performing cell specific transcriptome analysis of double-labelled transgenic Nile tilapia (Oreochromis niloticus) expressing GFP and RFP in LH or FSH cells, respectively, we identified genes specifically enriched in each cell type, revealing differences in hormone regulation, receptors expression, cell signaling, and electrical properties. We found that each LH and FSH cell in fish express unique GPCR signature that reveals the direct regulation of metabolic and homeostatic hormones. Comparing these novel transcriptomes to that of rat gonadotrophs revealed conserved genes that might specifically contribute to each gonadotropin activity in mammals, suggesting conserved mechanisms controlling the differential regulation of gonadotropins in vertebrates.

overall_design: RNA-seq of gonadotropic cells from pituitaries of mature females and males tilapia. LH cells, FSH cells, and Negative cells were isolated using FACS from a pool of 20 pituitaries, from each gender. The procedure was repeated 4 times, in total 24 samples were obtained.

first: Lian

last: Hollander-Cohen

first: Matan

last: Golan

last: Levavi-Siven


title: Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through "reverse phenotyping"

status: Public on May 25 2021

city: Biberach

first: Meshal

last: Ansari

address: Birkendorfer Straße 65

institute: Boehringer Ingelheim

summary: The in vivo phenotypic profile of T cells reactive to severe acute respiratory syndrome (SARS)-CoV-2 antigens remains poorly understood. Conventional methods to detect antigen-reactive T cells require in vitro antigenic re-stimulation or highly individualized peptide-human leukocyte antigen (pHLA) multimers. Here, we used single-cell RNA sequencing to identify and profile SARS-CoV-2-reactive T cells from Coronavirus Disease 2019 (COVID-19) patients. To do so, we induce transcriptional shifts by antigenic stimulation in vitro and take advantage of natural T cell receptor (TCR) sequences of clonally expanded T cells as barcodes for 'reverse phenotyping'. This allows identification of SARS-CoV-2-reactive TCRs and reveals phenotypic effects introduced by antigen-specific stimulation. We characterize transcriptional signatures of currently and previously activated SARS-CoV-2-reactive T cells, and show correspondence with phenotypes of T cells from the respiratory tract of patients with severe disease in the presence or absence of virus in independent cohorts. Reverse phenotyping is a powerful tool to provide an integrated insight into cellular states of SARS-CoV-2-reactive T cells across tissues and activation states.

overall_design:
Single-cell transcriptomics experiment on Tracheal Apspirates and blood samples of severely diseased COVID-19 Patients
*** Raw data not available due to patient privacy concerns ***

first: Fischer

middle: S

last: David

first: Karolin

middle: I

last: Wagner

first: Benjamin

last: Schubert

first: Fabian

last: Theis

first: Herbert

last: Schiller

first: Dirk

middle: H

last: Busch

first: Kilian

last: Schober


title: Distinct roles for ATP-dependent chromatin remodeling enzymes in nucleotide excision repair in yeast

status: Public on Apr 12 2021

last: Wyrick

summary: Nucleosomes are a significant barrier to the repair of UV damage because they impede damage recognition by nucleotide excision repair (NER). The RSC and SWI/SNF chromatin remodelers function in cells to promote DNA access by moving or evicting nucleosomes and both have been linked to NER in yeast. Here, we report genome-wide repair maps of UV-induced cyclobutane pyrimidine dimers (CPDs) in yeast cells lacking RSC or SWI/SNF activity. Our data indicate that SWI/SNF is not generally required for NER, but instead promotes repair of CPD lesions at specific yeast genes. In contrast, mutation or depletion of RSC subunits causes a general defect in NER across the yeast genome. Our data indicate that RSC is required for repair not only in nucleosomal DNA, but also neighboring linker DNA and nucleosome-free regions (NFRs). Furthermore, our data indicate that RSC plays a direct role in transcription coupled-NER (TC-NER) of transcribed DNA. These findings help to define the specific genomic and chromatin contexts in which each chromatin remodeler functions in DNA repair, and indicate that RSC plays a unique function in facilitating repair by both NER subpathways.

