title: Comparative analysis of innate immune responses to viral infection among animals

city: Minato-ku

first: Kei

last: Sato

state: Tokyo

address: 4-6-1 Shiroganedai

department: Department of Microbiology and Immunology

country: Japan

institute: The Institute of Medical Science, The University of Tokyo

summary: Bats harbour various viruses without severe symptoms and act as natural reservoirs. This tolerance of bats toward viral infections is assumed to be originated from the uniqueness of their immune system. However, how the innate immune response varies between primates and bats remains unclear. To illuminate differences in innate immune responses among animal species, we performed a comparative single-cell RNA-sequencing analysis on peripheral blood mononuclear cells (PBMCs) from four species including Egyptian fruit bats inoculated with various infectious stimuli.

sample_organism:
Rousettus aegyptiacus
Macaca mulatta
Pan troglodytes
Homo sapiens

overall_design: PBMCs were obtained from human (Homo sapiens), chimpanzee (Pan troglodytes), rhesus macaque (Macaca mulatta), and Egyptian fruit bat (Rousettus aegyptiacus). PBMCs were treated with herpes simplex virus type 1 (HSV-1) (strain F; GenBank accession number: GU734771), Sendai virus (SeV) (strain Cantrell, clone cCdi; GenBank accession number: AB855654) or lipopolysaccharide (LPS). On one day post infection, these infected/stimulated PBMCs (HSV-1, SeV, and LPS) were collected. Unstimulated PBMCs (Mock) were also prepared. A total of 16 samples (4 species × 4 stimuli) were loaded into the Next GEM chip G using a Chromium controller. Reverse transcription were performed in each GEM and barcoded cDNA were produced. After cDNA amplification, enzymatic fragmentation end repair, A-tailing, adaptor ligation and index PCR were processed.

first: Hirofumi

last: Aso

first: Jumpei

last: Ito

first: Yukie

last: Kashima

first: Yutaka

last: Suzuki

first: Haruka

last: Ozaki

first: Yoshio

last: Koyanagi


title: Genome-wide enhancer-gene regulatory maps link causal variants to target genes underlying human colorectal cancer risk [ATAC-seq]

status: Public on Jan 17 2023

city: Wuhan

first: Can

last: Chen

state: Hubei

address: Donghu Road

department: Department of Epidemiology and Biostatistics, School of Public Health

country: China

institute: Wuhan University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Although GWASs have identified thousands of variants associated with human complex traits, most of which reside in the non-coding regions, especially enhancers, and biological mechanisms remain unclear. To created enhancer-gene maps to determine causal variant of CRC risk, we performed multi-omics analyses of ATAC-seq, H3K27ac ChIP-seq and RNA-seq with high quality from our 10 CRC tissues. By computationally integrating these multi-omics data, we identified 34,130 enhancer-gene connections involving 15,121 unique enhancers and 12,351 expressed genes. We demonstrated an ABC regulatory variant rs4810856 that is significantly associated with an increased CRC risk with large-scale population study and biological experiments. Our study provides regulation maps linking enhancers to genes, providing new insights into colorectal cancer etiology.

overall_design: bulk ATAC-seq was performed on 10 colorectal cancer samples from CRC patients

first: Zequn

last: Lu


title: Genome-wide enhancer-gene regulatory maps link causal variants to target genes underlying human colorectal cancer risk [H3K27ac ChIP-seq]

summary: Although GWASs have identified thousands of variants associated with human complex traits, most of which reside in the non-coding regions, especially enhancers, and biological mechanisms remain unclear. To created enhancer-gene maps to determine causal variant of CRC risk, we performed multi-omics analyses of ATAC-seq, H3K27ac ChIP-seq and RNA-seq with high quality from our 10 CRC tissues.

overall_design: 10 CRC samples without treatment were acquired for H3K27ac CHIP-seq


title: Loss of DKC1 facilitates the acquisition of metastatic traits by altering cholesterol metabolism via the mevalonate pathway

city: Barcelona

first: Júlia

last: Perera-Bel

address: Doctor Aiguader, 88

department: MARData-BU

country: Spain

institute: Hospital del Mar Research Institute

type:
Non-coding RNA profiling by array
Expression profiling by array

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

platform_organism:
Homo sapiens
synthetic construct

overall_design: Refer to individual Series


summary:
Analysis of sncRNA expression in 22 primary cSCC (10 from cSCCs that had evolved to histologically confirmed metastases, or MSCC, and 12 from a cSCC control group who had not developed any metastasis in a 5-year follow-up period).
Unsupervised hierarchical clustering of the most variably expressed sncRNAs stratified the tumors into two groups, one formed mainly by NMSCC and the other formed exclusively by metastasizing cSCC, the latter displaying an overall sncRNA downregulation. Supervised clustering of MSCC vs. NMSCC identified the differential expression of 330 sncRNAs, most of them downregulated in the metastasizing group (248 sncRNAs; 75%). Functional and sequence-based classification of the probes in the array revealed alterations in the proportion of the snoRNAs represented in MSCCs when compared to their expression in NMSCCs.

overall_design: 22 samples were analysed (CTRL=12,SCC=10)

first: Agustí

last: Toll

first: Inmaculada

last: Hernández-Muñoz


title: Genome-wide enhancer-gene regulatory maps link causal variants to target genes underlying human colorectal cancer risk [RNA-seq]

type: Expression profiling by high throughput sequencing

overall_design: Comparative gene expression profiling analysis of RNA-seq data was performed on 10 colorectal cancer samples from CRC patients


title: Gene expression analysis of C. elegans L1 larvae fed with wild-type Pseudomonas aeruginosa CF18 and P. aeruginosa CF18 gacA mutant

status: Public on Jan 15 2023

city: Worcester

first: Zeynep

last: Mirza

state: MA

address: 373 Plantation Street

department: Molecular Medicine

country: USA

institute: University of Massachusetts Chan Medical School

summary: To determine the genes that are differentially expressed in CF18-fed larvae and CF18 gacA-fed larvae, we performed RNA-sequencing (RNA-seq) after 4 hours and 6 hours of bacterial exposure.

overall_design: Larvae fed CF18 and CF18 gacA mutant were collected after 4 and 6 hours. Three biological replicates were performed for each bacterial diet and time point.

first: Alberta J.

middle: M

last: Walhout

first: Victor

last: Ambros


title: Gene expression analysis of  Pseudomonas aeruginosa strain CF18 and P. aeruginosa CF18 gacA mutant

summary: We compared gene expression in wild-type P. aeruginosa strain CF18 relative to P. aeruginosa CF18 gacA mutant.

overall_design: P. aeruginosa CF18 and P. aeruginosa CF18 gacA mutant were seeded on slow-killing plates. The plates were incubated for 24 h at 37ºC and then for 24 h at 25ºC. °C. Then, bacteria were collected from the plates and total RNAs were extracted (Three biological replicates for WT CF18 and 2 biological replicates for gacA mutant).

first: Alberta

middle: J


title: The impact of gut microbiome on transcriptome in Parkinson's disease model revealed by fecal microbiota transplantation

status: Public on Jan 13 2023

city: Guangzhou

first: Xiaoyun

last: Wang

state: Guangdong

address: 190 Kaiyuan Avenue, Huangpu

department: Infection and Immunity

institute: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences

summary: Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. The disorder of gut microbiota is involved in the pathophysiological process of various neurological diseases, and many studies have confirmed that gut microbiota is involved in the progression of PD. As one of the most effective methods to reconstruct gut microbiota, fecal microbiota transplantation (FMT) has been considered as an important treatment for PD. However, the mechanism of FMT treatment for PD is still lacking, which requires further exploration and can facilitate the application of FMT. As a model organism, Drosophila is highly conserved with mammalian system in maintaining intestinal homeostasis. In this study, there were significant differences in the gut microbiota of conventional Drosophila colonized from PD patients compared to those transplanted from normal controls. And we constructed rotenone-induced PD model in Drosophila followed by FMT in different groups, and investigated the impact of gut microbiome on transcriptome of the PD host. Microbial analysis by 16S rDNA sequencing showed that gut microbiota could affect bacterial structure of PD, which was confirmed by bacterial colonization results. In addition, transcriptome data suggested that gut microbiota can influence gene expression pattern of PD. Further experimental validations confirmed that lysosome and neuroactive ligand-receptor interaction are the most significantly influenced functional pathways by PD-derived gut microbiota. In summary, our data reveals the influence of PD-derived gut microbiota on host transcriptome and helps better understanding the interaction between gut microbiota and PD through gut-brain axis. The present study will facilitate the understanding of the mechanism underlying PD treatment with FMT in clinical practice.

overall_design: To dissect the relationship between gut microbiota and PD, we first constructed PD model by inducing Drosophila melanogaster with rotenone for 7 days. PD models were validated through phenotypic observation and molecular testing, we then performed cross-colonization experiments (Figure 1A). The PD flies and control flies were subjected with/o FMT for another 7 days. After cross-colonization experiments, we obtained six different groups of flies including control Drosophila (CTRL), Parkinson's Drosophila (PD), control Drosophila with FMT from Parkinson's Drosophila (CWFP), control Drosophila without FMT from Parkinson's Drosophila (CWOFP), Parkinson's Drosophila with FMT from control Drosophila (PWFC) and Parkinson's Drosophila without FMT from control Drosophila (PWOFC).

first: Xin

last: Liu

first: Meng

last: Yang

first: Haibing

last: Zhu


title: DKC1 downregulation by transient transfection of UT-SCC12A cells with siDKC1

summary: We have investigated the functional effects of DKC1 downregulation in cSCC cells, and unveiled new roles for DKC1 in the metastatic process: metabolism and invasiveness. Transcriptional, proteomic and metabolomic analyses showed that reduced DKC1 levels in cSCC cells resulted in both an activation of the mevalonate pathway and the acquisition of an invasive phenotype.

