title: ChIP-seq for Histone variants and Histone modifictaions in WT and ddm1(-/-)  in 1st generation Leaves.

status: Public on May 09 2023

city: Vienna

first: Bhagyshree

middle: Babasaheb

last: Jamge

address: Dr. Bohr Gasse -3

country: Austria

institute: Gregor Mendel Institute

summary:
How histone intrinsic sequence variation or regulatory modifications regulate nucleosome interactions with transcription remain unclear. To clarify this question, we examined how histone variants and histone modifications assemble in the Arabidopsis thaliana genome, identifying a limited number of chromatin states that divide euchromatin and heterochromatin in biologically significant subdomains. We showed that histone variants were as significant as histone modifications to determine the composition of chromatin states. The loss of function of the chromatin remodeler DECREASED IN DNA METHYLATION (DDM1) prevented the exchange between the histone variants H2A.Z and H2A.W over transposons resulting in their enrichment in chromatin states found only on proteins coding genes in the wild type. Hence, the dynamics of histone H2A variants exchange impacted the definition and distribution of chromatin states. We propose that dynamics of histone variants control the organization of histone modifications into chromatin states to achieve landmarks that signify the ability for transcription.
Chromatin immunoprecipitation sequencing (ChIP-seq) for histone H2A variants and histone modifications in Col0 and ddm1(-/-) .

overall_design: ChIP-seq for Histone Variant and histone modifications WT and ddm1(-/-) was performed with 2 or more biological replicates each.


title: ChIP-seq for Histone variants and Histone modifictaions

type: Genome binding/occupancy profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Transcriptome analysis of allospecific CD8 T cells in murine pregnancy or graft rejection

status: Public on May 03 2023

city: Chicago

first: Anita

last: Chong

state: IL

address: 5841 S Maryland Ave

country: USA

institute: University of Chicago

type: Expression profiling by high throughput sequencing

summary: RNAseq analysis of CD8 T cells after pregnancy-induced tolerance/hypofunction. The goal of this experiment was to compare the transcriptional effect of pregnancy on naive vs. memory fetus-specific CD8 T cells. We also included naive and skin-sensitized CD8 T cells (without pregnancy) as controls.

overall_design: T cells were sorted by flow cytometry and RNA-seq was performed.

first: Pollard

last: Jared

first: Yin

last: Dengping

first: Chong

last: Anita


title: Loss of interleukin-1 beta is not protective in the lupus-prone NZM2328 mouse model

status: Public on Apr 30 2023

city: Ann Arbor

first: Lam

last: Tsoi

state: MI

address: Medical Sciences 1 Bldg. 1301 E. Catherine

institute: University of Michigan

summary: RNA-sequencing analysis identified upregulation of TNF and IL-17 signaling pathways specifically in females lacking IL-1β. Increases in these signaling pathways are also found in female patients with lupus nephritis, suggesting clinical relevance for upregulation of these pathways.

overall_design: To better understand the impact of IL-1β deletion on lupus kidneys, genome-wide transcriptome analysis using RNA-sequencing (RNA-seq) was performed and transcriptional differences in the kidneys of male and female NZM and NZM-Il1b-/- mice were examined. Kidney RNA was isolated via Zymo Direct-zol RNA isolation kit and libraries were generated using standard poly-A prep kits (New England Biolabs) with the assistance of the U-M Advanced Genomics Core.

first: J

middle: M

last: Kahlenberg

first: Shannon

middle: N

last: Estadt

middle: C


title: Levo-tetrahydropalmatine Ameliorates Neuropathic Pain via Suppressing the Activation of the Clec7a-MAPK/NF-κB-NLRP3 Inflammasome Axis

status: Public on May 05 2023

city: Beijing

first: Wu

last: Dan

address: Dongzhimennei south steet 16

country: China

institute: Institute of Chinese Materia Medica，China Academy of Chinese Medical Sciences

summary: Due to the complex pathogenesis of neuropathic pain (NP), the therapeutic effect of existing drugs on NP is not satisfactory, which seriously affects the life quality of patients. Accumulating studies have indicated that neuroinflammation in the spinal cord may play a vital role in NP development and progression. Levo-tetrahydropalmatine (l-THP) has been extensively used for the treatment of a variety of chronic pain for decades. However, the analgesic effects and the underlying mechanisms of I-THP against NP have not been fully elucidated. To address this problem, we herein carried out RNA-seq and bioinformatics analyses to identify the effective target profiling of I-THP including 1113 upregulated and 132 downregulated genes in spinal cord obtained from Chronic constrictive injury (CCI) rats with or without I-THP administration.

overall_design: SC tissues (L4-L6) collected from the rats in the Sham, CCI and CCI+THP groups (n=4 per group) on postoperative day 10 were immersed in TRIzol (Invitrogen, CA, USA) and immediately frozen in liquid nitrogen for the detection.Sequencing libraries were generated using NEBNextUltra RNA Library Prep Set for Illumina (NEB, USA.). The clustering of the index-coded samples was performed on a cBot Cluster Generation System using TruSeq SR Cluster Kit v3-cBot-HS (Illumia). After cluster generation, the library preparations were sequenced on an Illumina Hiseq 2500 platform. Gene expression profiling was analyzed using R (http://www.rproject.org/, version 3.1.1) with Bioconductor packages (http://www.bioconductor.org/). Raw intensities were normalized using Robust multi-array average (RMA method).

first: Dan

last: Wu

first: Chunhui

last: Zhao

first: Haiyu

last: Xu

first: Yanqiong

last: Zhang


title: RNA decay defines the therapeutic response to transcriptional perturbation in leukemia [SLAMseq THP1 RNAPII targeting]

status: Public on Apr 17 2023

city: Melbourne

first: Izabela

last: Todorovski

state: VIC

address: 305 Grattan Street

department: Cancer Research Division

country: Australia

institute: Peter MacCallum Centre

summary: Therapeutic targeting of dysregulated transcriptional programs has arisen as a promising strategy for the treatment of leukemias. The therapeutic response to small molecule inhibitors of Bromodomain-Containing Proteins (BRD), such as BRD2 and BRD4, P300/cAMP-response element binding protein (CBP) and Cyclin Dependent Kinases (CDKs), is generally attributed to the selective disruption of oncogenic gene expression networks driven by enhancers, super-enhancers (SEs) and lineage-specific transcription factors (TFs), including the c-MYC oncogene. Using technologies such as thiol (SH)-linked alkylation for the metabolic sequencing of RNA sequencing (SLAM-seq) to profile messenger RNA (mRNA) decay and production rates, we demonstrate that gene intrinsic properties largely govern the selectivity associated with transcriptional inhibition, where total mRNA response signatures are dominated with genes that have short transcript half-lives, including those regulated by SEs and oncogenic TFs. Further highlighting that gene sensitivities only occur in the context of short transcript half-lives, stabilisation of the c-MYC transcript through changes in the 3’ UTR rendered it insensitive to transcriptional targeting. However, this was not sufficient to rescue c-MYC target gene transcription and anti-leukemia effects following transcriptional inhibition. Importantly, long-lived mRNAs encoding essential genes that evade transcriptional targeting can be rendered sensitive via modulation of mRNA decay kinetics through inhibition of the RNA Binding Protein (RBP), ELAV Like RNA binding protein 1 (ELAVL1)/ Human Antigen R (HuR). Taken together, these data demonstrate that mRNA decay shapes the therapeutic response to transcriptional perturbation and can be modulated for novel therapeutic outcomes using transcriptional agents in leukemia.

overall_design: THP-1 cells (1 x 10^6 per treatment) were first pre-treated with small molecule inhibitors for a total time of 2 hours to pre-establish protein-target inhibition. Newly synthesized RNA in THP-1 cells was then labelled using 1mM 4-sU in the final 10 minutes of treatment at 37°C and 5% carbon dioxide.

first: Ricky

middle: W

last: Johnstone

first: Stephin

middle: J

last: Vervoort


title: Targeting stromal cell sialylation reverses T cell mediated immunosuppression in the tumor microenvironment

status: Public on May 22 2023

city: Galway

first: Aideen

last: Ryan

address: University Road

country: Ireland

institute: National University of Ireland, Galway

summary:
Immunosuppressive tumor microenvironments (TME) reduce the effectiveness of immune responses in cancer. Mesenchymal stromal cells (MSC), precursors to cancer-associated fibroblasts (CAFs), dictate tumor progression by enhancing immune cell suppression in colorectal cancer (CRC). Hyper-sialylation of glycans promotes immune evasion in cancer through binding of sialic acids to their receptors, Siglecs, expressed on immune cells that results in inhibition of effector functions. The role of sialylation in dictating MSC/CAF immunosuppression in the TME is unknown.
In this study, we show that tumor-conditioned stromal cells have increased sialyltransferase expression, α2,3/6-linked sialic acid and Siglec ligands. Tumor-conditioned stromal cells and CAFs induce exhausted immunomodulatory PD-1, Siglec-7 and Siglec-9-expressing T cell phenotypes. In vivo, targeting stromal cell sialylation reverses stromal cell-mediated immunosuppression, as evidenced by infiltration of CD25 and granzyme B-expressing T cells in the tumor and draining lymph node. Targeting stromal cell sialylation may overcome immunosuppression in the CRC TME.

overall_design: RNA sequencing of untreated murine mesenchyaml stromal cells (MSCs) (n=3) compared to CT26 tumor conditioned media (TCM)-conditioned MSCs (n=3)

first: Oliver

last: Treacy


title: Epigenetic analysis of allospecific CD8 T cells in murine pregnancy or graft rejection

first: Anita

last: Chong

summary: ATAC-seq analysis of CD8 T cells after pregnancy-induced tolerance/hypofunction. The goal of this experiment was to compare the epigenetic effect of pregnancy on naive vs. memory fetus-specific CD8 T cells. We also included naive and skin-sensitized CD8 T cells (without pregnancy) as controls.

overall_design: T cells were sorted by flow cytometry and ATAC-seq was performed.


title: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone H2A variants and histone modifications in WT Col-0 seedlings.

first: Bhagyshree

last: Jamge

summary:
How histone intrinsic sequence variation or regulatory modifications regulate nucleosome interactions with transcription remain unclear. To clarify this question, we examined how histone variants and histone modifications assemble in the Arabidopsis thaliana genome, identifying a limited number of chromatin states that divide euchromatin and heterochromatin in biologically significant subdomains. We showed that histone variants were as significant as histone modifications to determine the composition of chromatin states. The loss of function of the chromatin remodeler DECREASED IN DNA METHYLATION (DDM1) prevented the exchange between the histone variants H2A.Z and H2A.W over transposons resulting in their enrichment in chromatin states found only on proteins coding genes in the wild type. Hence, the dynamics of histone H2A variants exchange impacted the definition and distribution of chromatin states. We propose that dynamics of histone variants control the organization of histone modifications into chromatin states to achieve landmarks that signify the ability for transcription.
Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone H2A variants and histone modifications in seedlings .

overall_design: Each set has its own Input and H3


title: Analysis of allospecific CD8 T cells in murine pregnancy or graft rejection


title: RNA decay defines the therapeutic response to transcriptional perturbation in leukemia [TotalRNAseq K562 MYC clones]

overall_design: K562 HDR-edited cells (1 x 10^6 per treatment) were treated with small molecule inhibitors for a total time of 6 hours at 37°C and 5% carbon dioxide.


title: RNA decay defines the therapeutic response to transcriptional perturbation in leukemia [SLAMseq THP1 decay rates]

overall_design: THP-1 cells were treated with 30μM 4-thiouridine for 12 hours at 37°C and 5% carbon dioxide, whereby culture medium was exchanged every 3 hours for the duration of the pulse.  THP-1 cells were then washed in sterile ice-cold PBS twice and resuspended in pre-warmed (37°C) culture medium containing 3mM uridine. THP-1 cells were then harvested at 0- , 0.3-, 0.6-, 1-, 2-, 8-, 12- hours post-uridine chase.