overall_design: UV-induced CPD lesions were mapped in yeast cells both Immediately after UV damage formation (0hr time point) and following two hours of repair (2hr time point) using the CPD-seq method. Repair of CPD lesions was measured in both wild-type (WT) yeast and yeast cells mutated or depleted for subunits of the SWI/SNF or RSC ATP-dependent chromatin remodeling complexes.

first: Kaitlynne

last: Bohm


title: The loss of RNA N 6-adenosine methyltransferase Mettl14 in tumor-associated macrophages promotes CD8 + T cell dysfunction and tumor growth

status: Public on Apr 10 2021

first: Chuanyuan

last: Chen

address: 9000 Rockville Pike, Building 37

department: National Cancer Institute

institute: National Institutes of Health

summary: Tumor-associated macrophages (TAMs) can dampen the antitumor activity of T cells, yet the underlying mechanism remains incompletely understood. Here, we show that C1q+ TAMs are regulated by an RNA N6-methyladenosine (m6A) program and modulate tumor-infiltrating CD8+ T cells by expressing multiple immunomodulatory ligands. Macrophage-specific knockout of an m6A methyltransferase Mettl14 drives CD8+ T cell differentiation along a dysfunctional trajectory, impairing CD8+ T cells to eliminate tumors. Mettl14-deficient C1q+ TAMs show a decreased m6A abundance on and a higher level of transcripts of Ebi3, a cytokine subunit. In addition, neutralization of EBI3 leads to reinvigoration of dysfunctional CD8+ T cells and overcomes immunosuppressive impact in mice. We show that the METTL14-m6A levels are negatively correlated with dysfunctional T cell levels in patients with colorectal cancer, supporting the clinical relevance of this regulatory pathway. Thus, our study demonstrates how an m6A methyltransferase in TAMs promotes CD8+ T cell dysfunction and tumor progression.

overall_design: Tumor infiltrating macrophages from WT and Mettl14 cKO mice in LLC model were used to generate bulk RNAseq and m6Aseq libraries. Tumor infiltrating immune cells from LLC model and B16 model were used to generate single cell RNAseq libraries. Tumor infiltrating macrophages from WT and Mettl14 cKO mice in B16 model were used to generate bulk RNAseq libraries. Tumor infiltrating stromal cells  from colon cancer patients  were used to generate bulk RNAseq.

first: Dali

last: Han

first: Meng

last: Xu

first: Jun

last: Liu


title: Microarray gene expression data in control and DGCR8-depleting human mesenchymal stem cell

status: Public on Sep 01 2020

city: Daejeon

first: Yi-deun

last: Jung

address: 125 Gahac-ro, Yusung-Gu

institute: Korea Research Institute of Bioscience and Biotechnology

summary: To determine the miRNAs potentially responsible for the premature-senescence mediated gene expression regulation in human adipose-derived mesenchymal stem cells, we performed illumine bead microarray analyses on parental hMSCs, and globally depleted miRNAs by inhibiting DGCR8, an essential component of miRNA biogenesis. DGCR8 knockdown in hMSCs resulted in severe proliferation defects with senescence-associated changes including markedly increased reactive oxygen species (ROS) levels. In gene expression profiling, thousand two hundred and forty seven transcripts were upregulated and 1,136 genes were downregulated in Dgcr8 knockdown cells compared to control cells (p < 0.05, Fisher’s exact test).

overall_design:
Adipose-derived human mesenchymal stem cells were incubated at 37°C in 5% CO2 and grown to 50-60 % confluence, transfected with siRNAs against DGCR8 (siDGCR8) and GFP control (siGFP;ST Pharm) at a concentration of 32 nM using Lipofectamine 2000 (Invitrogen).

Replicative senescence mediated gene expression regulation in early (PDL; 3~5) and late passage (PDL; 15~40) human dipose-derived mesenchymal stem cells

first: Nayoung

last: Suh

first: Seul-Ki

last: Park