overall_design: 6 samples were analysed (CTRL=3, DKCi=3)


title: The histone demethylase KDM5C functions as a tumor suppressor in AML by repression of bivalently marked immature genes

status: Public on Jan 11 2023

city: Copenhagen

first: Bo

last: Porse

address: Ole Maaløes Vej 5, 4

department: Finsen Laboratory and BRIC

country: Denmark

institute: University of Copenhagen


title: Comparative RNA-Seq transcriptome analyses of diabetic nerve and kidney disease

status: Public on Jan 12 2023

city: Grand Forks

first: Junguk

last: Hur

state: ND

address: 1301 N. Columbia Rd. Stop 9037

department: Biomedical Sciences

institute: University of North Dakota


title: The histone demethylase KDM5C functions as a tumor suppressor in AML by repression of bivalently marked immature genes (RNA-Seq)

summary: Epigenetic regulators are frequently mutated in acute myeloid leukemia (AML). However, epigenetic dysregulation in AML extends beyond recurrently mutated factors and only little is known about the potential drivers in this context. Identification and characterization of novel epigenetic drivers impacting on AML biology will not only improve our basic understanding of AML but may also uncover novel options for therapeutic intervention.  To uncover novel epigenetic regulators in AML, we performed an in vivo short hairpin RNA (shRNA) screen in the context of CEBPA mutant AML. We identified the H3K4me2/3 demethylase KDM5C as a novel tumor suppressor in AML.  We found that lower Kdm5c/KDM5C expression levels are associated with accelerated growth of human and murine AML cell lines. In a CEBPA mutant AML mouse model, Kdm5c knockdown resulted in a more aggressive, immature and short-latency phenotype. Mechanistically, we show that knockdown of Kdm5c increased H3K4me3-levels globally. This translated into the up-regulation of a group of bivalently marked immature genes resulting in a de-differentiation phenotype which could be reversed by modulating levels of pro-differentiating factors. Finally, we could demonstrate that low levels of KDM5C was associated with a decrease in long-term disease-free survival, specifically in female patients. This emphasizes the clinical relevance of our findings and identifies KDM5C as a novel sex-specific tumor suppressor in AML.

overall_design: Examined transcriptome from control-shRNA-control and Kdm5c-shRNA Lp30 cells in biological triplicates

middle: T

first: Mette

middle: L

last: Trempenau

first: Mikkel

middle: B

last: Schuster

first: Sachin

last: Pundhir

first: Adrija

last: Kalvisa

first: Ying

last: Ge

first: Frederik

middle: O

last: Bagger

first: Pavel

last: Shliaha

first: Patrycja

last: Sroczynska

first: Julian

last: Walfridsson

first: Ole

middle: N

last: Jensen

first: Kristian

last: Helin


title: Venetoclax, alone or in combination with the BH3-mimetic S63845, depletes HIV-1 latently infected cells and delays rebound in humanized mice.

city: Melbourne

first: Dylan

last: Sheerin

state: VIC

address: 1G Royal Parade

country: Australia

institute: WEHI

summary:
To determine the transcriptional changes that occur in CD4+ T cells from PLWH following ex vivo treatment with a pro-apoptotic inhibitor of Bcl-2.
Comparisons were performed using bulk RNA-seq data from human CD4+ T cells isolated from PLWH, 24 hours post-treatment with a pro-apoptotic inhibitor of Bcl-2 at variopus concentrations.

overall_design: Comparative gene expression profiling analysis of human CD4+ T cell bulk RNA-seq data. Contrasts were made between cells treated with various concentrations of a pro-apoptotic inhibitor of Bcl-2 and cells treated with DMSO.

first: Philip

last: Arandjelovic


title: Acute and Long-Term/Resistant Gene Expression Changes in H23 Cells Due to Sotorasib Treatment

status: Public on Jan 06 2023

city: Duarte

first: Charles

middle: David

last: Warden

state: CA

address: 1500 East Duarte Rd

department: Department of Molecular and Cellular Biology

institute: City of Hope

summary: To better understand the mechanism of acquired resistance to sostorasib, we selected the H23 cells to develop an isogenic sotorasib resistant cell line. H23 cells were treated for a period of 45 days with increasing concentrations of sotorasib until the develo resistance to sostorasib.

overall_design:
Duplicates are provided for Control, "Parent" with Sotorasib treatment, and "Resistant" from Sotorasib treatment

**Only processed data was deposited because we do not know the consent for the NCI-H23 cell line (from 1976, based upon a colleague’s reference to Phelps et al. 1996 / PMID 8806092).**

first: Atish

last: Mohanty

first: Ravi

last: Salgia


title: The histone demethylase KDM5C functions as a tumor suppressor in AML by repression of bivalently marked immature genes (ChIP-seq)

first: Bo

last: Porse

summary:
Epigenetic regulators are frequently mutated in acute myeloid leukemia (AML). However, epigenetic dysregulation in AML extends beyond recurrently mutated factors and only little is known about the potential drivers in this context. Identification and characterization of novel epigenetic drivers impacting on AML biology will not only improve our basic understanding of AML but may also uncover novel options for therapeutic intervention.
To uncover novel epigenetic regulators in AML, we performed an in vivo short hairpin RNA (shRNA) screen in the context of CEBPA mutant AML. We identified the H3K4me2/3 demethylase KDM5C as a novel tumor suppressor in AML.
We found that lower Kdm5c/KDM5C expression levels are associated with accelerated growth of human and murine AML cell lines. In a CEBPA mutant AML mouse model, Kdm5c knockdown resulted in a more aggressive, immature and short-latency phenotype. Mechanistically, we show that knockdown of Kdm5c increased H3K4me3-levels globally. This translated into the up-regulation of a group of bivalently marked immature genes resulting in a de-differentiation phenotype which could be reversed by modulating levels of pro-differentiating factors. Finally, we could demonstrate that low levels of KDM5C was associated with a decrease in long-term disease-free survival, specifically in female patients. This emphasizes the clinical relevance of our findings and identifies KDM5C as a novel sex-specific tumor suppressor in AML.

overall_design: ChIP-seq of H3K4me1, H3K4me3, H3K27me3, and H3K27ac in shControl versus shKdm5c Lp30 cells. ChIP-seqs were performed in biological duplicates.

last: KalviÅ¡a

first: Marta

last: Tapia


title: MYC disrupts transcriptional and metabolic circadian oscillations in cancer and promotes enhanced biosynthesis

status: Public on Jan 03 2023

city: Rochester

first: Brian

middle: James

last: Altman

state: NY

address: 601 Elmwood Avenue Box 633

department: Biomedical Genetics

institute: University of Rochester


title: Effect of S. epidermidis phenol-soluble modulins on primary human keratinocytes.

status: Public on Jan 01 2023

city: La Jolla

first: Michael

middle: R

last: Williams

address: 9500 Gilman Drive

department: Dermatology

institute: UC San Diego

summary:
To investigate the effect of synthetic phenol-soluble modulins (PSMs) secreted by S. epidermidis on primary keratinocytes.
We then performed gene expression profiling analysis using data obtained from RNA-seq of 4 different cells at two time points.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for 70% confluent neonatal prmary human epidermal keratinocytes (48h 2mM CaCl2 pre-differentiation ) followed by 6h synthetic 10uM PSM treatment.

first: Richard

last: Gallo


title: Circadian time-series RNA-sequencing of SHEP and SKNAS neuroblastoma cells with inducible N-MYC-ER

summary: The molecular circadian clock, which controls rhythmic 24-hour oscillation of genes, proteins, and metabolites, is disrupted across many human cancers.  Deregulated expression of MYC oncoprotein has been shown to alter expression of molecular clock genes, leading to a disruption of molecular clock oscillation across cancer types.  However, it remained unclear how this loss of molecular clock oscillation impacted global gene expression and metabolism in cancer, and what benefit cancer cells might gain from suppressing clock oscillation.  We hypothesized that MYC suppresses oscillation of gene expression and metabolism to instead upregulate pathways involved in biosynthesis in a static, non-oscillatory fashion.  To test this, we utilized cells from distinct cancer types with inducible MYC or the closely related N-MYC to determine, using detailed time-series RNA-sequencing and metabolomics, the extent to which MYC activation disrupts global oscillation of genes, gene expression, programs, and metabolites.  We focused our analyses on genes, pathways, and metabolites that changed in common across multiple cancer cell line models.  We report here that MYC disrupted over 85% of oscillating genes, while instead promoting enhanced ribosomal and mitochondrial biogenesis and suppressed cell attachment pathways.  Notably, when MYC is activated, biosynthetic programs that were formerly circadian flipped to being upregulated in an oscillation-free manner.  Further, activation of MYC ablates the oscillation of nutrient transporter glycosylation while greatly upregulating transporter expression, cell surface localization, and intracellular amino acid pools.  Finally, we report that MYC disrupts metabolite oscillations and the temporal segregation of amino acid metabolism from nucleotide metabolism.  Our results demonstrate that MYC disruption of the molecular circadian clock releases metabolic and biosynthetic processes from circadian control, which may provide a distinct advantage to cancer cells.

overall_design: We activated N-MYC-ER in cells for 24 hours with 4-hydroxytamoxifen (4OHT, MYC-ON), or used vehicle control (MYC-OFF).  We then entrained cells circadian rhythms with dexamethasone.  24 hours after dexamethasone treatment, cells were then collected every 4 hours for up to 52 hours, and RNA was extracted.  CT refers to circadian time, ie, hours after dexamethasone entrainment.  RNA at approximately 37 ng/µL was submitted to Novogene Co., was analyzed by BioAnalyzer and determined to have an average RNA Integrity Number (RIN) of 9.8.  RNA-sequencing was performed on polyadenylated mRNAs using an Illumina NovaSeq 6000 as 150 base paired end sequencing, yielding an average of 54.7 million reads per sample (when adding together both paired ends).  Reads were mapped with Salmon, and collapsed to gene level with Tximport.  Two biological replicate experiments were performed in SHEP, and a single replicate was performed in SKNAS.

first: Chi

middle: V

last: Dang


title: A TDP-43 acetylation-mimic mutation that disrupts RNA-binding drives FTLD-like neurodegeneration in a mouse model of sporadic TDP-43 proteinopathy

status: Public on Jan 09 2023

city: Boston

first: Jeremy

last: Simon

address: 450 Brookline Ave

department: Department of Data Science

institute: Dana-Farber Cancer Institute

summary: TDP-43 proteinopathies including frontotemporal lobar dementia (FTLD) and amyotrophic lateral sclerosis (ALS) are devastating neurodegenerative disorders characterized by aggregation and mislocalization of the nucleic-acid binding protein TDP-43 and subsequent neuronal dysfunction. Here, we developed an endogenous model of sporadic TDP-43 proteinopathy based on the principle that disease-associated TDP-43 acetylation at lysine 145 (K145) alters TDP-43 conformation, impairs its RNA-binding capacity, and induces downstream mis-regulation of target genes. Expression of aberrant acetylation-mimic TDP-43K145Q resulted in stress-induced phase-separated nuclear TDP-43 foci formation and loss-of-TDP-43-function in mouse primary neurons and human induced pluripotent stem cell (iPSC)-derived neurons. Aged mice harboring the single TDP-43K145Q mutation recapitulate several key hallmarks of neurodegenerative proteinopathies, including progressive TDP-43 phosphorylation and insolubility, cytoplasmic mis-localization, widespread transcriptomic and splicing alterations, and cognitive dysfunction. Our study supports a model in which aberrant TDP-43 acetylation drives neuronal dysfunction and cognitive decline through alternative splicing and transcription of genes important in synaptic plasticity and apoptosis, providing a new paradigm to interrogate FTLD disease mechanisms and uncover disease-modifying therapeutics.