title: RNA decay defines the therapeutic response to transcriptional perturbation in leukemia [MACseq_K562]

overall_design: K562 cells (5 x 10^4 per well) in a final volume of 100μL in a 96-well plate format were incubated with transcriptional and epigenetic inhibitors in technical duplicate for 6 hours at 37°C and 5% carbon dioxide.


title: RNA decay defines the therapeutic response to transcriptional perturbation in leukemia [3mRNAseq THP1 ELAVL1 WT and KO]

overall_design: THP1 Cas9 cells expressing non-targeting control sgRNA (SCR) or sgRNA targeting ELAVL1 (ELAVL1 KO) were treated with DMSO or 100nM AZ-5576 for 6 hours at 37°C and 5% carbon dioxide.


title: RNA decay defines the therapeutic response to transcriptional perturbation in leukemia [SLAMseq K562 decay rates + drug]

overall_design: K562 cells were treated with 30μM 4-thiouridine for 12 hours at 37°C and 5% carbon dioxide, whereby culture medium was exchanged every 3 hours for the duration of the pulse.  K562 cells were then washed in sterile ice-cold PBS twice and resuspended in pre-warmed (37°C) culture medium containing 3mM uridine and either DMSO, 1μM JQ1 or 1μM AZ-5576. K562 cells were then harvested at 0- , 2-, 4-, 8- hours post-uridine chase.


title: RNA kinetics influence the response to transcriptional perturbation in leukaemia cell lines


title: Distinct tumor architectures for metastatic colonization of the brain [scRNA-seq]

status: Public on May 02 2023

city: New York

first: Siting

last: Gan

state: NY

address: 417 East 68th Street

department: SKI

institute: MSKCC

summary: Brain metastasis is a dismal complication of cancer that hinges on the initial survival and outgrowth of disseminated cancer cells. To better understand these crucial early stages of brain metastatic colonization, we investigated two prevalent sources of cerebral relapse in the clinic, triple-negative breast cancer (TNBC) and HER2+ breast cancer (HER2BC). We elucidated distinctive early tumor architectures, physical and functional stromal interfaces, and autocrine growth programs employed by these two tumor types to colonize the brain. TNBC cells form extensive perivascular sheath colonies with diffusive contact with astrocytes and microglia. In striking contrast, heightened autonomous deposition of several extracellular matrix components prompts HER2BC cells to colonize the brain as compact, spheroidal colonies, segregating stromal cells to the periphery of the colony. Single-cell dissection of the spatially resolved tumor microenvironment (TME) reveals that brain metastases activate – to different degrees – the canonical stages of the disease-associated microglia (DAM) response previously defined in Alzheimer’s disease. Differential engagement of paracrine tumor-DAM signaling through the receptor AXL suggests specific pro-metastatic functions of the tumor architecture in both TNBC perivascular and HER2BC spheroidal colonies. Collectively, our findings illuminate the distinct stereospatial features of two different yet highly efficient modes of brain colonization, and the relevance of these features in future efforts to leverage the TME to treat brain metastasis.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design:
Xenograph model mice were injected with MDA231-BrM or HCC1954-BrM cells and brains were harvested after 30 days of growth for scRNA-seq.

Additional processed data files required to run the code uploaded to GitHub (https://github.com/dpeerlab/Brain-metastasis-TME) are deposited in Zenodo (https://doi.org/10.5281/zenodo.13863738).

first: Danilo

middle: G

last: Macalinao

first: Sayyed

middle: H

last: Shahoei

first: Lin

last: Tian

first: Xin

last: Jin

first: Harihar

last: Basnet

first: James

middle: T

last: Muller

first: Pranita

last: Atri

first: Evan

last: Seffar

first: Walid

last: Chatila

first: Anna-Katerina

last: Hadjantonakis

first: Nikolaus

last: Schultz

first: Edi

last: Brogi

first: Tejus

middle: A

last: Bale

first: Dana

last: Pe'er

first: Joan

last: Massagué


title: RNA decay defines the therapeutic response to transcriptional perturbation in leukemia [SLAMseq K562 RNAPII targeting]

first: Izabela

last: Todorovski

overall_design: K562 cells (1 x 10^6 per treatment) were first pre-treated with small molecule inhibitors for a total time of 2 hours to pre-establish protein-target inhibition. Newly synthesized RNA in K562 cells was then labelled using 100 μM 4-sU in the final 1 hour of treatment at 37°C and 5% carbon dioxide.

first: Ricky

last: Johnstone

first: Stephin

last: Vervoort


title: RNA decay defines the therapeutic response to transcriptional perturbation in leukemia [SLAMseq K562 decay rates]

overall_design: K562 cells were treated with 30μM 4-thiouridine for 12 hours at 37°C and 5% carbon dioxide, whereby culture medium was exchanged every 3 hours for the duration of the pulse.  K562 cells were then washed in sterile ice-cold PBS twice and resuspended in pre-warmed (37°C) culture medium containing 3mM uridine (Sigma Aldrich, U6381). K562 cells were then harvested at 0- ,1-, 2-, 4-, 8-, 12- hours post-uridine chase.


title: lncRNA HOTAIRM1 Facilitates Nasopharyngeal Carcinoma Resistance to Irradiation and Ferroptosis by Increasing SLC7A11 Stability and Expression via METTL3-mediated m6A Methylation

status: Public on Apr 12 2023

city: Changchun

first: Tongjian

last: Zhao

address: 1266 Fujin Road

institute: School of Pharmaceutical Sciences, Jilin University

summary: Radiotherapy has become a main treatment for patients with nasopharyngeal carcinoma (NPC), who often develop residual or recurrent tumors due to radioresistance. The lncRNA HOTAIRM1 plays crucial roles in the formation and development of various cancers, but the interaction between HOTAIRM1 and radioresistant NPC remains unclear. In this study, we evaluated the potential of HOTAIRM1 as a biomarker of NPC radioresistance. Proliferation, apoptosis, DNA damage, and RNA-seq analyses were conducted to examine the mechanisms by which HOTAIRM1 contributes to NPC radioresistance, and in vivo experiments were performed using nude mice. Our findings indicated that HOTAIRM1 levels were upregulated in radioresistant NPC tissues and cell lines. High HOTAIRM1 expression was associated with increased NPC cell proliferation, decreased apoptosis, and decreased cellular DNA damage after radiotherapy. Mechanistically, HOTAIRM1 promoted NPC radioresistance by increasing SLC7A11 stability and expression through METTL3-mediated m6A demethylation. Additionally, high HOTAIRM1 expression decreased SLC7A11-associated ferroptosis. Our findings demonstrate that HOTAIRM1 promotes METTL3-mediated m6A methylation to increase SLC7A11 expression and stability, thereby inhibiting ferroptosis to trigger NPC radioresistance. This novel molecular mechanism underlying the role of HOTAIRM1 in the regulation of radioresistant NPC may aid in the identification of biomarkers and therapeutic targets for the treatment of radioresistant NPC.

overall_design: The total RNA of C666-1R-shNC and C666-1R-shHOTAIRM1 was isolated and purified. RNA libraries were sequenced on the Illumina NovaSeq 6000 platform at Huayin Health Medical Group Co., Ltd. (Guangzhou, China). Differentially expressed genes (DEGs) were identified based on a cutoff p-value < 0.05 and | logFC| > 1.

first: Jinglin

last: Mi

first: Weimei

last: Huang

first: Zhixun

last: Li

first: Rensheng

last: Wang


title: RNA-Seq and snRNA-seq analysis of Sleep deprivation in Wildtype Mice

city: Spokane

first: Lucia

last: Peixoto

state: WA

address: PO Box 1495

department: College of Medicine

institute: Washington State University, Spokane

summary: This dataset constitutes the first snRNA-Seq study of gene expression following sleep deprivation in wildtype mice with paralell bulk-RNA-seq data. In addition it contains RNA-seq analysis of the effect of recovery sleep following sleep deprivation

overall_design: 16 total samples were analyzed. Pre-frontal cortex tissue was collected at 5 hours of sleep deprivation (SD5, E). Animals that were left to sleep in their homecage were dissected at the same time of day to control for variations due to circadian rhythms (HC5, C).

first: Davide

last: Risso

first: Stephanie

last: Hicks

first: Kaitlyn

last: Ford

first: Zuin

last: Elena


title: RNA decay defines the therapeutic response to transcriptional perturbation in leukemia [TTseq K562 production rates]

overall_design: K562 cells (5 x 10^7 per treatment condition) were incubated with 1mM 4-thiouridine for either 5 or 15 minutes at 37°C and 5% carbon dioxide.


title: Cross-species regulatory landscapes and elements revealed by novel joint systematic integration of human and mouse blood cell epigenomes [human ChIP]

status: Public on Apr 10 2023

city: University Park

first: Ross

last: Hardison

state: PA

address: 303 Wartik Lab

institute: Pennsylvania State University

summary: Knowledge of the locations and activities of cis-regulatory elements (CREs) is needed to decipher basic mechanisms of gene regulation and to better understand the impact of genetic variants on complex traits. Previous studies identified candidate CREs (cCREs) using multiple epigenetic features in cell types from one species at a time, but such an approach can make it difficult to compare results across species. In contrast, we conducted a cross-species study defining epigenetic states and identifying cCREs in blood cell types to generate maps of the regulatory landscapes and cCREs that are comparable across species. This study used integrative modeling of eight epigenetic features jointly in both human and mouse in our Validated Systematic Integration (VISION) Project. The accuracy of the cCRE predictions was supported by orthogonal function-related data. The contribution of each epigenetic state in cCREs to gene regulation was estimated from a multivariate regression against gene expression across cell types, and these values were used to estimate an epigenetic state Regulatory Potential (esRP) score for each cCRE in each cell type. These esRP scores have broad utility for visualizing and categorizing the dynamic changes in cCREs during hematopoietic differentiation. After jointly clustering cCREs based on their esRP scores across human and mouse cell types, we found distinctive transcription factor binding motifs associated with each group of cCREs with similar patterns of regulatory activity; these associations are similar between human and mouse. Genetic variants associated with blood cell phenotypes (from the GWAS Catalog and the UK Biobank study) were highly and specifically enriched in the catalog of human VISION cCREs, indicating the utility of our cCRE predictions for understanding the impact of noncoding genetic variants on both physiologic and pathologic blood cell-related traits. The cross-species joint modeling enabled a comparison of cCREs that revealed both conserved and lineage-specific patterns of epigenetic evolution, even in the absence of genomic sequence alignment. The VISION project resources are accessible through a suite of tools and browsers at http://usevision.org.

overall_design: This paper reports an integrative analysis of genome-wide epigenetic data sets from progenitor and mature blood cell types jointly from human and mouse. A total of 404 data sets were used as input data for the integrative analysis, of which 216 were from human cell types and 188 were from mouse cell types. Most of the data used have been previously published. Many but not all of the previously published datasets have biological replicates. We also generated new data for multiple features in specific cell types to have more complete coverage of the epigenetic landscape across the cell types.