overall_design: Total RNAseq of mouse hippocampus and cortex, comparing TDP43-KQ vs TDP43-WT in 18-month-old male and female animals

first: Julie

middle: C

last: Necarsulmer

first: Todd

last: Cohen


title: Oncogene-like addiction to aneuploidy in human cancers

city: New Haven

first: Jason

last: Sheltzer

state: CT

address: 300 George Street

department: Surgery

institute: Yale University

summary: Most cancers exhibit aneuploidy, but its functional significance in tumor development is controversial. Here, we describe ReDACT (Restoring Disomy in Aneuploid cells using CRISPR Targeting), a set of chromosome engineering tools that allow us to eliminate specific aneuploidies from cancer genomes. Using ReDACT, we created a panel of isogenic cells that have or lack common aneuploidies, and we demonstrated that trisomy of chromosome 1q is required for malignant growth in cancers harboring this alteration. Mechanistically, gaining chromosome 1q increases the expression of MDM4 and suppresses TP53 signaling, and we show that TP53 mutations are mutually-exclusive with 1q aneuploidy in human cancers. Thus, specific aneuploidies play essential roles in tumorigenesis, raising the possibility that targeting these “aneuploidy addictions” could represent a novel approach for cancer treatment.

overall_design:
Isogenic cell lines were generated lacking recurrently observed chromosomal gains  in cancer

Processed RNA-Seq data used for analysis is provided for all cell lines

==================================================
Submitter comment concerning missing raw data (GSM6921879-GSM6921888):
Raw files for A2780 were misplaced by a former lab member during the course of this work; the lab also changed affiliations during this time -- resulting in an inability to recover raw sequencing files. However, the A2780 processed results were still used in drawing conclusions within the associated manuscript.
==================================================

first: Vishruth

last: Girish

first: Asad

middle: A

last: Lakhani

first: Sarah

last: Thompson

first: Christine

last: Scaduto

first: Ryan

last: Hagenson


title: RNA sequencing of ex vivo human colonic mucosal Vg2/3/4+ CD103+ and CD103negative T cells

status: Public on Dec 31 2022

city: London

first: Philip

last: East

address: Midland Road

country: United Kingdom

institute: The Francis Crick Institute

summary: Purpose: to characterise the steady state gene expression and transcriptomic characteristic of tissue residernt human colonic mucosal gd T cells from controls undergoing routine colonoscopy.

overall_design: Methods: 12 fresh pinch biopsies were obtained per patient from 4 control patients underoing screening colonoscopy and immediately dissociated using a Miltenyl tumour dissociation protocol. Cells were FACS sorted according to their surface phenotype Vg2/3/4 CD103+ or CD103neg. For the first 3 donors these were frozen and sent to Genewiz for RNA extrraction library preparation and sequencing on an Illumina HiSeq. For the final donor, RNA was purified immediately after the sort and libraries were prepared and sequenced on an Illumina HiSeq 2500 at the Francis Crick Institute in London.

first: Robin

last: Dart

first: Adrian

last: Hayday

first: Tim

last: Recaldin


title: The histone demethylase KDM5C functions as a tumor suppressor in AML by repression of bivalently marked immature genes (ChIP-Seq)

first: Bo

last: Porse

summary: Epigenetic regulators are frequently mutated in hematological malignancies including acute myeloid leukemia (AML). However, epigenetic dysregulation in AML extends beyond recurrently mutated factors, and only little is known about the potential drivers in this context. Identification and characterization of novel epigenetic drivers affecting AML biology will not only improve our basic understanding of AML, but can also uncover novel options for therapeutic intervention.  To uncover novel epigenetic regulators in AML, we performed an in vivo short hairpin RNA (shRNA) screen in the context of Cebpa mutant AML. This led to the identification of the Histone 3 Lysine 4 (H3K4) demethylase, KDM5C, as a novel tumor suppressor in AML. KDM5C potentially functions as a transcriptional repressor via its demethylase activity at promoters, and dysregulation could therefore have widespread consequences.  Here, we found that reduced Kdm5c/KDM5C expression is associated with accelerated growth in both human and murine AML cell lines. In vivo, Kdm5c knockdown in a Cebpa mutant AML mouse model resulted in a more aggressive, immature and short-latency phenotype. Mechanistically, we show that knockdown of Kdm5c increased H3K4me3 globally. This translated into the up-regulation of a group of bivalently marked immature genes, resulting in a de-differentiation phenotype which could be reversed by modulating levels of pro-differentiation factors. Finally, we demonstrated that low levels of KDM5C were associated with a decrease in long-term disease-free survival, specifically in female patients. This emphasizes the clinical relevance of our findings and identifies KDM5C as a novel female-biased tumor suppressor in AML.

overall_design: ChIP-seq of H3K4me1, H3K4me3 and H3K27ac in shControl versus shKdm5c Lp30 cells. ChIP-seqs were performed in biological duplicates.

first: Mette

last: Trempenau

first: Mikkel

last: Schuster

first: Sachin

last: Pundhir

first: Adrija

last: Kalvisa

first: Ying

last: Ge

first: Frederik

last: Bagger

first: Pavel

last: Shliaha

first: Patrycja

last: Sroczynska

first: Julian

last: Walfridsson

first: Ole

last: Jensen

first: Kristian

last: Helin


title: Genome-wide enhancer-gene regulatory maps link causal variants to target genes underlying human colorectal cancer risk

first: Can

last: Chen

overall_design: Refer to individual Series


title: mRNAseq profiling of Bifidobacterium longum-stimulated neonatal and adult T-cells

city: Braunschweig

first: Robert

last: Geffers

address: Inhoffenstr. 7

department: Dep. Molecular Bacteriology

country: Germany

institute: HCI - Helmholtz Centre for Infection Research

summary: To study the differentiation of Bifidobacterium longum-specific T cells, we stimulated neonatal or naive adult T cells with B. longum-pulsed monocytes and compared them to resting cells from the same donor.

overall_design: Activated T cells from different human donors were isolated by fluorescence-activated cell sorting (FACS) after 3-day co-culture with B. longum-pulsed monocytes and analysed by RNAseq.

first: Katrin

last: Vogel

first: Denny

last: Schanze

first: Monika

last: Brunner-Weinzierl


title: Spatial compartmentalization of signalling imparts source-specific functions on secreted factors.

city: Vancouver

first: Fabio

last: Rossi

state: BC

address: 2222 Health Sciences Mall

department: School of Biomedical Engineering

country: Canada

institute: University of British Columbia

summary: Efficient regeneration requires multiple cell types acting in a coordination. To better understand the intercellular networks involved and how they change when regeneration fails, we profiled the transcriptome of hematopoietic, stromal, myogenic, and endothelial cells over 14 days following acute muscle damage.

overall_design: Hematopoietic, stromal, myogenic, and endothelial cells were collected over 14 days following acute muscle damage and subjected to RNAseq. We used a novel bioinformatics pipeline to generate a time-resolved computational model of interactions.

first: Elena

last: Groppa

first: Lin

last: Yi

first: Tara

last: Stach

middle: W

last: Tung


title: Circadian time-series RNA-sequencing of U2OS osteosarcoma cells with inducible MYC-ER

first: Brian

last: Altman

overall_design: We activated MYC-ER in cells for 24 hours with 4-hydroxytamoxifen (4OHT, MYC-ON), or used vehicle control (MYC-OFF).  We then entrained cells circadian rhythms with dexamethasone.  24 hours after dexamethasone treatment, cells were then collected every 4 hours (replicate 1) or 2 hours (replicate 2) for up to 48 hours, and RNA was extracted.  CT refers to circadian time, ie, hours after dexamethasone entrainment.  RNA at approximately 100 ng/µL was submitted to the University of Pennsylvania Next Generation Sequencing Core, was analyzed by BioAnalyzer and determined to have an average RNA Integrity Number (RIN) of 9.9.  RNA-sequencing was performed on ribosome-depleted total RNA (replicate 1) or polyadenylated mRNAs as 100 base single-end sequencing using an Illumina HiSeq 4000, yielding an average of 74.3 million reads per sample for Replicate 1, and 40.9 million reads per sample for Replicate 2.  Reads were  mapped with Salmon, and collapsed to gene level with Tximport.

first: Chi

last: Dang


title: Effects of extracellular vehicles secreted from human-induced pluripotent stem cell-derived mesenchymal stem cells on the functional recovery of an ischemic stroke mouse model

city: Hong Kong

first: XIANWEI

last: SU

address: Shatin

institute: The Chinese University of Hong Kong

summary: To investigate the the expression profile and potential pathways involved in celluar ischemic stroke model, we established murine HT22 cell lines with oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro

overall_design: Comparative gene expression profiling analysis of RNA-seq data for HT22 cell line and  OGD/R with PBS , EVs (OGD, OGP, and OGE).

first: Xianwei

last: Su

first: Gang

last: Lu


title: Lipid droplets modulate autophagy receptor SQST-1/SQSTM1 dynamics and lifespan

city: Providence

first: Louis

last: Lapierre

address: 185 Meeting St.

institute: Brown

summary: RNA-seq performed for studying transcriptomic changes modulated by ATGL-1

overall_design: Comparison of transcript expression between Day 5 WT, daf-2 or ATGL-1 OE animals


title: Identification of Aurora B pathway involved in the anti-cancer effects by Paeoniae Radix extracts based on whole transcriptome analysis

city: Daejeon

first: Su-Jin

last: Baek

address: 1672, Yuseong-daero

country: South Korea

institute: KOREA INSTITUTE of ORIENTAL MEDICINE

summary: we profiled the change in genome-wide gene expression of human lung cancer cells in response to treatment of water and ethanol extracts of PR and its ingredients in a dose dependent manner to investigate PR efficacy at the molecular pathway level.

overall_design: Total whole transcritome profiles treated with water extract of Paeoniae Radix (PR), ethanol extract of PR, and eight ingredients in A 549 lung cancer cell lines.

first: Seongwon

last: Cha

first: Jin-Mu


title: Modeling the initiation of Ewing sarcoma tumorigenesis in human Embryonic Stem Cells

city: Barcelona

first: Júlia

last: Perera-Bel

address: Doctor Aiguader, 88

institute: Hospital del Mar Research Institute

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


title: Modeling the initiation of Ewing sarcoma tumorigenesis in human Embryonic Stem Cells [RNA-seq]

summary: Ewing sarcoma family of tumors (ESFT) is a uniquely human, highly aggressive bone and soft tissue malignancy peaking during adolescence characterized by EWSR1/ETS rearrangements. EWSR1/FLI1 expression is only tolerated in embryonic and mesenchymal stem cells (hESC and hMSC, respectively) that, although acquire ESFT transcriptional signatures, are devoid of tumorigenic potential. Here we report that ectopic EWSR1/FLI1 expression in hESC allows in vivo differentiation towards the three germ layers. In vitro, teratoma-derived hMSCs are devoid of transformation abilities. In vivo, these hMSCs led to the generation of T-cell lymphomas and ESFT-like tumors, composed of small-round blue cells. This new experimental approach constitutes a testing bench for the biology of translocation-dependent developmental tumors, from acute lymphoblastic leukemia to a variety of sarcomas.

overall_design: mRNA profiles of tumors derived from human Mesenchymal Stem Like Cells: two lymphomas from control hMSLCs, two lymphomas from EF_hMSLCs and two sarcomas from EF_hMSLCs

first: Hernández-Muñoz

last: Inmaculada


title: Modeling the initiation of Ewing sarcoma tumorigenesis in human Embryonic Stem Cells [expression array]

overall_design: 10 samples were analyzed: EWSFLI1 (6) and Control (4)


title: Nodal coordinates the anterior-posterior patterning of germ layers and induces head formation in zebrafish explants.

status: Public on Dec 22 2022

city: Hang Zhou

first: Tao

last: cheng

state: Zhe Jiang

address: 886 Yuhangtang Road

department: Institute of genetics

institute: Zhejiang University

summary:
Purpose: To investingate cell types in wild-type zebrafish explants.
Methods:  Wild-type explants (injected with phenol red) were harvested at 10hpf. Libraries were prepared using Chromium Controller and Chromium Single Cell 3’Library & Gel Bead Kit v3 (10x Genomics, PN-1000075) according to the manufacturer’s protocol for 10000 cells recovery.
Results: A total of 9,968 single-cell transcriptomes were collected after stringent quality control measures.
Conclusions: 6 Cell types  were identified, wild-type explants mainly contains the anterior neural ectoderm and epidermis at 10 hpf.

overall_design: Wild-type zebrafish explants were harvested at 10hpf for scRNA-seq.

last: Cheng

first: Yan-Yi

last: Xing


title: RNA-seq data of cGP-treated human fetal neural stem cells

city: Tsukuba

first: Kazutoshi

last: Murotomi

address: 1-1-1 Higashi

institute: Advanced Industrial Science and Technology

summary: GP protects oxidative stress-induced cell damage. The goals of this study are to compare NGS-derived  transcriptome profiling (RNA-seq) with or without cGP in human neural stem cells

overall_design: Examination of different gene expressions after cGP treatment in human neural stem cells

first: Masakazu

last: Namihira


title: Accurate age prediction from blood using a small set of DNA methylation sites and a cohort-based machine learning algorithm

status: Public on Jan 20 2023

city: Jerusalem

first: Tommy

last: Kaplan

address: Givat Ram Campus

department: School of Computer Science and Engineering

country: Israel

institute: Hebrew University

type:
Methylation profiling by array
Third-party reanalysis

summary: Chronological age prediction from DNA methylation sheds light on human aging, indicates poor health and predicts lifespan. Previous studies developed methylation clocks based on linear regression models on methylation array data. While accurate, these models are limited to fixed-rate changes in methylation levels across age. Moreover, the high cost of methylation arrays, compared to targeted-PCR sequencing, hinders widespread utility of such predictors.  We present an AI-based alternative termed GP-age, which uses a non-parametric approach based on Gaussian Process Regression of a large cohort of ~12K blood methylomes. Given a new blood sample, methylation levels are compared to the cohort samples, which are then weighted to predict the query age. Using only 30 CpG sites, our approach outperforms state-of-the-art methylation clocks that use hundreds of sites, with a median error of 2.1 years (on held-out data). Our model was also applied to sequencing-based data yielding highly accurate predictions.  Overall, we provide an accessible alternative to current array-based methylation clocks, with future applications in aging research, forensic profiling, and monitoring epigenetic processes in transplantation medicine and cancer.

relation:
Reanalysis of: GSE55763
Reanalysis of: GSE84727
Reanalysis of: GSE154566
Reanalysis of: GSE51032
Reanalysis of: GSE87648
Reanalysis of: GSE157131
Reanalysis of: GSE73103
Reanalysis of: GSE105018
Reanalysis of: GSE147221
Reanalysis of: GSE72680
Reanalysis of: GSE64495
Reanalysis of: GSE103657
Reanalysis of: GSE42861
Reanalysis of: GSE72775
Reanalysis of: GSE40279
Reanalysis of: GSE69270
Reanalysis of: GSE41169
Reanalysis of: GSE36054
Reanalysis of: GSE30870

overall_design: Re-published data of Bisulphite converted DNA from 11,910 whole-blood samples hybridised to the Illumina Infinium 450k Human Methylation Beadchip. The processed beta values of age-correlated 2,374 CpG sites and the ages of the donors are included.

first: Miri

last: Varshavsky

first: Gil

last: Harari

first: Benjamin

last: Glaser

first: Yuval

last: Dor

first: Ruth

last: Shemer


title: Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation

status: Public on Dec 20 2022

city: Kansas City

first: Kaelan

middle: Joseph

last: Brennan

state: MO

address: 1000 East 50th Street

institute: Stowers Institute for Medical Research

platform_organism:
Drosophila melanogaster
synthetic construct


title: Integrated systems-biology platform for power-to-gas technology

city: Tübingen

first: Bastian

last: Molitor

state: Baden Württemberg

address: Schnarrenbergstr. 94-96

department: Center for Applied Geosciences

institute: University of Tübingen

summary:
Methanogenesis allows methanogenic archaea (methanogens) to generate cellular energy for their growth while producing methane. Hydrogenotrophic methanogens thrive on carbon dioxide and molecular hydrogen as sole carbon and energy sources. Thermophilic and hydrogenotrophic Methanothermobacter spp. have been recognized as robust biocatalysts for a circular carbon economy and are now applied in power-to-gas technology. Here, we generated the first manually curated genome-scale metabolic reconstruction for three Methanothermobacter spp.. We investigated differences in growth performance and gas consumption/production of three wild-type strains and one genetically engineered strain in two independent quadruplicate chemostat bioreactor experiments: 1) with molecular hydrogen and carbon dioxide; and 2) with sodium formate. In the first experiment, we found the highest methane production rate for Methanothermobacter thermautotrophicus ΔH, while Methanothermobacter marburgensis Marburg reached the highest biomass growth rate.
We collected statistically reliable transcriptomics and proteomics data sets from these steady-state bioreactors, which we integrated within our genome-scale metabolic models. The implementation of an pan-model that contains combined reactions from all three microbes allowed us to perform an interspecies comparison of the complete omics data set. While the observed differences in the growth behavior cannot be fully explained, the comparison enabled us to identify crucial differences in growth-related pathways, such as formate anabolism. In the second experiment, we found stable growth with a M. thermautotrophicus ΔH plasmid-carrying strain on formate with similar performance parameters compared to wild-type Methanothermobacter thermautotrophicus Z-245.  The results of the two studies demonstrate the advantages of an integrative approach using fermentation and omics data with genome-scale modeling for the investigation of lesser studied metabolisms, and the biotechnological potential of Methanothermobacter spp. as production platform hosts.

sample_organism:
Methanothermobacter thermautotrophicus
Methanothermobacter marburgensis

overall_design: Individual (and comparative) gene expression analysis of RNA-seq data taken during exponential growth (bioreactors at steady state) for Methanothermobacter thermautotrophicus ΔH, Methanothermobacter thermautotrophicus Z-245, and Methanothermobacter marburgensis Marburg. Each microbe has 4 biological replicates corresponding to 4 bioreactors.

first: Isabella

last: Casini

first: Tim

last: McCubbin

first: Sofia

last: Esquivel-Elizondo

first: Guillermo

middle: G

last: Luque

first: Daria

last: Evseeva

first: Christian

last: Fink

first: Sebastian

last: Beblawy

first: Nicholas

middle: D

last: Youngblut

first: Daniel

middle: H

last: Huson

first: Andreas

last: Dräger

middle: E

last: Ley

first: Esteban

last: Marcellin

first: Lars

last: Angenent


title: Expression data from gastric tissues with non-atrophic gastritis, intestinal metaplasia, and gastric cancer

status: Public on Dec 30 2022

city: Jinan

first: Ai

last: Li

address: 山东省济南市历下区文化西路44号山东大学趵突泉校区9号公寓楼

institute: 山东大学

summary: We identified several hub genes and key pathways associated with GC and IM initiation and progression by analyzing the DEGs, which provided a detailed molecular mechanism underlying GC and IM occurrence and progression.

overall_design: RNA profiles of 30 gastric tissue samples from patients with non-atrophic gastritis, intestinal metaplasia, and gastric cancer were generated by high throughput sequencing.

first: Li

last: Ai


title: Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation [PBM]

last: Brennan

summary: Spatiotemporal gene regulation during embryonic development is driven by cis-regulatory DNA sequences called enhancers. Enhancers are activated through a combination of transcription factors (TFs) that bind to short sequence motifs within these sequences, but the order of events by which TFs read out motifs is not clear. Some TFs can only bind chromatin that is already accessible, while other TFs called pioneers can open chromatin themselves. Identifying motifs and the order by which they drive chromatin accessibility is very challenging. The recent implementation of convolutional neural networks, which learn complex cis-regulatory sequence rules that are predictive for genomics data, provides an unprecedented opportunity to dissect this problem. Here, we trained base-resolution deep learning models and applied them to high-resolution TF binding and chromatin accessibility data from the well-studied early Drosophila embryo. We uncover a clear hierarchical relationship between the pioneer Zelda and the TFs involved in the spatiotemporal patterning of the embryo, consistent with Zelda being a pioneer. However, the models predict that patterning TFs can also augment chromatin accessibility in a context-specific manner. Using a series of Drosophila mutant strains, we find that the two types of TFs increase chromatin accessibility by distinct mechanisms. Zelda’s pioneering is proportional to motif affinity, while the patterning TFs specifically increase chromatin accessibility when they mediate enhancer activation. This was conclusive because Dorsal can function both as activator and repressor, and the effect on chromatin accessibility depended on Dorsal’s transactivation effect and not on its binding per se. In conclusion, chromatin accessibility occurs in two phases: one through pioneering, which makes regions first accessible but not necessarily active, and a second when the correct combination of transcription factors lead to enhancer activation.

overall_design: Protein binding microarray (PBM) experiments were performed for Zelda proteins. Briefly, the PBMs involved binding GST-tagged DNA-binding proteins to two double-stranded 44K Agilent microarrays, each containing a different DeBruijn sequence design, in order to determine their sequence preferences. Details of the PBM protocol are described in Berger et al., Nature Biotechnology 2006.

middle: J

first: Melanie

last: Weilert

first: Sabrina

last: Krueger

first: Anusri

last: Pampari

first: Hsiao-Yun

last: Liu

first: Ally

last: Yang

first: Jason

last: Morrison

first: Timothy

last: Hughes

first: Christine

last: Rushlow

first: Anshul

last: Kundaje

first: Julia

last: Zeitlinger


title: Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation [ChIP-nexus]

first: Kaelan

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-nexus) for Zelda, Dorsal, Twist, Bicoid, Caudal, and GAGA Factor, as well as H3K27ac and H3K4me1 ChIP-seq experiments, in 2-3 hour after egg laying (AEL) Drosophila melanogaster embryos.