first: Yong

last: Cheng

first: Yichao

first: Qian

last: Qi

first: Yanghua

last: He


title: Cross-species regulatory landscapes and elements revealed by novel joint systematic integration of human and mouse blood cell epigenomes [mouse histones]

overall_design: This paper reports an integrative analysis of genome-wide epigenetic data sets from progenitor and mature blood cell types jointly from human and mouse. A total of 404 data sets were used as input data for the integrative analysis, of which 216 were from human cell types and 188 were from mouse cell types. Most of the data used have been previously published. Many but not all of the previously published datasets have biological replicates. We also generated new data for multiple features in specific cell types to have more complete coverage of the epigenetic landscape across the cell types. For ChIP-seq of histone modifications in immature megakaryocytes (iMK), we are submitting biological replicates of H3K4me1 and H3K27me3 and one determination of H3K9me3. In adult erythroblasts, we are submitting one determination of H3K4me1.

first: Cheryl

last: Keller

first: Belinda

last: Giardine

first: Amber

last: Miller

first: David

last: Bodine

first: Stacie

last: Anderson

first: Elisabeth

middle: F

last: Heuston


title: Cross-species regulatory landscapes and elements revealed by novel joint systematic integration of human and mouse blood cell epigenomes

overall_design: Refer to individual Series


title: Cross-species regulatory landscapes and elements revealed by novel joint systematic integration of human and mouse blood cell epigenomes [mouse TFbs]

overall_design: This paper reports an integrative analysis of genome-wide epigenetic data sets from progenitor and mature blood cell types jointly from human and mouse. A total of 404 data sets were used as input data for the integrative analysis, of which 216 were from human cell types and 188 were from mouse cell types. Most of the data used have been previously published. Many but not all of the previously published datasets have biological replicates. We also generated new data for multiple features in specific cell types to have more complete coverage of the epigenetic landscape across the cell types. For ChIP-seq of CTCF, we are submitting replicate data from G1E-ER4+E2 cells and one determination in G1E cells, along with the no-antibody "input" control files for each cell line.

first: Marit

last: Vermunt

first: Jing

last: Luan

first: Gerd

last: Blobel


title: Single-cell transcriptome atlas of mammalian hair cells uncovers the molecular mechanisms underlying tonotopic differences

status: Public on Mar 28 2023

city: nanjing

first: Xiangyu

last: Ma

state: JIANGSU

address: No. 2, Sipai Building, Dashiqiao Community, Xinjiekou Street, Xuanwu District, Nanjing

institute: Southeast University

summary: our study discloses the mechanisms underlying the tonotopic map establishment and maintenance in mammalian HCs, and provides an important foundation for further elaborating the mechanisms of HCs in response to different frequencies.

overall_design: Comparing the molecular composition and molecular function of hair cells in different parts of the cochlea. Each sample represents a single cell.

first: Xin

last: Chen


title: Single-cell dissection of human hematopoietic reconstitution after allogeneic hematopoietic stem cell transplantation

status: Public on Mar 18 2023

city: Tianjin

first: Tao

address: 288 Nanjing Road

institute: Institute of Hematology and Blood Diseases Hospital

summary: 10,776 Lin-CD34+ cells and 317,677 total nucleated cells (TNCs) were captured by Single cell RNA sequencing from healthy control, transplant patients and their grafts. We serially profiled the transcriptome of transplanted HSPCs and TNCs to evaluate the hematopoietic process and regulatory mechanisms involved in reconstitution of HSPCs and their daughter cells post-HSCT. Notably, transcriptomic analysis enabled us to observe that immunoregulatory neutrophil progenitors (S100Ahigh Neus) were enriched in granulocyte colony-stimulating factor-mobilized peripheral blood stem cells.

overall_design:
Single cell RNA sequencing were performed in BM and PB samples from 10 transplant patients and their G-CSF grafts.
***The raw data are stored in Genome Sequence Archive (GSA) with accession number HRA001359.***

first: T

first: H

last: Sha

first: E

last: Jiang


title: Environmental conditioning by type I interferons poises naive CD4+ T cells for transition to precursor central memory cells

status: Public on Mar 22 2023

first: Herman

last: Gudjonson

address: 417 E 68th St

department: Computational and Systems Biology Program, SKI

institute: Memorial Sloan Kettering Cancer Center

summary: Upon antigenic stimulation, naïve CD4+ T cells differentiate into phenotypically distinct T helper cells. Naïve T cells are considered homogenous save for their unique T cell receptor (TCR), thought to confer distinct differentiation potential according to its affinity for cognate antigen. Here we show that naïve T cells are transcriptionally heterogeneous and identify a role for type I interferon (IFN) in shaping this heterogeneity. Using complementary single cell analyses, we show that T cell fate is independent of TCR and identify a role for type I IFN signaling in regulating the early differentiation of naïve CD4 T cells towards central memory precursors. Thus, naïve CD4 T cell differentiation potential is determined by environmental cues both prior to and during priming. IFN-conditioned naïve CD4 T cells are expanded in human viral infection and autoimmunity highlighting the relevance of this pathway to beneficial and maladaptive T cell responses, as well as its therapeutic potential for enhanced T cell memory formation.

overall_design: Single-cell RNA sequencing was performed on mouse splenic CD4 T cells. Naïve CD4 T cells from transgenic TCR (tgTCR) Smarta and C7 mice (two replicates each) were adoptively transferred into congenic recipients and profiled at steady state along with host naïve CD4 T cells. To study in vivo C7 differentiation, adoptively transferred tgTCR C7 T cells were profiled 16hr (two replicates) and 40hr post L. monocytogenes-ESAT infection. Additionally, gp66:I-Ab tetramer+ T cells were sorted from an Lm-gp66 infected mouse 7 days post intravenous infection (two replicates) and profiled with single-cell 5' RNA-seq + TCR-seq.

first: Chrysothemis

last: Brown

first: Deeksha

last: Deep

first: Roshan

last: Sharma

first: Seunghee

last: Hong

first: Saskia

last: Hemmers

first: Michail

last: Schizas

first: Zhong

last: Wang

first: Yuezhou

first: Duane

middle: R

last: Wesemann

first: Virginia

last: Pascual

first: Dana

last: Pe’er

first: Alexander

middle: Y

last: Rudensky


title: Consequences of collagen induced inflammatory arthritis on circadian regulation of the gut microbiome.

status: Public on Mar 15 2023

city: Manchester

first: Julie

middle: Elizabeth

last: Gibbs

address: Oxford Road

department: FBMH

country: United Kingdom

institute: University of Manchester

summary: Autoimmune diseases, such as rheumatoid arthritis, are associated with significant gut microbiota dysbiosis.  Here we show that remodelling of 24h rhythms within the gut during inflammatory joint disease drives profound changes in the microbiome and gut permeability.

overall_design: RNA-Seq from mRNA of mouse colon 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.

middle: E

first: Devin

last: Simpkins

first: Polly

last: Downton

first: Kathryn

last: Gray

first: Suzanna

last: Dickson

first: Robert

last: Maidstone

first: Joanne

last: Konkel

first: Matthew

last: Hepworth

first: David

last: Ray

last: Bechtold


title: Loss of Dnajc21 leads to cytopenia and altered nucleotide metabolism in zebrafish

status: Public on Mar 01 2023

city: Ottawa

first: Sergey

last: Prykhozhij

state: ON

address: Room 318/319 | CAREG, 20 Marie-Curie Private

country: Canada

institute: CHEO Research Institute/University of Ottawa

summary: Mutations in the DNAJC21 gene were recently described in Shwachman-Diamond syndrome (SDS), a bone marrow failure syndrome with high predisposition for myeloid malignancies. To study the underlying biology in hematopoiesis regulation and disease, we generated the first in vivo model of Dnajc21 deficiency using zebrafish. Zebrafish dnajc21 mutants phenocopy key SDS patient phenotypes such as cytopenia, reduced growth and defective ribosome biogenesis. We show that cytopenia results from impaired hematopoietic differentiation and cell proliferation, and is accompanied by an expansion of hematopoietic stem and progenitor cells during both embryonic and adult hematopoiesis. The introduction of a tp53 point mutation in the dnajc21 mutants results in myelodysplastic syndrome with erythroid dysplasia as early as four months of age. Using transcriptomic and metabolomic analyses, we show that Dnajc21 regulates various metabolic pathways including nucleotide biosynthesis. Chemical modulation of the pyrimidine biosynthesis pathway in dnajc21 mutants reveals an association with neutrophil differentiation, suggesting a novel mechanism in dnajc21-mutant SDS biology.

overall_design: Gene expression profiling through RNA sequencing of wildtype and dnajc21 mutant zebrafish at 48 hours post-fertilization (hpf)

first: S

last: Ketharnathan

middle: V


title: genomic profiling of mouse CD8 T cells electroporated with non-targeting or AR-specific gRNAs

city: Portland

first: Zheng

last: Xia

state: Oregon

address: 3181 SW Sam Jackson Park Rd

department: Department of Biomedical Engineering

institute: Oregon Health & Science University

summary:
Purpose: Determine the change in expression of genes in AR deficient CD8 T cells
Methods: C57Bl/6J splenocytes were isolated, total CD8 T cells magnetically enriched and electroporated with non-targeting gRNA or AR-specific gRNAs. Cells were stimulated with aCD3/28 for three days before isolating RNA and library prep. Sequencing was performed by the Massively Parallel Sequencing Shared Resource (MPSSR) at OHSU.
Results: AR regulated genes in mouse CD8 T cells.

overall_design: Bulk RNA-seq of murine CD8 T cells from control and AR-deficient T cells.

first: Amy

last: Moran


title: A global transcriptome analysis of human dermal fibroblasts upon knockdown or overexpression of the circular RNAs circGLIS3 (circBase ID: hsa_circ_0002874)

status: Public on Feb 06 2023

city: Stockholm

first: Yongjian

last: Chen

address: Solnavägen 1

country: Sweden

institute: Karolinska Institutet

summary: In an RNAseq analysis, we have identified circGLIS3 with high levels acute wound dermis compared to skin. The biological function of circGLIS3 in human dermal fibroblasts during wound repair has not been studied. To study the genes regulated by circGLIS3, we transfected siRNA or plasmid into human dermal fibroblasts to knockdown or overexpress circGLIS3. We performed a global transcriptome analysis of fibroblasts upon circRNA knockdown or overexpression using Affymetrix arrays.

overall_design: Gene expression profiling of fibroblasts transfected with siRNA control (n = 3), si-circGLIS3 (n = 3), p-Ctrl (n = 2), p-circGLIS3 (n = 2) or p-circGLIS3_RNA (n = 2) for 24 hours was carried out by using human Clariom™ S assay (ThermoFisher Scientific) at the Bioinformatics and Expression Analysis (BEA) core facility at Karolinska Institutet.

first: Ning

middle: X

last: Landén

first: Maria

last: Toma


title: Neutralization of Acyl-CoA Binding Protein Confers Autophagy-Dependent Organ Protection

status: Public on Feb 24 2023

city: PARIS

first: Guido

last: Kroemer

address: 15 rue de L'école de médecine

country: France

institute: Centre de Recherche des Cordeliers

summary: Total liver RNA extracts from adult male mice (8 weeks old, C57BL/6) injected with monoclonal anti-ACBP/DBI (1 dose per week) and subjected to Methionine and Choline Deficient Diet  (regime duration: 4weeks) were analyzed to describe the effect of neutralization of ACBP/DBI to NASH-induced transcriptomic alterations.

overall_design: Regular Chow Diet+Antibody IgG, C57BL/6 (n=5), Regular Chow Diet+Antibody anti-ACBP/DBI, C57BL/6 (n=5), Methionine and Choline Deficient Diet+Antibody IgG, C57BL/6 (n=5), Methionine and Choline Deficient Diet+Antibody anti-ACBP/DBI, C57BL/6 (n=5).

first: Omar

last: Motino

first: Vincent

last: Carbonnier


title: Massively parallel characterization of insulator activity across the genome [insulator_libraries]

status: Public on Jan 27 2023

city: Saint Louis

first: Barak

last: Cohen

state: MO

address: 4515 Mckinley Ave

institute: Washington University in St. Louis

summary: Insulators are cis-regulatory sequences (CRSs) that can block enhancers from activating target promoters or act as barriers to block the spread of heterochromatin. Their name derives from their ability to ‘insulate’ transgenes from genomic position effects, an important function in gene therapy and biotechnology applications that require high levels of sustained transgene expression. In theory, flanking transgenes with insulators protects them from position effects, but in practice, efforts to insulate transgenes meet with mixed success because the contextual requirements for insulator function in the genome are not well understood. A key question is whether insulators are modular elements that can function anywhere in the genome or whether they are adapted to function only in certain genomic locations. To distinguish between these two possibilities we developed MPIRE (Massively Parallel Integrated Regulatory Elements) and used it to measure the effects of three insulators (A2, cHS4, ALOXE3) and their mutants at thousands of locations across the genome. Our results show that each insulator functions in only a small number of genomic locations, and that insulator function depends on the sequence motifs that comprise each insulator. All three insulators can block enhancers in the genome, but specificity arises because each insulator blocks enhancers that are bound by different sets of transcription factors. In contrast, only ALOXE3 can act as a heterochromatin barrier. We conclude that insulator function is highly context dependent and that MPIRE is a robust and systematic method for revealing the context dependencies of insulators and other cis-regulatory elements across the genome.

overall_design: Barocde sequencing from genome-integrated massively parallel reporter assays

first: Clarice

last: Hong

first: Alyssa

last: Erickson

first: Li

last: Jie

first: Arnold

last: Federico


title: Single molecule-level metabolic responsive landscape of human liver transcriptome

status: Public on Feb 01 2023

city: Bethesda

first: Haiming

last: Cao

state: MD

address: 9000 Rockville Pike

department: NHLBI

institute: NIH

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


title: Super-sized clustered loops anchored at transposon Helitrons in Xenopus tropicalis sperm associate with late gene expression during embryogenesis [ChIP-Seq2]

status: Public on Jan 26 2023

city: Shenzhen

first: Chuihui

last: Hou

state: Guangdong

address: Xueyuan Avenue

institute: Southern University of Science and Technology

summary: Vertebrate sperm genome differs from somatic cells and undergoes dramatic transformation after fertilization. However, the functional implications of the sperm genome structures have not been fully investigated. Here we show, in the sperms of Xenopus tropicalis, tens of genomic regions harbor multi-megabases, super-sized clustered loops (SSCLs) whose anchors are enriched with Helitrons, the only group of rolling-circle transposons. SSCL anchors are inaccessible and absent of active histone modifications, implying that SSCLs are repressive in nature. Moreover, genes associated with SSCL anchors express late during development, suggesting 3D structure in sperm may associate with gene expression control during embryo development. The absence of CTCF and RNAPII at SSCL anchors argues against CTCF-mediated or transcription-related looping for the SSCLs establishment. Furthermore, our molecular simulation excludes looping and supports a phase separation model through which SSCLs may form. Taken together, our work reveals a previously undiscovered, repressive 3D structure in sperm that may mediate intergenerational gene regulation.

overall_design: Xenopus tropicalis sperm and Xenopus tropiclis x Xenopus laevis hybrid staged embryos were obtained. Hi-C, ChIP-seq, ATAC-seq and RNA-seq were performed in these cells.

first: Chunhui

last: Li

first: Longjian

last: Niu

first: Jinsheng

last: Xu


title: Super-sized clustered loops anchored at transposon Helitrons in Xenopus tropicalis sperm associate with late gene expression during embryogenesis [Hi-C 2]

overall_design: Xenopus tropicalis sperm, Xenopus laevis sperm, and Xenopus tropiclis x Xenopus laevis hybrid staged embryos were obtained. Hi-C, ChIP-seq, ATAC-seq and RNA-seq were performed in these cells.


title: Massively parallel characterization of insulator activity across the genome [pilot_rBC]


title: Massively parallel characterization of insulator activity across the genome [GWLP_pools]


title: Super-sized clustered loops anchored at transposon Helitrons in Xenopus tropicalis sperm associate with late gene expression during embryogenesis [Hi-C]

sample_organism:
Xenopus tropicalis
Xenopus tropicalis x Xenopus laevis

overall_design: Xenopus tropicalis sperm and Xenopus tropicalis x Xenopus laevis hybrid staged embryos were obtained. Hi-C, ChIP-seq, ATAC-seq and RNA-seq were performed in these cells.


title: Transcriptome of the chicken chorioallantoic membrane from male and female embryos, after 11 and 15 days of incubation

status: Public on Jan 20 2023

city: Nouzilly

first: Sophie

last: REHAULT-GODBERT

address: INRAE Centre Val de Loire, UMR BOA

institute: INRAE

summary: The aim the the sequencing project was to investigate differentially expressed genes between fertilized eggs incubated during 11 or 15 days of incubation (EID11 and EID15). At each stage (EID11 and EID15), chorioallantoic membranes from 10 male embryos and 10 females embryos were collected and processed for RNA extraction and RNAseq analysis (n=40 in total). Thus, the design of the protocol also allowed comparison of differentially expressed genes in the chorioallantoic membrane between male and female embryos

overall_design: mRNA profiles of the chorioallantoic membrane between 11 and 15 days of incubation (ROSS 308 broiler line)

first: Maeva

last: Halgrain

last: Réhault-Godbert


title: Super-sized clustered loops anchored at transposon Helitrons in Xenopus tropicalis sperm associate with late gene expression during embryogenesis [ATAC-Seq]


title: Cross-species regulatory landscapes and elements revealed by novel joint systematic integration of human and mouse blood cell epigenomes [human RNA]

first: Ross

last: Hardison

overall_design: This paper reports an integrative analysis of genome-wide epigenetic data sets from progenitor and mature blood cell types jointly from human and mouse. A total of 404 data sets were used as input data for the integrative analysis, of which 216 were from human cell types and 188 were from mouse cell types. Most of the data used have been previously published. Many but not all of the previously published datasets have biological replicates. We also generated new data for multiple features in specific cell types to have more complete coverage of the epigenetic landscape across the cell types.

first: Yong

last: Cheng

first: Yichao

first: Qian

last: Qi

first: Yanghua

last: He


title: Super-sized clustered loops anchored at transposon Helitrons in Xenopus tropicalis sperm associate with late gene expression during embryogenesis [ChIP-Seq]


title: Identification of CT-Detected extramural vessel invasion related gene regulatory network

status: Public on Jan 11 2023

city: Beijing

first: Bo

last: Gao

address: No.11 Xizhimen South Street, Beijing, China

department: Department of General Surgery

institute: Peking university people's hospital

summary: Gastric cancer (GC) was a worldwide cancer with high heterogeneity. More than 90% of GC patients in clinical practice were advanced GC, and the radical resection rate was only about 50%. For advanced gastric cancer, there is no specific targeted therapeutic regimen and the prognosis is poor. Extramural vessel invasion(EMVI) was identified as the tumor cells infiltrating through the gastric wall and into the lumen of extramural vessel. CT detected EMVI has been tested as the independent risk factor of the synchronous metastasis and long-term survival. The development of EMVI was believed as a defining characteristic of gastrointestinal cancer in advanced stage. In recent years, approaches and promising results arising from correlation of cancer imaging features with high-throughput data lead to the new research area known as radiogenomics. A significant amount of literatures in radiogenomics are promising to increase precision in diagnosis, assessment of prognosis and prediction of oncologic treatment . In the present study, we performed a CT detected EMVI related gene regulatory network analysis of differentially expressed coding genes in locally advanced GC. We screened the mRNA and their respective gene networks that were involved in the progression of CT detected EMVI.

overall_design: A search of hospital’s histopathologic electronic information system (HIS) was performed to identified 13 patients with locally advanced GC underwent contrast enhanced multiple detectors computed tomography (ceMDCT) and following standard D2 radical gastrectomy were included in this study from January 2018 to January 2019. The adjuvant chemotherapies of the SOX regimen were performed. Follow-ups of every 2-3 months were taken until the progression event happened within 1 year after surgery. EMVI statuses were reviewed on the preoperative ceMDCT images. According to the EMVI score system, 0-2 was identified as the EMVI negative; 3-4 was identified as positive. Of these 13 included patients, there were 7 patients with EMVI positive status and 6 with EMVI negative status. Fresh-frozen cancerous tissue samples of these 13 included patients were collected from the institutional biobank. After the quality control tests, the Illumina NextSeq system was used to sequence the gene expression of these samples.

first: Jin

first: Yi

last: Wang


title: Super-sized clustered loops anchored at transposon Helitrons in Xenopus tropicalis sperm associate with late gene expression during embryogenesis

sample_organism:
Xenopus laevis
Xenopus tropicalis
Xenopus tropicalis x Xenopus laevis

overall_design: Refer to individual Series


title: RNA sequencing to detect the differentially expressed genes in AngII infused mice after Ethoxysanguinarine, Baicalin, Gastrodin or Valsartan treatment

status: Public on Jan 09 2023

city: Fuzhou

first: Jun

last: Peng

state: Fujian

address: 1 Qiuyang Road, Minhou Shangjie

department: Academy of Integrative Medicine

institute: Fujian University of Traditional Chinese Medicine

summary: The goals of this study is to identify the differential expressed genes in cardiac tissue of C57BL/6 mice with or without Angiotensin II (AngII) treatment, and compare the differential expressed genes in the cardiac tissue of Ang II infused C57BL/6 mice after Ethoxysanguinarine (ETH), Baicalin (BAI), Gastrodin (GAS) or valsartan (VAL) treatment. Briefly, the mice (n=30) were randomly divided into 6 groups: control, AngII, AngII + ETH, AngII + BAI, AngII + GAS and AngII + VAL groups (n=5 for each group). Mice in Control and AngII groups were infused with saline and 500 ng/kg/min of AngII respectively, and orally administrated with saline; the mice in AngII + ETH, AngII + BAI and AngII + GAS groups were infused with AngII (500 ng/kg/min) and orally administrated with 5 mg/kg /day of ETH, BAI or GAS daily for total 4 weeks. The mice in AngII + VAL group were infused with AngII (500 ng/kg/min) and orally administrated with 10.4mg/kg /day of VAL. Then the cardiac tissues were used to identify differentially expressed genes among different groups.

overall_design: RNA sequencing was performed with cardiac tissue of  mice in 6 groups: control, AngII, AngII + ETH, AngII + BAI, AngII + GAS and AngII + VAL groups (n=5 for each group) to identify the differently expressed genes and related pathway.

first: Aling

last: Shen

first: Ying

first: Huixin

last: Liu

first: Xiuli

last: Zhang

first: Nanhui


title: Massively parallel characterization of insulator activity across the genome

first: Barak

last: Cohen


title: RNAseq of mitral valves from Fbn1 C1039G/+ mice with or without CCR2 deficiency

status: Public on Jan 01 2023

city: Cincinnati

first: Katherine

last: Yutzey

state: OH

address: 3333 Burnet Ave

institute: Cincinnati Children's Hospital Medical Center

summary: Mitral valves were isolated from 2-month-old mice with the following 4 genotypes: 1) CCR2 RFP/+ (Chet), 2) CCR2 RFP/RFP (Cko), 3) Fbn1 C1039G/+; CCR2 RFP/+ (FhetChet), 4) Fbn1 C1039G/+; CCR2 RFP/RFP (FhetCko). N=4 for each genotype. Total RNA was extracted from mitral valves individually for gene expression profiling.