title: Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation [ATAC-seq]

overall_design: Assay for transposase-accessible chromatin DNA-sequencing (ATAC-seq) in wt Drosophila melanogaster embryos, zld- mutant embryos, gd7 mutant embryos, and cic6 mutant embryos. ATAC-seq experiments were done in a time course manner in 30 minute windows spanning the maternal-to-zygotic transition.


title: PIKFYVE Inhibition Mitigates Disease in Models of Diverse Forms of ALS [1]

status: Public on Dec 18 2022

city: Los Angeles

first: Justin

last: Ichida

address: 1425 San Pablo Street, BCC 305

department: Department of Stem Cell Biology and Regenerative Medicine

institute: University of Southern California

summary: RNA sequencing analysis of human iPSC-derived motor neurons generated from one C9ORF72 ALS/FTD patient line, treated with DMSO or Apilimod. The goal of this study is to evaluate the effect of PIKFYVE inhibitor in rescuing ALS motor neuron degeneration.

overall_design: Gene expression profiling analysis of RNA-seq data for the effect of PIKFYVE inhibitor, Apilimod, on C9ORF72 ALS/FTD iPSC-derived motor neurons.

last: K Ichida


title: Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses

status: Public on Dec 08 2022

first: Shenglin

last: Mei

address: 10 Shattuck Street

institute: Harvard medical school (DMBI)

summary:
Novel single cell technologies have paved the way for the characterization and improved biological understanding of prostate cancer, here we performed scRNA-seq on 20 human prostate tumors and their matched adjacent-normal tissues in addition to 5 healthy prostate tissues. We have provided a high-resolution transcriptome-wide expression analysis (droplet-based 10x genomics) to examine tumors from patients with localized prostate cancer across a spectrum of primary tumor stages and grades.

Novel single cell technologies have paved the way for the characterization and improved biological understanding of clear cell renal cell carcinoma (ccRCC) where the focus has been mostly on the immunological compartments of the tumor microenvironment (TME). However, the identification of metastatic tumor cell clones, and the stromal compartments of TME of untreated ccRCC patients still remains to be elucidated. Here we perform single-cell RNA-sequencing on treatment naive ccRCC and adjacent normal kidney tissue.

overall_design: Human prostate tissue were disaggregated and profiled using the Chromium Single Cell 3’ Library and Gel Bead Kit v2 (10X Genomics).


title: Choroid Plexus-Derived Insulin Inhibits Feeding via Direct Signaling through Arcuate Nucleus

status: Public on Dec 15 2022

city: Baltimore

first: Josephine

middle: M.

last: Egan

state: MD

address: BRC Suite 100, 251 Bayview Boulevard

department: Laboratory of Clinical Investigation

institute: National Institute on Aging - NIH

summary: The choroid plexus is an important source of trophic factors for the developing and mature brain. Recently we described the expression and production of mature insulin in epithelial cells of the choroid plexus, and how its secretion can be modulated by serotonin through Htr2c, a metabotropic receptor that signals via Gq. To understand the function of this choroid plexus-derived insulin, here we describe a way to genetically target epithelial cells of the choroid plexus using a viral vector. With this, we modulated insulin expression and evaluated behavior. Insulin overexpression in the choroid plexus of wild type mice led to an inhibition in feeding, whereas insulin knockdown in choroid plexus of Ins1-/-Ins2fl/fl mice promoted discrete increases in food intake, especially after a period of fasting. Insulin overexpression in choroid plexus induced roust transcriptomic changes in the hypothalamus, most of which related to axonal growth and synapse-related processes. Finally, activation of Gq signaling in insulin-overexpressing choroid plexuses led to acute AKT phosphorylation in neurons of the arcuate nucleus, suggesting a direct action, through the CSF, of choroid plexus-derived insulin on the hypothalamus. Taken together our findings prove that the choroid plexus is a relevant source of insulin in the central nervous system, with physiological implications in feeding behavior. We believe that choroid plexus-derived insulin has to be taken into consideration in future work pertaining insulin actions in the brain.

overall_design: Comparative gene expression profiling and analysis of RNA-Seq data from the choroid plexus (CP) and hypothalamus (HT) of mice with overexpression of Ins2 gene in the CP.

first: Caio

last: Mazucanti

first: Vernon

last: Kennedy

first: Jane

last: Tian

first: Qing-Rong

first: Hasitha

last: Premathilake

first: Maire

last: Doyle

first: Jennifer

last: O’Connell

first: Simonetta

last: Camandola

middle: M


title: PARP1 gene knockout suppresses expression of DNA Base Excision Repair genes

status: Public on Dec 01 2022

city: Novosibirsk

first: Maxim

last: Ri

address: Lavrenteva st. 6

country: Russia

institute: LLC AcademGene

summary: PARP1 is a member of various DNA repair pathways - main target for anti-cancer treatment.  We evaluated the effect of topotecan and TDP1 Inhibitor in HEK293 wild-type and PARP1 knockout cells on the gene expression

overall_design: Knockout HEK293A cell line was generated using the CRISPR/Cas9 method. gRNA were design against region with constitutive protein-encoding exons of Parp1 gene. Then, we performed comparative gene expression profiling analysis of RNA-seq data for HEK293 wild type cells and Parp1 KO under influnce of topotecan, OL9-119 and its combination.

first: Nadezhda

middle: S

last: Dyrkheeva

first: Anastasia

last: Malakhova

first: Aleksandra

middle: L

last: Zakharenko

first: Larisa

last: Okorokova

first: Dmitriy

last: Shtokalo

first: Sophia

last: Pavlova

first: Sergey

middle: P

last: Medvedev

first: Suren

last: Zakian

first: Anna

last: Nushtaeva

first: Marsel

last: Kabilov

first: Alexey

last: Tupikin

first: Olga

last: Luzina

first: Nariman

middle: F

last: Salakhutdinov

middle: I

last: Lavrik


title: Inhibition of netosis with PAD inhibitor attenuates endotoxin shock induced systemic inflammation

city: Kaifeng

first: Huanling

last: Yao

state: Henan

address: Jin Ming Avenue

department: School of Life Sciences

institute: Henan University

summary: Neutrophils play a pivotal role in innate immunity and participate in a range of immunological disorders. Excessive neutrophil extracellular traps formed at infection and tissue damage sites are detrimental to the local tissue and further exacerbate inflammation. Protein arginine deiminases mediate histone citrullination and NET formation thereby regulating endotoxin shock response. However, the molecular mechanisms are less known. Here we report that inhibition of netosis attenuates inflammation in a LPS induced lethal endotoxic shock model in mice. Albeit a higher number of neutrophils are accumulated in peritoneal cavity the primary inflammatory site, the level of inflammatory signals is greatly reduced after netosis inhibition with a PAD inhibitor. In lungs under endotoxic stress, gene expression analyses indicate that LPS induced a drastic increase in inflammatory gene expression. In contrast, lung tissue damage and inflammation were much reduced after PAD inhibition to reduce netosis. In summary, we found NET formation inhibition as a new avenue to manage inflammatory damages under endotoxic stress.

overall_design: We performed gene expression profiling analysis using data obtained from RNA-seq of 3 different treatment groups of mice lung tissue: control group with 3 samples, LPS group with 3 samples, and dual treatment group with PAD4 inhibitor pretreated and LPS with 2 samples.

first: Guojie

last: Cao

first: Zheng

last: Liu

first: Zhanchao

last: Yan

first: Senzhen

last: Wang

first: Yuehua

first: Zhengwei

last: Guo

first: Yanming


title: PIKFYVE Inhibition Mitigates Disease in Models of Diverse Forms of ALS [2]

first: Justin

last: Ichida

summary: RNA sequencing analysis of human iPSC-derived motor neurons generated from two C9ORF72 ALS/FTD patient lines, treated with negative control ASO (NC ASO) or PIKFYVE ASO. The goal of this study is to evaluate the effect of PIKFYVE suppression in rescuing ALS motor neuron degeneration.

overall_design: Gene expression profiling analysis of RNA-seq data for the effect of PIKFYVE suppression on C9ORF72 ALS/FTD iPSC-derived motor neurons.

last: K Ichida


title: Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation [Mnase-seq]

first: Kaelan

last: Brennan

overall_design: Micrococcal nuclease DNA sequencing (MNase-seq) in 2-3 hour after egg laying (AEL) Drosophila melanogaster embryos.

first: Melanie

last: Weilert

first: Sabrina

last: Krueger

first: Anusri

last: Pampari

first: Hsiao-Yun

first: Ally

last: Yang

first: Jason

last: Morrison

first: Timothy

middle: R

last: Hughes

first: Christine

last: Rushlow

first: Anshul

last: Kundaje

first: Julia

last: Zeitlinger


title: PIKFYVE Inhibition Mitigates Disease in Models of Diverse Forms of ALS

overall_design: Refer to individual Series


title: The admixed brushtail possum genome reveals invasion history in New Zealand and novel imprinted genes

status: Public on Nov 29 2022

city: Dunedin

first: Donna

last: Bond

address: 270 Great King Street

department: Department of Anatomy

country: New Zealand

institute: University of Otago

type: Methylation profiling by high throughput sequencing


title: CoLoC-seq, a high-throughput approach to profile organelle transcriptomes

status: Public on Nov 24 2022

city: Cologne

first: Konrad

middle: U.

last: Förstner

state: North Rhine-Westphalia

address: Gleueler Str. 60

department: Information Services

institute: ZB MED - Information Centre for Life Sciences

summary: Proper RNA localization is essential for normal gene expression in apparently all organisms. Detailed understanding of the extent of this phenomenon and the comprehensive profiling of subcellular transcriptomes rely on genome-wide, deep sequencing-based approaches. Among them, cell fractionation methods, that couple RNase treatment of isolated organelles to the RNA-seq of protected transcripts, remain most widely used, mainly because they do not require genetic modification of the studied system and can be easily implemented in any cells or tissues, including in non-model species. However, they suffer from rampant false-positives since incompletely digested contaminant RNAs can be erroneously identified as resident transcripts. Here we introduce Controlled Level of Contamination (CoLoC-seq) as a new subcellular transcriptomics approach that efficiently bypasses this caveat while preserving the key advantages of fractionation-based techniques. Instead of relying on the apparent abundance of individual RNA species in purified organelles, CoLoC-seq leverages their characteristic depletion dynamics in a gradient of exogenously added RNase, with or without intact organellar membranes, to distinguish between genuinely resident transcripts and merely abundant contaminants. Our generic approach robustly performed on human mitochondria and is in principle applicable to any membrane-bounded organelles, including plastids, vacuoles, and extracellular vesicles.

overall_design: The dataset includes two ordered series of human mitochondrial CoLoC-seq samples (biological replicates) and two corresponding series of mock CoLoC-seq samples (biological replicates). CoLoC-seq replicate #1 includes 9 samples, CoLoC-seq replicate #2 includes 10 samples, mock CoLoC-seq replicate #1 includes 9 samples, mock CoLoC-seq replicate #2 includes 10 samples. Each series begins with a reference sample corresponding to an untreated control ("0 µg/ml RNase A").

first: Damien

last: Jeandard

first: Akinyemi

last: Fasemore

middle: U

first: Alexandre

last: Smirnov


title: Expression data from human dental pulp stem cells and bone marrow mesenchymal stem cells

status: Public on Nov 10 2022

city: Beijing

first: 唐

last: 伟评

address: 2 Anzhen Rd, Chaoyang District,

institute: Beijing Institute of Heart Lung and Blood Vessel Diseases

summary:
To further reveal the mechanism of the senescence resistant property of mesenchymal stem cells from human, a gene expression profiling approach was used to compare the functional gene expression changes in BMMSCs and DPSCs with Affymetrix GeneChip Human Gene 1.0 ST arrays analysis.  Using bioinformatic analysis, we aimed to identify changes in genes and pathways in human DPSCs and BMMSCs .
Cells (BMMSCs and DPSCs) from healthy male subjects were seeded in 10 cm2 dishes and cultured until they reached 80 % confluence, and total RNA of DPSCs and BMMSCs were extracted and analyzed.

overall_design: Total RNA of DPSCs and BMMSCs were extracted using Trizol Reagent (Life Technologies). Following purification with a RNeasy kit (Qiagen, Valencia, CA, USA), cDNA was generated using One-Cycle Target Labeling and Control Reagents (Affymetrix, Santa Clara, CA, USA), and cRNA was created with a GeneChip IVT Labeling Kit (Affymetrix, Santa Clara, CA, USA). Biotin-labeled, fragmented (B200 nt) cRNA was hybridized to Affymetrix GeneChip Human Gene 1.0 ST arrays (Affymetrix).

first: Linsha

last: Ma


title: RNA-seq of wild-type and Ccm3 knock-out mouse cerebellar endothelial cells

status: Public on Nov 22 2022

city: Uppsala

first: Ying

last: Sun

address: Dag Hammarskjölds väg 20

country: Sweden

institute: Uppsala University

summary: The purpose of this study was to investigate the transcriptional regulation of endothelial cells in CCM pathology. We isolated cerebellar endothelial cells from healthy (wild-type) mice and from mice with an inducible endothelial-specific knock-out of the Ccm3 gene (Ccm3 knock-out). We prepared RNA libraries and sequenced the samples on a HiSeq2500 sequencing system with v4 chemistry from Illumina. We then performed a differential gene expression analysis to identify genes that play a role in CCM pathology.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for cerebellar endothelial cells between wild-type and Ccm3 gene knock-out mouse.

first: Maria

middle: A

last: Globisch

first: Favour

middle: C

last: Onyeogaziri

first: Suvi

last: Jauhiainen

first: Anthony

last: Yau

first: Fabrizio

last: Orsenigo

first: Lei

last: Conze

first: Maximiliano

last: Arce

first: Monica

last: Corada

first: Ross

middle: O

last: Smith

first: Charlotte

last: Rorsman

first: Veronica

last: Sundell

first: Dinesh

last: Fernando

first: Geoffrey

last: Daniel

first: Oscar

last: Mattsson

first: Henri

last: Savander

first: Alkwin

last: Wanders

first: Behnam

last: Jahromi

first: Aki

last: Laakso

first: Mika

last: Niemelä

first: Elisabetta

last: Dejana

first: Peetra

last: Magnusson


title: Transcriptome of human primary macrophages from X-linked adrenoleukodystrophy patients and healthy controls

status: Public on Nov 09 2022

city: Vienna

first: Jure

last: Fabjan

address: Spitalgasse 4

department: Department of Pathobiology of the Nervous System

country: Austria

institute: Medical University of Vienna

summary: Saturated very long-chain fatty acids (VLCFA, ≥ C22), enriched in brain myelin and innate immune cells, accumulate in X-linked adrenoleukodystrophy (X-ALD). The severest form, inherited dysfunction of the VLCFA transporter ABCD1, underlying X-ALD, causes brain myelin destruction with infiltration of pro-inflammatory skewed monocytes/macrophages. How VLCFA levels relate to macrophage activation is unclear. Using whole transcriptome sequencing of X-ALD macrophages, we revealed that VLCFAs prime human macrophage membranes for inflammation and increase factors involved in chemotaxis and invasion. When applied externally, mimicking lipid destruction in X-ALD lesions, VLCFAs did not activate toll-like receptors in healthy cells but provoked pro-inflammatory responses through scavenger receptor CD36-mediated uptake, cumulating in JNK signalling and expression of matrix degrading enzymes and chemokine release. Following pro-inflammatory LPS-activation, VLCFA accumulated in healthy macrophages but were rapidly cleared with onset of resolution by increasing VLCFA degradation through liver-X-receptor mediated upregulation of ABCD1. ABCD1 deficiency impaired VLCFA homeostasis and prolonged pro-inflammatory gene expression. Our study uncovers a pivotal role for ABCD1, a protein linked to neuroinflammation, and associated peroxisomal VLCFA degradation in regulating macrophage plasticity.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for macrophages derived from X-ALD patients and control blood-isolated monocytes.


title: The admixed brushtail possum genome reveals invasion history in New Zealand and novel imprinted genes [RNA-seq]

first: Donna

last: Bond

summary: The brushtail possum, Trichosurus vulpecula, is threatened in parts of its native range in Australia, but has also become a devastating mammalian pest following introduction into New Zealand from the mid 1800s. We have completed the first chromosome-level assembly of the possum genome and, using nuclear and mitochondrial analyses, traced southern New Zealand possums to distinct Tasmanian and mainland Australian subspecies, which have subsequently hybridised. This admixture is reflected in high levels of genetic diversity within New Zealand populations despite a founding bottleneck. Functional genomics revealed unique adaptations to altricial birth and extending weaning, including novel chemo-sensory genes, and at least four genes with imprinted, parent-specific expression not yet detected in other species (MLH1, EPM2AIP1, UBP1 and GPX7). We found that reprogramming of possum germline imprints and the wider epigenome was similar to eutherian mammals, except onset occurs after birth. Together, our data and analysis is useful for genetic-based control and conservation of possums, and contributes to understanding of the evolution of novel mammalian epigenetic traits such as germline methylation erasure and genomic imprinting.

overall_design: Comparative gene expression profiling analysis of RNA-seq data from a range of tissues (mostly liver) and developmental stages in the New Zealand common brushtail possum (Trichosurus vulpecula)

last: Ortega-Recalde

first: Melanie

middle: K

last: Laird

first: Takashi

last: Hayakawa

first: Kyle

last: Richardson

first: Finlay

last: Reese

first: Brooke

last: McIsaac-Williams

first: Bruce

last: Robertson

first: Yolanda

last: van Heezik

first: Amy

last: Adams

first: Wei-Shan

middle: V

last: Chang

first: Bettina

last: Haase

first: Jacquelyn

last: Mountcastle

first: Maximillian

last: Driller

first: Joanna

last: Collins

first: Francoise

last: Thibaud-Nissen

first: Paul

middle: D

last: Waters

first: Olivier

last: Fedrigo

first: Erich

last: Jarvis

first: Neil

last: Gemmell

first: Alana

last: Alexander

first: Timothy

last: Hore


title: Distinct mechanisms of germ cell factor regulation for an inductive germ cell fate

status: Public on Nov 16 2022

city: Providence

first: Gary

last: Wessel

state: RI

address: 185 Meeting St

department: Molecular Biology, Cell Biology & Biochemistry

institute: Brown University

summary: Here we employed single cell RNA sequencing to identify the transcriptional program of Nanos and Vasa positive cells and their changes during development. Our single cell sequencing analysis of six developmental stages in P. miniata revealed cell types derived from the three germ layers and expression of the germ cell genes Nanos and Vasa. We used these datasets to parse out 20 cell lineages of the embryo identified by this approach and to focus on the key transitions of germ cell gene expression and test their coexpression with key signaling components.

overall_design: Adult Patiria miniata animals were collected by either Peter Halmay (PeterHalmay@gmail.com) or Josh Ross (info@scbiomarine.com) off the Californian coast. Embryos were cultured essentially as described previously (Fresques et al., 2016). Embryos were cultured in filtered (0.2micron) sea water collected at the Marine Biological laboratories in Woods Hole MA, until the appropriate stage for dissociation. All embryos used in the study resulted from mating of one male and one female. Multiple fertilizations were initiated in this study and timed such that the appropriate stages of embryonic development were reached at a common endpoint. The embryos were then collected and washed twice with calcium-free sea water, and then suspended hyalin-extraction media (HEM) for 10-15 minutes, depending on the stage of dissociation. When cells were beginning to dissociate, the embryos were collected and washed in 0.5M NaCl, gently sheared with a pipette, run through a 40micron Nitex mesh, counted on a hemocytometer, and diluted to reach the appropriate concentration for the scRNA-seq protocol. Equal numbers of embryos were used in each time point and at no time were cells or embryos pelleted in a centrifuge (Oulhen et al., 2019).

first: Stephany

last: Foster

first: Nathalie

last: Oulhen


title: Hepatic transcriptome response to high dietary cholesterol intake in pig NAFLD model

city: Hangzhou

first: zhaowei

last: cai

state: Zhejiang

address: Binwen road 548

department: Laboratory Animal Research Center

institute: zhejiang chinese medical university

summary: The mechanisms by which cholesterol promotes NAFLD remain far less clear. Animal models are necessary to explore the pathogenesis and therapies of NAFLD. Several previous studies have shown that pig breeds can differ in their metabolic phenotype in response to high-energy diet. To investigate whether genetic background has profound effects on pig NAFLD phenotype and their metabolic response to dietary cholesterol intake, we performed RNA-Seq on liver tissues from two miniature pig breeds fed either standard or a high-fat and high-cholesterol diet for 6 months.

overall_design: Hepatic mRNA profiles of two miniature pig breeds fed either standard (SD) or a high-fat and high-cholesterol (HFC) diet were generated by deep sequencing, in triplicate, using Illumina HiSeq.