overall_design: Total RNA from mitral valves of each mouse was used for deep RNA sequencing individually


title: Super-sized clustered loops anchored at transposon Helitrons in Xenopus tropicalis sperm associate with late gene expression during embryogenesis [RNA-Seq]

first: Chuihui

last: Hou

first: Chunhui

first: Li

last: Li

first: Longjian

last: Niu

first: Jinsheng


title: Gene expression profile at single cell level of hematopoietic stem cells from bone marrow in aging mice.

status: Public on Dec 31 2022

city: Los Angeles

first: Jiya

last: Eerdeng

state: CA

address: 1425 San Pablo St

department: DSR

institute: University of Southern California

summary: Age-related physiological decline emerges at different chronological ages across individuals. We compared mice that exhibited early or delayed hematopoietic aging at the same chronological age by scRNA-seq.

overall_design: Hematopoietic stem cells (HSCs) from mice that exhibited early or delayed hematopoietic aging at the same chronological age were analyzed by scRNA-seq.

first: Anna

last: Nogalska


title: RNA-seq expression data identifies metabolic pathways under Gre factor control in Salmonella

city: Aurora

first: Andrés

last: Vázquez-Torres

state: CO

department: Immunology and Microbiology

institute: University of Colorado Anschutz Medical Campus

summary: We report the findings of genes under the transcriptional control of Gre factors by comparing RNA-seq data from parental, wild-type Salmonella enterica enterica Typhimurium 14028s and a ∆greA ∆greB strain. By comparing differential gene expression, we identify a metabolic scheme for responding to oxidative stress that is regulated in part by the action of Gre factors

sample_organism: Salmonella enterica subsp. enterica serovar Typhimurium str. 14028S

overall_design: Salmonella strains (parental, wild-type and a ∆greA ∆greB strain) were grown in MOPS-Glucose minimal medium at 37ºC to an OD600 of 0.25.  Cultures were then pelleted and extracted.

first: Shashi

last: Kant

first: James

last: Till


title: Polarization of human iPSC-derived macrophages directs their immunological response to secondary pro-inflammatory stimuli

status: Public on Dec 22 2022

city: Hannover

first: Maximilian

last: Schinke

address: Nikolai-Fuchs-Str. 1

country: Germany

institute: Fraunhofer ITEM

summary: Transcriptional profiling of human iPSC-derived macrophages polarized for 24 hours with either IFNg, IL-4, IL-10+TGFb or untreated

overall_design: Biological replicates: macrophages were gained from two different differentiation rounds and treated subsequently

first: Schinke

last: Maximilian

first: Ackermann

last: Mania


title: Heterogeneous fates of simultaneously-born neurons during early corticogenesis

status: Public on Dec 18 2022

city: Lausanne

first: Elia

last: Magrinelli

state: Canto Vaud

address: Rue du Bugnon 9

department: Department of Neuroscience

country: Switzerland

institute: University of Lausanne

summary: We labelled isochronic cohorts of mouse cortical neurons and analyzed their contribution to the diversity of cortical neurons. We find that early born neurons contribute to a large diversity of cortical neuron subtypes, asa also confirmed by the transcsriptomic analysis of E13.5 born neurons through Patchseq. Ultimately we identify eaarly differentiation of early born neurons as the instance characterized by the highest tranascriptomical variability which intermingles deep layer identity genes with upper layer specific ones.

overall_design: Analysis of E13.5 born cortical neurons in S1 at P7 through FlashTag labelling followed by collection through Patchseq. Neurons were selected across 5 experiments collecting throughout the whole range of radial position populated by E13.5 born neurons.

first: Natalia

last: Baumann


title: miR-221/222 drive synovial fibroblast expansion and pathogenesis of TNF-mediated arthritis

status: Public on Dec 16 2022

city: Vari

first: George

last: Kollias

state: Attica

address: 34 Fleming Street

department: Institute for Bioinnovation/ Department of Physiology, School of Medicine

country: Greece

institute: BSRC "Alexander Fleming"/ National and Kapodistrian University of Athens

summary: MicroRNAs (miRNAs) constitute fine tuners of gene expression and are implicated in a variety of diseases spanning from inflammation to cancer. miRNA expression is deregulated in rheumatoid arthritis (RA), however, their specific role in key arthritogenic cells such as the synovial fibroblast (SF) remains elusive. We have shown in the past that the expression of the miR-221/222 cluster is upregulated in RA SFs. Here, we demonstrate that miR-221/222 activation is downstream of major inflammatory cytokines, such as TNF and IL-1β, which promote miR-221/222 expression independently. miR-221/222 expression in SFs from the huTNFtg mouse model of arthritis correlates with disease progression. Targeted transgenic overexpression of miR-221/222 in SFs of the huTNFtg mouse model led to further expansion of synovial fibroblasts and disease exacerbation. miR-221/222 overexpression altered the transcriptional profile of SFs igniting pathways involved in cell cycle progression and ECM regulation. Validated targets of miR-221/222 included p27 and p57 cell cycle inhibitors, as well as Smarca1 (a chromatin remodeling component). In contrast, complete genetic ablation of miR-221/222 in arthritic mice led to decreased proliferation of fibroblasts, reduced synovial expansion and attenuated disease. scATAC-seq data analysis revealed increased miR-221/222 gene activity in the pathogenic and activated clusters of the intermediate and lining compartment. Taken together, our results establish an SF-specific pathogenic role of the miR-221/222 cluster in arthritis and suggest that its therapeutic targeting in specific subpopulations should inform the design of novel fibroblast-targeted therapies for human disease.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for wt, huTNFtg, TgColVI-miR-221/222, huTNFtg;TgColVI-miR-221/222 mice. Reference sample: wt mice

first: Fani

last: Roumelioti

first: Christos

last: Tzaferis

first: Dimitris

last: Konstantopoulos

first: Dimitra

last: Papadopoulou

first: Alejandro

last: Prados

first: Maria

last: Sakkou

first: Anastasios

last: Liakos

first: Panagiotis

last: Chouvardas

first: Theodore

last: Meletakos

first: Yiannis

last: Pandis

first: Niki

last: Karagianni

last: Denis

last: Fousteri

first: Marietta

last: Armaka


title: GLK ChIP-seq and ATAC-seq data in Arabidopsis, Tobacco, Tomato, Rice and Maize.

status: Public on Dec 08 2022

city: Hong Kong

first: Sibo

last: REN

address: Sha tin CUHK

institute: The Chinese University of Hong Kong

summary: Comparison of the binding of GOLDEN2-LIKE (GLK) transcription factors in tomato, tobacco, Arabidopsis, maize and rice, show that genome cis-variation caused wide-spread TF binding divergence, and most of the TF binding sites are genetically redundant.

sample_organism:
Arabidopsis thaliana
Solanum lycopersicum
Nicotiana benthamiana
Zea mays
Oryza sativa Japonica Group

overall_design:
Transcription factor was transciently expressed in Arabidopsis, Tobacco, Tomato, Rice and Maize.
Raw data available in PRJNA682315, PRJNA518749, PRJNA743574

first: Silin

last: Zhong

first: Xiaoyu

last: Tu


title: Human striatal glia differentially contribute to AD and PD-specific neurodegeneration

status: Public on Dec 05 2022

city: St. Louis

first: Guoyan

last: Zhao

address: 660 South Euclid Ave.

department: Genetics & Neurology

institute: Washington University

summary: Alzheimer disease (AD) and Parkinson disease (PD) are the two most common forms of neurodegenerative diseases without effective disease modifying treatments. Despite decades of intensive research, the molecular mechanism of neurodegeneration remains uncertain. We performed the first single-nucleus transcriptome comparison between AD and PD brains.

overall_design: We selected 4 cases with pathological hallmarks of AD, 4 cases diagnosed with PD, and 4 control cases without AD or PD pathology and performed single-nucleus transcriptome comparison using the 10X Genomics platform.

first: Jinbin

last: Xu


title: Chemical genomic screen identifies SP2509, WT hTERT specific repressor in colorectal cancer

status: Public on Dec 01 2022

city: Singapore

first: Raghuvaran

last: Shanmugam

state: Singapore

address: 61 Biopolis Dr, Proteos,

country: Singapore

institute: Institute of Molecular and Cell Biology

summary: Telomerase is necessary for cell immortality in cancer. Hence, during tumerognesis cancer cells reactivates telomerase to attain uncotrolled proliferation. There are no clinically approved drugs available to inhibit telomerase in cancer. We performed a chemical screen using a novel endogenous hTERT reported cell line and identified a compound, SP2509 which acts specifically in cancer cells immortalised by WT TERT activity. Further we identified that Pirin is a molecular target of the compund and it regulate the level of SP1, an important transcriptional activator of WT TERT gene. We finally show iron dependency of pirin to activate TERT in CRC cell lines.

overall_design: HCT116 cells are treated with SP2509 for 48 hrs and/or transiently knockdowned for Pirin using siRNA for 48 hrs. Following the treatment cells, RNA isolation was done using Trizol and DNase treated using M&N RNA mini kit and purified using mini columns


title: Rheumatoid Arthritis macrophages are primed for inflammation and display bioenergetic and functional alterations

city: Dublin 2

first: Megan

middle: Mary

last: Hanlon

state: Dublin

address: Trinity biomedical sciences institute, trinity college dublin

department: School of Medicine

institute: Molecular Rheumatology research group

summary:
To investigate the pro-inflammatory and metabolic function of Rheumatoid Arthritis monocyte derived macrophages
RNA sequencing was perfomed on polarised healthy and Rheumatoid Arthritis monocyte-derived macrophages

overall_design: Comparative gene expression profiling analysis of RNA-seq data for polarised healthy and Rheumatoid Arthritis monocyte-derived macrophages

first: Ursula

last: Fearon


title: A single cell map of murine heart at embryonic and neonatal stages

status: Public on Dec 10 2022

city: Pittsburgh

first: guang

last: li

address: 530 45th St. 8116 Rangos Research Center

institute: university of pittsburgh

summary: Cardiac cells from the wildtype mouse hearts in two strains (CD1, C57BL/6) at 18 developmental stages with chamber separation and two mutant strains (wt1, tbx18) at multiple stages were isolated, multiplexed using the MULTI-seq approach, profiled with the 10X scRNA-seq platform and sequenced with Illumina HiSeq or Nova-seq.

overall_design: ScRNA-seq analysis of wild type and mutant mouse heart cells at multiple stages.

first: Guang

last: Li

first: Wei

last: Feng

first: Abha

last: Bais


title: Microarray gene-expression profiles of 139 pancreatic tumor,102 adjacent non-tumor tissue  from patients with pancreatic ductal adenocarcinoma  and 3 normal pancreas from donors.

first: Hussain

last: Perwez

address: 37 Convent Drive

department: CCR

institute: NIH/NCI

summary: In order to identify key pathways associated with disease aggressiveness and therapeutics resistance in the most agrressive subset of PDAC, we analyzed gene expression profiling of tumor and adjacent non-tumor tissues from PDAC cases. Non-negative matrix factorization (NMF) clustering, using gene expression profile form PDAC tumors, revealed three patient subsets. A 142-gene signature specific to the subset with the worst patient survival, predicted prognosis and stratified patients with significantly different survival. Mechanistic and functional analyses of most aggressive subset revealed a HNF1B/Clusterin Axis negatively regulate pancreatic cancer progression and potentially be useful in designing novel strategies to attenuate disease progression. Affymetrix data from from these dataset were partially earlier submited by us as GEO accession#: GSE28735 and GSE 62452. The batch effect between the different sets of data was removed using Partek Genomic Suite and this normalized data was submitted to GEO in this submission.