first: Zhaowei

last: Cai


title: The admixed brushtail possum genome reveals invasion history in New Zealand and novel imprinted genesed genes [WGBS]

first: Donna

last: Bond

overall_design: Global DNA methylation profiling of primordial germ cells from the male germline of the New Zealand common brushtail possum (Trichosurus vulpecula)

first: Oscar

last: Ortega-Recalde

first: Melanie

last: Laird

first: Takashi

last: Hayakawa

first: Kyle

last: Richardson

first: Finlay

last: Reese

first: Brooke

middle: E

last: McIsaac-Williams

first: Bruce

last: Robertson

first: Yolanda

last: van Heezik

first: Amy

last: Adams

first: Wei-Shan

last: Chang

middle: J


title: Intervention effect and mechanism of Tianhe Zhuifeng liquid extract on myofascial pain syndrome

status: Public on Nov 07 2022

first: Liu

middle: xue

last: ting

address: Dongzhimen

institute: China Academy of Chinese Medical Science

summary:
In order to explore the intervention effect of Tianhezhuifeng liquid extract on myofascial pain syndrome, we constructed an animal model of myofascial pain syndrome
We then performed gene expression profiling analysis using data obtained from pain point muscle tissue of typical samples

overall_design: Comparative gene expression profiling analysis of RNA-seq data for myofascial pain syndrome and Tianhe zhuifeng liquid extract improve myofascial pain syndrome

first: Xueting

last: Liu

first: Xia

last: Mao

first: Yanqiong

last: Zhang

last: Lin


title: MNase-seq analysis of the Methnocaldococcus jannaschii nucleoid reveals a general size-variable hypernucleosome architecture

status: Public on Oct 22 2022

city: Cardiff

first: Nicholas

middle: Anthony

last: Kent

address: Museum Avenue

department: School of Biosciences

institute: Cardiff University

summary: In eukaryotes, histone paralogues form obligate heterodimers such as H3/H4 and H2A/H2B that assemble into octameric nucleosome particles. Archaeal histones are dimeric and assemble on DNA into ‘hypernucleosome’ particles of varying sizes with each dimer wrapping 30 bp of DNA. These are likely composed of canonical and variant histone paralogues, but the function of these variants is poorly understood. Here, we characterise the structure and function of the histone paralogue MJ1647 from Methanocaldococcus jannaschii that has a unique C-terminal extension that enables MJ1647 homo-tetramerisation. The accompanying paper solves the crystal structure of MJ1647, but this part of the study specifically uses MNase-seq methodology to explore the hypernucleosome protection landscape of the in vivo M. jannaschii nucleoid.

overall_design: M. jannaschii cells were grown to log phase and nucleoids rendered accessible by detergent permeabilisation in an isotonic buffer. Two nucleoid samples were digested with different concentrations of MNase and nuclease-resistant and fragmented DNA species over a wide size range (typically 30 – 600bp) were converted to Illumina NGS libraries and sequenced in paired-end mode. A deproteinised gDNA sample was also digested with MNase to provide a control dataset to reveal any MNase-cleavage bias at the DNA sequence level. The mid-points between paired reads are then mapped to the reference genome, with peaks in mid-point frequency in nucleoid datasets taken to imply the presence of positioned MNase-resistant DNA protein complexes which we term: “chromatin particle positions”. Sequence data is then separated according to paired read end-to-end distances/insert size to directly reflect the extent of MNase protection of DNA by a specific DNA:protein complex and defining a “chromatin particle size”. In eukaryote experiments, sequence read pairs with an end-to-end distance of approximately 150bp effectively map positioned histone octamer nucleosomes (which are wrapped by 147bp of DNA). Here, the read pair mid-point positions effectively define hypernucleosomal dyad sequences of widely varying lengths (archaeal DNA:histone “slinkies” or “curly-fries”).

first: Fabian

last: Blombach

first: Finn

last: Werner


title: Next Generation Sequencing Quantitative Analysis of Wild Type, CDK8-/-, CDK19-/-, and CDK8-/-CDK19-/- mouse instestinal organoids transcriptomes

status: Public on Oct 23 2022

city: Montpellier

first: Daniel

last: Fisher

address: 1919 Route de Mende

department: IGMM

country: France

institute: CNRS

summary:
Purpose: The goals of this study were to compare gene expression profiles of mouse intestinal epithelium organoids with intact or disrupted CDK8 and CDK19 genes.
Methods: mRNA profiles of all organoid genotypes, in biological triplicates, were generated by deep sequencing using the BGISEQ SE50 50 million single-end, 50bp reads per sample. The sequence reads that passed quality filters were aligned to the mouse genome, quantified, and differential gene expression (DGE) analysis was performed using DEseq2.
Results: Using an optimized data analysis workflow, we mapped about 50 million sequence reads per sample to the mouse genome (GRCm38.p6) and identified differentially expressed genes.  This mild changes in overall gene expression, preferentially enriched in tissue specif genes. The transcription profile showed an overlap between those present in a CFTR KO context.
Conclusions: CDK8/19 knockout causes tissue specif expression alteration. Intestinal organoids presented a CFTR-like phenotype after removal of both genes

overall_design: Differential gene expression of RNAseq profiles of wild-type (WT) and wild Type, CDK8-/-, CDK19-/-, and CDK8-/-CDK19-/- mouse intestinal organoids. The effect of Senexin B as a CDK8/19 inhibitor on the transcriptome was also studied.

first: Susana

last: Prieto

first: Elsie

last: Hodimont

first: Lucie

last: Angevin

first: Geronimo

last: Dubra

first: Ana

middle: B

last: Aznar

first: Alain

last: Camasses

first: Christina

last: Begon-Pescia

first: Nelly

last: Pirot

first: François

last: Gerbe

first: Philippe

last: Jay

first: Liliana

last: Krasinska


title: Histone methylation mediates transgenerational modulations of sweet perception by high sugar diet [ChIP-Seq]

city: hangzhou

first: JIE

last: YANG

state: ZheJiang

address: Yuhangtang Road No.388,Zhejiang Province, Zijingang Campus of Zhejiang University, nano building 560 room

department: science life institute

institute: ZheJiang Univeristy

summary: The environment influences the metabolism and behavior of progeny by working through the germline to introduce spontaneous genetic mutations as well as a variety of epigenetic changes, including alterations in DNA methylation status, changes in non-coding RNAs (ncRNAs) and the post-translational modification of histones. Therefore, we used ChIP-seq to ask whether maternal HSD exposure induce alterations in post-translational modification of H3K27 and H3K9.

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for the histone modifications H3K27me3, H3K27ac, H3K79me2 and H3K9me3 in fly embryos which ancestors exposed in high sugar diet

first: Yang

last: Jie

first: Tang

last: Ruijun


title: Epigenome analysis of DU145 samples [II]

status: Public on Oct 31 2022

city: Guangzhou

first: Peng

last: Yuchong

address: The First Affiliated Hospital, Guangdong Pharmaceutical University, 19 Nonglinxia Road, Yuexiu District, Guangzhou, Guangdong, China

department: Clinical Pharmacy of the First Affiliated Hospital

institute: Guangdong Pharmaceutical University

type: Methylation profiling by genome tiling array

summary: The Illumina Infinium 850k Human DNA methylation BeadChip was used to obtain DNA methylation profiles in DU145 cell samples. Samples included normal, PLK1 knockdown and UHRF1 knockdown DU145 cell samples. Each sample is repeated three times.

overall_design: Bisulphite converted DNA from DU145 cell samples were hybridised to the Illumina Infinium 850k Human Methylation BeadChip.


title: Whole blood gene expression profiles associated with mortality in community-acquired pneumonia

status: Public on Oct 17 2022

city: Barcelona

first: Júlia

last: Perera-Bel

address: Doctor Aiguader, 88

department: MARData-BU

institute: Hospital del Mar Research Institute

summary: We aimed to examine the differences in the gene expression profile in peripheral blood at hospital admission between patients with community-acquired pneumonia (CAP) who died and survived during hospitalization. Whole blood samples for genome expression profile analysis were obtained within 24 hours of hospital admission. Gen set enrichment analysis (GSEA) identified gene sets positively enriched in the patients who survived, mainly related with interferon- alpha response, apoptosis, and sex hormones pathways. Similarly, GSEA identified gene sets positively enrichment for the patients who died (oxidative stress, endoplasmic reticulum stress, oxidative phosphorylation, and angiogenesis pathways).

overall_design: Multicenter, prospective, cohort study involving non-immunosuppressed adult patients requiring hospitalization for CAP. A total of 198 samples were analyzed

first: Diego

last: Viasus

first: Antonella

last: Simonetti

first: Lara

last: Nonell

first: Oscar

last: Marino

first: Yolanda

last: Meije

first: Lucía

last: Ortega

first: Montserrat

last: Sierra

first: Alexander

last: Rombauts

first: Gabriela

last: Abelenda-Alonso

first: Carlota

last: Gudiol

first: Magdalena

last: Arnal

first: Marta

last: Bódalo-Torruella

first: Jordi

last: Carratalà


title: Histone methylation mediates transgenerational modulations of sweet perception by high sugar diet

status: Public on Oct 19 2022

first: JIE

last: YANG

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


title: Epigenome of three deep-sea polychaete species

status: Public on Nov 06 2022

city: Montreal

first: Maeva

last: Perez

state: Qc

address: 1375 Avenue Thérèse-Lavoie-Roux

institute: Université de Montréal

summary: We provide the genome-wide methylome surveys of three species of deep-sea polychaete worms using Oxford Nanopore data: the siboglinids Paraescarpia echinospica and Ridgeia piscesae, and the alvinellid Paralvinella palmiformis. We characterised 5mCpG methylation in order to test hypotheses about the putative role of DNA methylation in these species.

sample_organism:
Ridgeia piscesae
Paralvinella palmiformis
Paraescarpia echinospica


title: Spatial transcriptomics data of GAN-KP tumor treated with regorafenib

status: Public on Oct 05 2022

city: Kumamoto City

first: Takashi

last: Semba

address: 2-2-1 Honjo, Chuo-ku

institute: International Research Center for Medical Sciences, Kumamoto University

summary: We conducted spatial transcriptomics data analysis of mouse tumors of gastric cancer treated with regorafenib, a multikinase inhibitor, which can suppress cancer-associated fibroblast growth by inhibiting platelet-derived growth factor receptor alpha and beta.

overall_design: Serially transplanted GAN-KP cells (S5) were subcutaneously inoculated into C57BL/6 mice. After 7 days, tumors were treated with vehicle control or regorafenib for 10 days. The mice were euthanized on day 21.