overall_design: We selected probes with s.d. >0.6 as the intrinsically variable genes and performed non-negative matrix factorization (NMF) analysis with consensus clustering to identify subsets of the pancreatic adenocarcinoma with cophenetic coefficient > 0.94. This analysis discovered three molecular subsets. Integrative gene expression analysis of these subsets identified a 148 specific gene signature were further submitted to Ingenuity Pathway Analysis (IPA).

first: Shouhui

last: Yang

first: S

last: Perwez Hussain


title: Disease-specific exhaustion features and PD-1 immunotherapy responsiveness of antigen-specific CD8+ T cells at single-cell resolution

status: Public on Nov 29 2022

city: Chicago

first: Jun

last: Huang

state: IL

address: Eckhardt, 5640 S Ellis Ave

department: Institute for Molecular Engineering

institute: University of Chicago

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


title: Domestic dog lineages reveal genetic drivers of behavioral diversification

status: Public on Dec 07 2022

city: Bethesda

first: Alexander

middle: Christian

last: Harris

state: Maryland

address: 50 South Drive

department: National Human Genome Research Institute

institute: National Institutes of Health

type:
SNP genotyping by SNP array
Genome variation profiling by SNP array

summary: Selective breeding of domestic dogs has generated diverse breeds often optimized for performing specialized tasks. Despite the heritability of breed-typical behavioral traits, identification of causal loci has proven challenging due to the complexity of canine population structure. We overcome longstanding difficulties in identifying genetic drivers of canine behavior by developing an innovative framework for understanding relationships between breeds and the behaviors that define them utilizing genetic data for over 4,000 domestic, semi-feral and wild canids and behavioral survey data for over 46,000 dogs. We identify ten major canine genetic lineages and their behavioral correlates and show that breed diversification is predominantly driven by non-coding regulatory variation. We determine that lineage-associated genes converge in neurodevelopmental co-expression networks, identifying a sheepdog-associated enrichment for interrelated axon guidance functions. This work presents a scaffold for canine diversification that positions the domestic dog as an unparalleled system for revealing the genetic origins of behavioral diversity.

sample_organism:
Canis lupus
Canis lupus familiaris
Canis lupus dingo

overall_design: 946 dogs, 9 dingoes, and 1 wolf

first: E

last: Dutrow

first: J

last: Serpell

last: Ostrander


title: The impact of lactate and indole-3-propionate (IPA) on metabolic and epigenetic state of Th17 cells.

status: Public on Nov 25 2022

city: Marburg

first: Wilhelm

last: Bertrams

address: Hans-Meerwein-Str. 2

department: Institute for Lung Research

institute: Philipps University Marburg

summary:
Purpose: Although glycolysis-derived lactate and bacterial product IPA are active metabolites, there is still a lack of understanding of their influence on metabolic and epigentic status of T cells. The aim of this study was to shed light on possible effects of lactate and IPA on function of T cells, including production of cytokines and regulation of trenscriptional factors.
Method: Naive mice (8-12-week-old female mice) were sacrificed and CD4+ T cells were purified from spleens and lymph nodes. T lymphocytes were then treated with lactate or IPA for two days. To ensure that gene signatures were derived from T cells and not from contaminating APCs or B cells, T cell isolation kit from Miltenyi Biotec was used (purity over 95 %).
Results: The analysis of differential expressed genes of lactate- and IPA-treated Th17 cells revealed multiple effects of extracellular lactate and bacterial IPA on the transcriptional profiles. Lactate induced expression of diverse genes associated with transcriptional signature of regulatory T cells.
Conclusion: This study demonstrated that extracellular lactate and microbial metabolite IPA influence transcriptional programs in murine Th17 cells.

overall_design: Purifed CD4+ T cells were differentiated under Th17 conditions for 48 hours in the presence or absence of 25 mM sodium lactate and 50 µM IPA, respectively (n= 3 per group).

first: Aleksandra

last: Lopez Krol

first: Felix

last: Krause

last: Visekruna


title: Disulfiram Plus Nivolumab in Patients with Advanced Gastric Cancer: An Open-Label Phase I Trial

status: Public on Nov 27 2022

city: Chiba

first: Shigeyuki

last: Shichino

address: 2641, Yamasaki, Noda-shi

department: Department of Molecular regulation of Inflammatory and Immune Diseases

country: Japan

institute: Tokyo University of Science

summary: Tumor-associated macrophages correlate with poor prognosis and resistance to immune checkpoint inhibitor therapy in cancer patients. Disulfiram, a drug for alcoholism treatment, has been identified as an inhibitor for FROUNT, which facilitates chemokine-mediated macrophage accumulation to tumor sites. A combination of disulfiram with a PD-1 antibody synergistically inhibits tumor progression in the mouse model. Here, we performed the single-cell transcriptome analysis of gastric cancer specimens before and after treatment with disulfiram plus nivolumab. We explored the immunophenotypical features associated with the response to the treatment.

overall_design: Thirteen patients with gastric cancer were treated with orally administered disulfiram of 160mg 3 times daily for 28 days with intravenous nivolumab 240 mg/body every two weeks with one cycle as four weeks until disease progression or up to six cycles. Specimens were collected once before and after the end of the treatment.

first: Yuya

last: Terashima

first: Hiromichi

last: Nakajima

first: Manami

last: Shimomura

first: Etsuko

last: Toda

first: Hiroyasu

last: Aoki

first: Satoshi

last: Ueha

first: Akinori

last: Sasak

first: Kohei

last: Shitara

first: Tetsuya

last: Nakatsura

first: Kouji

last: Matsushima


title: Single nucleus RNA Sequencing of nontransgenic and Huntington's disease R6/2 mouse striatum and cortex

status: Public on Nov 14 2022

city: Irvine

first: Jie

last: Wu

address: Sprague Hall 332

department: Biological Chemistry

institute: University of California, Irvine

summary: A challenge in treating Huntington's disease (HD) is the complexity of affected brain regions and cell types. We carried out a systematic analysis of cell type-specific changes in cortex and striatum from R6/2 mice at 8 and 12w, and discovered major expression changes in oligodendrocytes (OLs) and oligodendrocyte precursors (OPCs), suggesting that many OLs were arrested in an immature state. Causal gene network analysis implicates PRKCE and SWI/SNF in abnormal OL maturation. PRKCE protein was dramatically decreased. Disrupted cell-to-cell signaling between medium spinyneurons and OL that may contribute to neuronal dysfunction was identified in R6/2 mice using ligand-receptor analysis. These findings reveal novel insights into OL pathology, span multiple brain regions in humans and mice and suggest therapeutic strategies.

overall_design: Single Nucleus RNA-Seq of NT and R62 mouse striatum and cortex. snucRNAseq profiles of NT and R6/2 striatum and cortex were generated with the 10x genomics platform and sequenced using the Illumina Hiseq 4000.

first: Ryan

last: Lim

first: Leslie

middle: M

last: Thompson


title: Spatial transcriptomics landscape of non-communicable inflammatory skin diseases

city: Munich

first: Christina

last: Hillig

address: Ingolstaedter Landstraße 1

department: ICB

institute: Helmholtz Center Munich

summary: We investigated the landscape of non-communicable inflammatory skin diseases by spatial transcriptomics resulting in a large repository of spatially defined human cutaneous transcriptomes of 31 patients.

overall_design: Dataset containing 90 spatial transcriptomic sequencing samples of skin biopsies taken from 31 patients diagnosed with psoriasis, atopic dermatitis or lichen planus, including duplicates of 31 lesional and 14 matched non-lesional samples. Samples  21L008958-21L008973 contain 2-3 specimen on a capture area from different patients and diseases.

first: Alexander

last: Schaebitz

first: Menatullah

last: Mubarak

first: Manja

last: Jargosch

first: Ali

last: Farnoud

first: E.

last: Scala

first: Nils

last: Kurzen

last: Pilz

first: N.

last: Bhalla

first: J.

last: Thomas

first: M.

last: Stahle

first: T.

last: Biedermann

last: Schmidt-Weber

first: Fabian

last: Theis

first: Thomas

last: Walzthoeni

first: Natalie

last: Garzorz-Stark

first: Kilian

last: Eyerich

first: Michael

last: Menden

first: Stefanie


title: Transcriptomic landscape of adult de novo acute myeloid leukemia offers prognostic biomarkers and putative targets

status: Public on Nov 23 2022

city: SHANGHAI

first: Peng

last: Jin

state: SHANGHAI

address: No.197 RUIJIN ER RD

institute: SHANGH RUIJIN HOSPITAL

summary: Acute myeloid leukemia (AML), caused by an interplay of genetic and epigenetic alterations, is a heterogeneous hematological malignancy characterized by accumulation of proliferative clonal abnormally myeloblasts in the bone marrow and blood. Chemotherapy resistance is common, and relapses occur frequently for the majority of AML patients, indicating a strong need for better therapeutic strategies. The molecular complexity of acute myeloid leukemia (AML) presents a considerable challenge to implementation of clinical genetic testing for accurate risk stratification. Identification of better biomarkers and alternative targeted therapeutic strategies therefore remain a high priority to enable improving established stratification and guiding risk-adapted therapy decisions. RNA-sequencing offers the greatest diagnostic return, enabling identification of whole-transcriptome expression, expressed gene fusions, single nucleotide and short insertion/deletion variants, and alternative splicing information. Therefore, a total of 157 patient bone marrow samples were collected as diagnosis and subjected to RNA-seq.

overall_design:
A total of 157 AML patients (age 18-74years; 54.8% males, 45.2% females) were included. Comprehensive gene expression profiling analysis was then performed.
---------------------------------
Authors state "Law restrictions prohibit us from publicly sharing raw sequencing data, which however can be made available upon reasonable request and permission of the local ethics committee."

first: J

last: Li

first: X

first: M

last: Zhao

first: P


title: Identification of aceNKPs, a committed common progenitor of the ILC1 and NK cell continuum

status: Public on Nov 02 2022

city: Cambridge

first: Alastair

last: Crisp

address: Francis Crick Avenue

institute: MRC Laboratory of Molecular Biology

summary: The development of innate lymphoid cell (ILC) transcription factor reporter mice has shown a previously unexpected complexity in ILC haematopoiesis.  Using novel polychromic mice to achieve higher phenotypic resolution we have characterised bone marrow progenitors that are committed to the group 1 ILC lineage.  These common ILC1/NK progenitors, which we call ‘aceNKPs’, are defined as lineage–Id2+IL-7Ra+CD25–a4b7–NKG2A/C/E+Bcl11b–.  In vitro, aceNKPs differentiate into group 1 ILCs, including NK-like cells that express Eomes without the requirement for IL-15, and produce IFN-g and perforin upon IL-15 stimulation.  Following reconstitution of Rag2–/–Il2rg–/– hosts, aceNKPs give rise to a spectrum of mature ILC1/NK cells (regardless of their tissue location) that cannot be clearly segregated into the traditional ILC1 and NK subsets, suggesting that group 1 ILCs constitute a dynamic continuum of ILCs that can develop from a common progenitor.  In addition, aceNKP-derived ILC1/NK cells effectively ameliorate tumour burden in a model of lung metastasis where they acquired a cytotoxic NK cell phenotype. Our results identify the primary ILC1/NK progenitor that lacks ILC2 or ILC3 potential and is strictly committed to ILC1/NK cell production irrespective of tissue homing.

overall_design: Mouse aceNKPs from the bone marrow cells were purified by flow cytometry into heat-inactivated FCS, diluted to 50% with PBS and washed with PBS before injection.  Cell suspensions were aspirated with a syringe, resuspended in endotoxin-free sterile PBS to a concentration of 1000 aceNKPs/mL, and implanted via tail vein injection into sublethally-irradiated (450 rad) CD45.1 Rag2–/–Il2rg–/– recipients (100-200 cells per mouse).  Analysis of donor cell progeny was performed 7 weeks after cell transfer.  Lungs were harvested and pre-digested by finely chopping the tissue and incubating it with 750 U/mL collagenase I (GIBCO) and 0.3 mg/mL DNaseI (Sigma-Aldrich) prior to obtaining a single cell suspension by straining the tissue through a 70mm cell strainer.  After washing, blood cells were removed by incubation with RBC lysis solution (140 mM NH4Cl, 17 mM Tris; pH 7.2).  Lung lymphocytes were further enriched by centrifugation in 30% Percoll at 850 x g for 10 min (GE Healthcare), followed by a final wash with PBS with 3% FCS. Samples were stained with anti-CD45.1, Life/Dead fixable dye eF780, anti NK1.1.  aceNKP-derived progeny was isolated by flow cytometry as Live CD45.2+Id2+, pelleted and submitted  for 10x Chromium single cell RNA sequencing.  Single-cell library preparation was performed using the 10x Genomics technology, and the 3′ libraries were obtained through the 10x Genomics Chromium Single-Cell 3′ v3 protocol and underwent subsequent sequencing.  The reads were aligned to the mouse transcriptome (GRCm38), and expression and clusters were determined using 10x Genomics Cell Ranger (version 6.0.1).  Further analysis and statistical calculations were performed using the 10x Genomics Loupe Browser (version 5.1) (https://support.10xgenomics.com/single-cell-gene-expression/software/visualization/latest/what-is-loupe-cell-browser).  Data outliers such as contaminating myeloid cells and dead cells were removed from the analysis by applying the following parameters: UMI threshold: 500-20000; genes per barcode > 500; mitochondrial UMI < 5%; Ptprc expression > 0.1; Sirpa, Cd63, Csf1r, Csf2ra, Trpm2, Clec9a expression < 0.002.

first: Noe

last: Rodriguez-Rodriguez

first: Paula

last: Clark

first: Mayuri

last: Gogoi

first: Ana

middle: C

last: Ferreira

first: Bernhard

last: Kerscher

first: Helen

last: Jolin

first: Jane

last: Murphy

first: Meera

last: Sivasubramaniam

first: Luisa

last: Pedro

first: Jennifer

last: Walker

first: Morgan

last: Heycock

first: Jacqueline

middle: D

last: Shields

first: Jillian

middle: L

last: Barlow

first: Andrew

middle: N

last: McKenzie


title: RNA-sequencing

status: Public on Oct 25 2022

city: changchun

first: yongwei

last: su

address: 2699 qianjin street

institute: Jilin university

summary: RNA-sequencing for 10 samples

overall_design: Examing 2 conditions, each with five cells


title: Role of CEP112 and hnRNPA2B1 complex phase separation in RNA granule translation during spermiogenesis in humans and mice

status: Public on Nov 05 2022

city: chengdu

first: li

last: tongtong

state: sichuan

address: sichuan

institute: xinong

summary:
Centrosomal proteins (CEPs) are active components of centrioles that mediate multiple biological processes, such as ciliogenesis and centriole biogenesis; therefore, CEP dysfunctions are broadly implicated in various human diseases. Although CEPs have been genetically linked to reproduction, the underlying molecular mechanisms remain poorly understood. Here, we report that knocking out Cep112 in mice causes male infertility with various sperm abnormalities and phenotypes consistent with human asthenoteratozoospermia. Microscopic observations revealed CEP112 is a novel component of atypical centrioles in human sperm cells. Mechanically, as an intrinsically disordered region-rich RNA-binding protein, CEP112 interacted with hnRNPA2B1 and condensed with key spermiogenesis-related mRNA molecules (Fsip2, Cfap61, and Cfap74) via liquid–liquid phase separation, which promoted RNA transport and the maintenance of local translation during spermiogenesis. Furthermore, two patients with bi-allelic variants in CEP112 were identified in a cohort of 568 unrelated infertile men, and in vitro experiments showed the mutations affected the phase-separation characteristics. Our findings provide new information on the roles of CEP112 and LLPS in male reproductive biology.
4 samples

overall_design: Wenming,Xu

first: Xueguang

last: Zhang

first: Tongtong

last: Li


title: Transcriptomic profiling of drug-treated human induced pluripotent stem cells (iPSCs) [Conv-GEO-Depot]

city: New York

first: Ravi

last: Iyengar

state: NY

address: 1425 Madison Avenue, Room 12-70C

department: Pharmacological Sciences

institute: Icahn School of Medicine at Mount Sinai

summary: Kinase inhibitors (KIs) are a promising alternative to traditional chemotherapeutics in the treatment of multiple cancer types. Unfortunately, some kinase inhibitors induce cardiotoxicity as a severe side effect. To identify gene expression signatures that might be indicative of kinase inhibitor-induced cardiotoxicity, we generated six cardiomyocyte cell lines from induced pluripotent stem cells that we obtained from six healthy volunteers. Treatment of these cell lines with 54 FDA-approved drugs, i.e. 23 kinase inhibitors, 4 monoclonal antibodies, 4 anthracyclines, 7 cardiac acting and 16 non-cardiac acting drugs, allowed generation of 266 lists of differentially expressed genes. We subjected those lists to unsupervised and supervised algorithms to identify differentially expressed pathway activities associated with cardiotoxic responses.

overall_design: Six different iPSC-derived cardiomyocyte cell lines were treated with one out of 54 FDA-approaved drugs or DMSP for 48 hours, followed by bulk RNAseq analysis. Differentially expressed genes were identified between drug- and control treated cell lines.

first: Jens

last: Hansen

first: Yuguang

last: Xiong

first: Priyanka

last: Dhanan

first: Bin

last: Hu

first: Gomathi

last: Jayaraman

first: Rosa

last: Tolentino

first: Yibang

last: Chen

first: Kristin

middle: G

last: Beaumont

first: Robert

last: Sebra

first: Dusica

last: Vidovic

first: Stephan

last: Schürer

first: Joseph

last: Goldfarb

last: Gallo

first: Marc

last: Birtwistle

first: Eric

last: Sobie

first: Evren

middle: U

last: Azeloglu

first: Seth

last: Berger

first: Angel

last: Chan

first: Christoph

last: Schanie

first: Nicole

last: Dubois


title: scRNAseq analysis of lytically and latently infected KSHV-infected iSLK.219 cells with and without caspase inhibitor treatment

status: Public on Sep 29 2022

city: Madison

first: Marta

middle: Maria

last: Gaglia

state: WI

address: 1525 Linden Dr

institute: University of Wisconsin Madison

summary: The goal of this analysis was to examine the cell-to-cell variation in Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation and type I interferon response after caspase inhibitor treatment. We profiled the levels of host and viral mRNAs at a single-cell level using the iSLK.219 tissue culture model system (Myoung and Ganem, 2011). We examined gene expression in lytically reactivating cells, lytically reactivating cells treated with caspase inhibitors, and lytically reactivating cells treated with casapse inhibitors and neutralizing antibodies against interferons. (we previously described that caspase inhibitors elicit an interferion response in KSHV-infected cells, Tabtieng et al., 2018). We also examined gene expression in a mixture of latently infected cells and uninfected cells as a control.

overall_design: iSLK.219 cells were treated with doxycyline to induce lytic reactivation (as per Myoung and Ganem, 2011) or left untreated for latently infected cells. The doxycycline induces expression of an exogenous copy of the KSHV lytic regulator RTA. For caspase inhibitor treated samples, they were treated with the pan-caspase inhibitor IDN-6556 and for anti-inteferon antibody treatment, they were treated with a mixture of monoclonal and polyclonal antibodies directed against human type I Interferons and type I Interferon Receptor Subunit 2 (IFNAR2). Untreated samples received vehicle. All drugs were replenished two days after the start of reactivation and treatment, and samples for scRNAseq were collected 4 days after the start of treatment. Uninfected iSLK.H cells were mixed with vehicle-treated uninduced iSLK.219 cells before single-cell analysis. The 10x Genomics platform was used to measure single-cell RNA levels.

first: Tate

last: Tabtieng


title: Distinct immunological and molecular signatures predict influenza vaccine responsiveness in the elderly

city: Braunschweig

last: Geffers

address: Inhoffenstr. 7

department: Dep. Molecular Bacteriology

institute: HCI - Helmholtz Centre for Infection Research

summary: The significant economic burden and high mortality rates resulting from seasonal influenza outbreaks, especially in high risk groups such as the elderly, represent an important public health problem. The prevailing inadequate efficacy of seasonal vaccines, both conventional and elderly-tailored, is a crucial bottleneck. Consequentially, understanding immunological and molecular mechanisms resulting in differential influenza vaccine responsiveness is a prerequisite for the development of new or improved vaccination strategies. To assess differences within the specific risk group of the elderly, randomly selected individuals (≥ 65  years) were immunized with the adjuvanted influenza vaccine Fluad®. Samples were subjected to transcriptome analysis. The analyses revealed profound features segregating vaccine responders from nonresponders  as classified according to their vaccine-induced sero-conversion. Non-responders are characterized by a poorly functional, suppressive phenotype, showing a weaker humoral and cellular immune activation and more suppressive regulatory T and B cells. Triple responders display an efficient immune functionality characterized by the activation of humoral and cellular immunity and the up-regulation of genes related to signaling pathways, including those for anti-viral responses, protein processing and B cell activation. The generated comprehensive high dimensional dataset enables the identification of putative mechanisms and nodes responsible for vaccine non-responsiveness regardless of confounding age-dependent effects.

overall_design: For the bulk transcriptome analysis, PBMCs isolated from whole blood samples ( 10 responders (TR)/ 10 non-responders (TNR)) taken at five time points (V1-V5)  were used. V1= before vaccination, V2=1/3 days after Vac., V3= 7 days after Vac., V4=21 days after Vac., V5= 70 days after Vac

first: Peggy

last: Riese

first: Stephanie

last: Trittel

first: Carlos

middle: A

last: Guzmán


title: Retrotransposon addiction promotes centromere function via epigenetically activated small RNAs

status: Public on Oct 24 2022

city: Cold Spring Harbor

last: Martienssen

address: 1 Bungtown Rd

department: Delbruck Bldg.

institute: Cold Spring Harbor Laboratory

type: Methylation profiling by high throughput sequencing

summary: Retrotransposons have invaded eukaryotic centromeres in cycles of repeat expansion and purging, but the function of centromeric retrotransposons, if any, has remained unclear. In Arabidopsis, centromeric ATHILA retrotransposons give rise to epigenetically activated short interfering RNAs (easiRNAs) in mutants in DECREASE IN DNA METHYLATION1 (DDM1), which promote histone H3 lysine-9 di-methylation (H3K9me2). Here, we show that mutants which lose both DDM1 and RNA dependent RNA polymerase (RdRP) have pleiotropic developmental defects and mis-segregation of chromosome 5 during mitosis. Fertility defects are epigenetically inherited with the centromeric region of chromosome 5, and can be rescued by directing artificial small RNAs to a single family of ATHILA5 retrotransposons specifically embedded within this centromeric region. easiRNAs and H3K9me2 promote pericentromeric condensation, chromosome cohesion and proper chromosome segregation in mitosis. Insertion of ATHILA silences transcription, while simultaneously making centromere function dependent on retrotransposon small RNAs, promoting the selfish survival and spread of centromeric retrotransposons. Parallels are made with the fission yeast S. pombe, where chromosome segregation depends on RNAi, and with humans, where chromosome segregation depends on both RNAi and HELLSDDM1.

overall_design: Whole genome bisulfite sequencing of ddm1 epigenetic recombinant lines in rdr1 rdr2 rdr6; Whole genome sequencing and whole genome bisulfite sequencing of rdr1 rdr2 rdr6 ddm1 suppressors; H3K9Me2 ChIP-seq in wild-type, rdr1 rdr2, rdr1 rdr2 rdr6, rdr1 rdr2 ddm1, rdr1 rdr2 rdr6 ddm1, rdr1 rdr2 rdr6 ddm1 ATHILA5-hp suppressor; CenH3 ChIP-seq in wild-type, rdr1 rdr2 rdr6, rdr1 rdr2 ddm1, rdr1 rdr2 rdr6 ddm1, rdr1 rdr2 rdr6 ddm1 ATHILA5-hp suppressor and rdr1 rdr3 rdr6 ddm1 episuppressor 3-75; ONT direct methylation sequencing of rdr1 rdr2 rdr6 ddm1 and rdr1 rdr2 rdr6 ddm1 ATHILA5-hp suppressor.

first: Atsushi

last: Shimada

first: Jonathan

last: Cahn

first: Evan

last: Ernst

first: Jason

last: Lynn

first: Daniel

last: Grimanelli

first: Ian

last: Henderson

first: Tetsuji

last: Kakutani


title: Activation of a singlet oxygen signaling pathway by competition cues in Arabidopsis thaliana

status: Public on Sep 14 2022

city: Guelph

first: Clarence

last: Swanton

state: Ontario

address: 50 Stone Rd. East

department: Plant Agriculture

institute: University of Guelph, Department of Plant Agriculture

summary:
The goal of this work was to investigate oxidative stress responses of Arabidopsis to low red to far-red ratios of light as a signal of competition using a biological weedy and an artificial source of far-red light. More specifically, elucidation of the signaling role of singlet oxygen in Arabidopsis under low red-to far-red light environments was the major objective of this work.
Oxidative stress responses of Arabidopsis to low red (R) to far-red (FR) signals (R:FR ≈ 0.3), generated by a biological weedy and an artificial source of FR light, were compared with a weed-free control (R:FR ≈1.4). In the low R:FR treatments, induction of the shade avoidance responses coincided with increased singlet oxygen (1O2) production and decreased level of superoxide and superoxide dismutase activity. Although the increase of 1O2 was not due to protochlorophyllide accumulation and did not result in cell death, treatments with the 1O2 generator 5-aminolevulinic acid increased sensitivity to cell death. Transcriptome responses minimally resembled those reported in four Arabidopsis 1O2 generating systems such that only few genes (6 out of 1931) were consistently up-regulated supporting the specificity of 1O2 signaling. Moreover, suppressors of jasmonate accumulation, including the 1O2-responsive amidohydrolase ILL6, the sulfotransferase ST2a, which are involved in prioritization of elongation growth versus defense were consistently up-regulated. Our data support a model in which photoreceptors connect low R:FR light cues to the JA signaling pathway. Repression of bioactive JAs via the amidohydrolase ILL6, and sulfotransferase ST2a may promote the shade avoidance (versus defense) and 1O2 acclimation (versus cell death) responses to competition cues.

overall_design: Total RNA was extracted from 4-week-old rosette leaves of wild type Arabidopsis thaliana (ecotype Columbia). In total, 9 samples consisting of 3 treatments with 3 replicates, each consisting of a pool of leaves from 3 individual plants, were analyzed. The 3 treatments consisted of a weed-free control (high red to far-red light ratio), a biological low red to far-red light ratio using a surrogate weed, and an artificial low red to far-red light ratio using far-red LEDs. The red to far-red ratios (R:FR) at the plant level was approximately 1.4, 0.3 and 0.3 in the control, biological low R:FR, and artificial low R:FR treatments, respectively. In all treatments, plastic tubes were placed in the center of the experimental pots and plastic cups containing the Arabidopsis plants were inserted in the central tubes. This experimental set up prevented direct root contact between the surrogate weed and Arabidopsis plants. In the control treatment, Arabidopsis plants were grown at an R:FR ≈ 1.4 for 4 weeks, whereas plants in the biological and artificial low R:FR treatments were grown at an R:FR ≈ 1.4 for 3 weeks and transferred to the respective low R:FR light treatments (R:FR ≈ 0.3) for 1 week.

last: Berardi

first: Sasan

last: Amirsadeghi


title: Cdk8 attenuates lipogenesis by inhibiting SREBP-dependent transcription in Drosophila

status: Public on Nov 09 2022

city: New Orleans

first: Jun-yuan

last: Ji

state: LA

address: 1700 Tulane Avenue

department: Department of Biochemistry and Molecular Biology

institute: Tulane University

summary: Fine-tuning of lipogenic gene expression is important for the maintenance of long-term homeostasis of intracellular lipids. The SREBP family of transcription factors are master regulators that control the transcription of lipogenic and cholesterogenic genes, but the mechanisms modulating SREBP-dependent transcription are still not fully understood. We previously reported that CDK8, a subunit of the transcription co-factor Mediator complex, phosphorylates SREBP at a conserved threonine residue. Here, using Drosophila as a model system, we observed that the phosphodeficient SREBP proteins (SREBP-Thr390Ala) were more stable and more potent in stimulating the expression of lipogenic genes and promoting lipogenesis in vivo than wild-type SREBP. In addition, starvation blocked the effects of wild-type SREBP-induced lipogenic gene transcription, whereas phosphodeficient SREBP was resistant to this effect. Furthermore, our biochemical analyses identified six highly conserved amino acid residues in the N-terminus disordered region of SREBP that are required for its interactions with both Cdk8 and the MED15 subunit of the small Mediator complex. These results support that the concerted actions of Cdk8 and MED15 are essential for the tight regulation of SREBP-dependent transcription.

overall_design: RNA-seq for differential expressed genes comparing CDK8K185 mutant to w1118 (control) larvae

first: Xiao

last: Li

first: Meng

last: Zhang

first: Mengmeng

last: Liu

first: Tzu-Hao

first: Rajitha-Udakara-Sampath

last: Hemba-Waduge

first: Jun-Yuan


title: Global identification of circRNAs in chronic myeloid leukemia reveals a circRNA signature associated with the disease progression

status: Public on Sep 05 2022

city: Wenzhou

first: Zhanguo

last: Chen

state: Zhejiang

address: 109 Xueyuan Xi Road, Wenzhou, Zhejiang 325000, P.R. China

department: Department of Clinical Laboratory

institute: The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University

type: Non-coding RNA profiling by high throughput sequencing

summary:
The circRNAs of chronic myelelogenous leukemia (CML) accelerated phase and chronic phase (CP) were more obvious than normal subjects.   QRT-PCR verified that the expressions of hsa_circ_0001523, hsa_circ_0006010 and hsa_circ_0066971 were significantly up-regulated, while the expressions of hsa_circ_000095, hsa_circ_0001801 and HSA_circ_0002903 were down-regulated in advanced patients.   Bioinformatics analysis revealed that some dysregulated crRnas may be active in important biological pathways by acting as miRNA sponges during CML disease progression.
These six circrnas have high diagnostic value.   Our study confirms significant circrNA dysregulation in CML patients and describes a circrNA marker associated with CML disease progression.

overall_design: CircRNAs expression profiles were analyzed by high-throughput RNA sequencing (RNA-seq). Candidate circRNAs were confirmed by quantitative real-time PCR (qRT-PCR). Bioinformatics analysis predicted the potential functions of these circRNAs. Receiver operating characteristic curve (ROC) analysis, Spearman’s rho correlation test and Chi-square test were used.

first: Guiran

last: Wang

first: Guiling

last: Yan


title: Single-cell RNA-seq of brassinosteroid response in Arabidopsis roots

city: Durham

first: Philip

middle: N.

last: Benfey

state: North Carolina

address: 130 Science Drive

department: Biology

institute: Duke University

summary: We report both raw and processed scRNA-seq data profiling brassinosteroid response and related mutants in Arabidopsis roots

overall_design: scRNA-seq of 4 wild-type and 20 brassinosteroids-related mutants or treatments. The supplemtary file (BR_time_course.rds.gz) contains WT sample (sc_1) from our previously published work (GSE152766, Sample GSM4625993).

first: Trevor

last: Nolan

first: Nemanja

last: Vukašinović

first: Che-Wei

last: Hsu

first: Jingyuan

first: Isabelle

last: Vanhoutte

first: Rachel

last: Shahan

first: Isaiah

middle: W

last: Taylor

first: Laura

last: Greenstreet

first: Matthieu

last: Heitz

first: Ping

first: Pablo

last: Szekely

first: Aiden

last: Brosnan

first: Heather

last: Belcher

first: Anton

last: Afanassiev

first: Yanhai

last: Yin

first: Geoffrey

last: Schiebinger

first: Uwe

last: Ohler

first: Eugenia

last: Russinova


title: Transcriptional changes upon Mphosph8 or Morc2a loss

status: Public on Sep 13 2022

city: Vienna

first: Maria

last: Novatchkova

address: Dr Bohrgasse

institute: IMP/IMBA

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

overall_design: Refer to individual Series


title: Donor-cell memory confers metastable state of directly converted cells

city: Muenster

first: Hyun-Woo

last: Jeong

state: NRW

department: Dept. Tissue Morphogenesis

institute: Max-Planck-Institute for Molecular Biomedicine

summary: How the phenotypic instability of directly converted cells influences in vivo functional consequences is largely unknown. Here we show that the directly converted iOPCs exhibit a metastable state, such that they can progress to mature oligodendrocytes or revert back to the donor-cell type in a context-dependent fashion. Thus, therapeutic use of such cells will require a more detailed understanding of mechanisms by which the fate of directly converted cells may be rendered durable.

overall_design: Direct conversion of MEFs and PCs into iOPCs by ectopic expression of Olig2, Sox10 and Nkx6.2

first: Kee-Pyo

last: Kim

first: Hans

middle: R

last: Schöler

first: Ralf

middle: H

last: Adams


title: Targeting epithelial-mesenchymal plasticity via ribosome inhibition to reduce chemoresistant metastasis of breast cancer

status: Public on Sep 01 2022

first: Dingcheng

last: Gao

address: 1300 York Ave

department: CT Surgery

institute: Weill Cornell Medical College


title: Spatial RNA sequencing of mouses brain slices following spatial object recognition training

status: Public on Nov 01 2022

city: Iowa City

first: Ethan

last: Bahl

state: IA

address: 25 S Grand Ave

institute: University of Iowa

summary: We report a spatial transcriptomics dataset of mouse brain tissue generated with the 10x Genomics Visium platform to identify gene expression profiles of spatial object recognition training.

overall_design: We performed spatial gene expression profiling analysis using Visium data obtained from coronal mouse brain sections of 2 groups (trained vs. home cage).

first: Snehajyoti

last: Chatterjee

first: Muhammad

last: Elsadany

first: Yann

last: Vanrobaeys

first: Li-Chun

last: Lin

first: Peter

last: Giese

first: Ted

last: Abel

first: Jacob

middle: J

last: Michaelson


title: Targeting epithelial-mesenchymal plasticity via ribosome inhibition to reduce chemoresistant metastasis of breast cancer [bulk RNA-seq]

summary: Using an EMT lineage-tracing model, we identified tumor cells in the transitioning phases of both EMT and MET. Further analyses revealed that the ribosome biogenesis (RiBi) pathway was specifically elevated in these transitioning cells, regardless of their destined phenotypical fates.

overall_design: mRNA profiling of flow cytometry sorted RFP+, GFP+, and Double+ Tri-PyMT cells. 3 samples of each type of cells were sequenced.

first: Yi

last: Ban


title: Transcriptomic profiling of drug-treated human induced pluripotent stem cells (iPSCs)

first: Ravi

last: Iyengar