first: Takahiko

last: Akiyama

first: Tadahito

last: Yasuda

first: Tomoyuki

last: Uchihara

first: Takatsugu

last: Ishimoto


title: Neuronal activity stimulates astrocyte proliferation through NMDA receptor-dependent induction of Prostaglandin-Endoperoxide Synthase 2

status: Public on Nov 01 2022

city: South San Francisco

first: Josh

last: Kaminker

address: 1 DNA Way

department: Bioinformatics and Computational Biology

institute: Genentech

summary: Gene expression analysisis of NR2A and NR2B containing NMDA receptors after treatment with AP5, NVP-AAM077 and Ro25-6981

overall_design: 4 conditions, vehicle, AP5, Ro25, and NVP, 5 replicates of each sample

first: Joshua

middle: S

first: Yelin

last: Chen

first: Morgan

last: Sheng

first: Martin

last: Weber

first: Chaoying

last: Fu

first: Han

last: Lin

first: Hai

last: Ngu

first: Felix

last: Chu

first: Zora

last: Modrusan


title: Allelic effects on uromodulin aggregates drive autosomal dominant tubulointerstitial kidney disease

status: Public on Oct 02 2022

city: Zurich

first: Olivier

last: Devuyst

address: Winterthurerstrasse 190

department: Institute of Physiology

country: Switzerland

institute: University of Zurich

summary: Autosomal dominant tubulointerstitial kidney disease (ADTKD) caused by UMOD mutations is characterized by strong interfamilial variability. We generated two mutant Umod knock-in mouse models, harbouring two mutations associated with drastic differences in kidney survival in ADTKD patients. We performed bulk RNA-sequencing of kidney extracts from Umod KI mice at an early (1 month) and advanced (4 months) stage of disease.

overall_design: RNA-sequencing of mouse kidneys from Umod wild type and mutant mice (p.C171Y, p.R186S) at 1 and 4 months of age.

first: Guglielmo

last: Schiano

first: Jennifer

last: Lake

first: Marta

last: Mariniello


title: Machine learning for discovery: deciphering RNA splicing logic

status: Public on Oct 01 2022

city: New York

first: Oded

last: Regev

address: 215 Mercer St

institute: New York University

summary: Machine learning methods, particularly neural networks trained on large datasets, are transforming how scientists approach scientific discovery and experimental design. However, current state-of-the-art neural networks are limited by their uninterpretability: despite providing accurate predictions, they cannot describe how they arrived at their predictions. Here, using an ``interpretable-by-design'' approach, we present a neural network model that provides insights into RNA splicing, a fundamental process in the transfer of genomic information into functional biochemical products. Although we designed our model to emphasize interpretability, its predictive accuracy is on par with state-of-the-art models. To demonstrate the model's interpretability, we introduce a visualization that, for any given exon, allows us to trace and quantify the entire decision process from input sequence to output splicing prediction. Importantly, the model revealed novel components of the splicing logic, which we experimentally validated. This study highlights how interpretable machine learning can advance scientific discovery.

overall_design: Amplicon sequencing of input reporter sequences (associating exon sequences with barcodes) and output splicing products (cDNA from splicing assay used to quantify PSI).

first: Susan

last: Liao

first: Mukund

last: Sudarshan


title: Histone methylation mediates transgenerational modulations of sweet perception by high sugar diet [RNA-Seq]

status: Public on Oct 18 2022

first: JIE

last: YANG

summary: To investigate the differentially expressed gene in head of adult flies which ancestors exposed in high sugar diet

overall_design: Gene expression profiling analysis of RNA-seq data for the head of adult flies which ancestors exposed in high sugar diet

first: Yang

last: Jie


title: Germline piRNAs counteract endogenous retrovirus invasion from somatic cells- small RNA

status: Public on Sep 30 2022

city: CLERMONT-FERRAND

first: Emilie

last: BRASSET

address: 28 place Henri dunant

institute: CNRS 6293 INSERM U1103 Université Clermont Auvergne

type: Non-coding RNA profiling by high throughput sequencing

summary: In metazoan gonads, transposable elements (TEs) mobilization is limited by PIWI-interacting RNAs (piRNAs). These small RNAs originate from specific source loci, the piRNA clusters. piRNAs are known to silence TEs in the cells where they are produced. Endogenous retroviruses (ERVs), a subclass of TEs, pose a particular threat because they are capable of transiting from cell to cell. In this study, we reveal that piRNAs produced locally in germ cells counteract invasion by ERVs arriving from adjacent somatic cells. We reactivated the Drosophila ERV ZAM in somatic gonadal cells by deleting, using CRISPR-Cas9 genome editing, its single copy in the somatic flamenco piRNA cluster, while keeping the piRNA pathway fully functional. Upon reactivation, ZAM invaded the oocytes, resulting in transposition and severe fertility defects. We show that once ZAM-piRNAs are produced in germ cells they counter the invasion. Our study sheds new light on the mechanisms of recognition and regulation of invasive genetic elements, which is essential for the maintenance of genome integrity.

overall_design: small RNA sequencing

first: Marianne

last: Yoth

first: Nathalie

last: Guegen

first: Silke

last: Jensen

last: Brasset


title: Defining TCF1+ progenitor allogeneic CD8 T cell subset in acute graft-versus-host disease

status: Public on Oct 14 2022

city: Suwon-si

first: Se Jin

last: Im

state: Gyeonggi-do

address: 2066, Seobu-ro, Jangan-gu

department: Department of Immunology

institute: Sungkyunkwan University School of Medicine

summary: The goals of this study were to gain a better understanding of the heterogeneity and gene signatures of allogeneic PD-1+ CD8 T cells isolated from the spleen of GvHD B6 recipients of Balb/c T cells.

overall_design: PD-1+ CD8 T cells isolated from the spleen of GvHD B6 recipients of Balb/c T cells were isolated by Fluorescence-activated cell sorting (FACS) Aria II and analyzed using scRNA-seq.

first: Solhwi

last: Lee

first: Se


title: Germline piRNAs counteract endogenous retrovirus invasion from somatic cells - Total genomic DNA

overall_design: total genomic DNA purified with Qiagen Blood & Tissue Kit


title: TopBP1 associated with RNA in HEK293T cells

status: Public on Sep 23 2022

city: Tianjin

first: Zexing

last: Li

address: No.92 Weijin road

institute: Tianjin University

summary: We report the TopBP1 associated with RNA via using sequencing of RNA isolated by PAR-CLIP.

overall_design: Examination of  the potential RNA species that associates with TopBP1.

first: Xiaochun

last: Yu

first: Di

last: Xin


title: Circadian Clock-Controlled Translation of Specific mRNAs in Neurospora crassa Requires Rhythmic eIF2α Activity and P-body Sequestration [RNA-seq]

city: College Station

first: Deborah

last: Bell-Pedersen

state: Texas

address: 3258 TAMU

department: Biology

institute: Texas A&M University

summary: We report the genome-wide impact of rhythmic P-eIF2α levels in vivo by performing ribosome profiling and RNA-seq in Neurospora crassa samples grown over a circadian time course. We identified candidate genes which showed rhyhmic ribosome occupancy in WT cells but lost rhythms in mRNA levels and ribosome occupancy in the clock mutant Dfrq, eIF2α  kinase knockout Dcpc-3, and constitutively active kinase mutant cpc-3c cells. Select mRNAs harbor a P-body localization motif identified by MEME and MEME Suite's GOMo function. P-body localization of the target mRNAs provides an attractive mechanism for explaining translational rhythms from otherwise arrhythmic mRNAs.

overall_design: RNA-seq (done in parallel with ribosome profiling) of Neurospora crassa WT, clock mutant Dfrq, eIF2α  kinase knockout Dcpc-3, and constitutively active kinase mutant cpc-3c mycelia, grown over a circadian time course. Each time point has a duplicate.

first: Kathrina

last: Castillo

first: Cheng

last: Wu

first: Zhaolan

last: Ding

first: Matthew

last: Sachs


title: Circadian Clock-Controlled Translation of Specific mRNAs in Neurospora crassa Requires Rhythmic eIF2α Activity and P-body Sequestration [Ribo-seq]

overall_design: Ribosome profiling (ribo-seq) (done in parallel with RNA-seq) of Neurospora crassa WT, clock mutant Dfrq, eIF2α  kinase knockout Dcpc-3, and constitutively active kinase mutant cpc-3c mycelia, grown over a circadian time course. Each time point has a duplicate.


title: Circadian Clock-Controlled Translation of Specific mRNAs in Neurospora crassa Requires Rhythmic eIF2α Activity and P-body Sequestration

overall_design: Refer to individual Series


title: Small molecule inhibition of multiple RNA binding proteins underlies Musashi-2 independent phenotypes

status: Public on Sep 14 2022

city: Aurora

first: Neelanjan

last: Mukherjee

state: Colorado

address: Research Complex 1 South, 12801 E 17th Ave

department: Biochemistry and Molecular Genetics

institute: University of Colorado School of Medicine

summary: RNA binding proteins (RBPs) are key regulators of normal and pathological gene expression. Small molecules targeting RBP-RNA interactions are a rapidly emerging class of therapeutics. Ro-08-2750 (Ro) was previously identified as a competitive inhibitor of Musashi-RNA interactions. Here we show Ro potently inhibits steroidogenesis and viability independent of Musashi-2 in multiple cell lines. We identified Ro-interacting proteins using an unbiased proteome-wide approach. Other RBPs were a prominent class of Ro-interacting proteins and leveraging large-scale ENCODE data we found a subset of these phenocopy Ro inhibition. We provide a general framework for validating the specificity and identifying targets of RBP inhibitors in a cellular context.

overall_design: H295R cells were stimulated with 10nM AngII and treated with DMSO control or 5 uM Ro. Cells were harvested at 0, 4, 8, 12, 16, 24 hours post-stimulation. Additionally MUSASHI2 RIP-Seq was performed in unstimulated, untreated H295R cells to found RNAs bound by this RBP.

first: K

last: Walters

first: M

middle: P

last: Sajek

first: A

last: Issaian

last: Baldwin

first: E

last: Harrison

last: Murphy

last: Daniels

first: J

last: Haines

last: Hansen

last: D'Alessandro

first: N


title: Hybridization led to a rewired pluripotency network in Xenopus laevis [CUT&RUN]

city: Pittsburgh

first: Miler

middle: T

last: Lee

state: PA

address: 4249 Fifth Ave

department: Biological Sciences

institute: University of Pittsburgh

summary: After fertilization, maternally contributed factors to the egg initiate the transition to pluripotency, in large part by activating de novo transcription from the embryonic genome. Diverse mechanisms coordinate this transition across animals, suggesting that widespread evolutionary innovation has shaped the earliest stages of development. Here, we show that homologs of mammalian reprogramming factors OCT4 and SOX2 divergently regulate the two subgenomes of the allotetraploid Xenopus laevis, resulting in asymmetric activation of hundreds of homeologous gene pairs in the early embryo. Chromatin accessibility profiling and CUT&RUN for modified histones and transcription factor binding reveal extensive differences in enhancer architecture between the subgenomes, which likely arose after hybridization of X. laevis's diploid progenitors ~17 million years ago. However, comparison with diploid X. tropicalis shows broad conservation of embryonic gene expression levels when divergent homeolog contributions are combined, implying strong selection to maintain dosage in the pluripotency transcriptional program, amidst genomic instability following hybridization.

overall_design: Histone modification and transcription factor CUT&RUN was performed on Stage 8-10.5 embryos. Control samples were handled identically to CUT&RUN samples except without primary antibody addition.

first: Wesley

last: Phelps


title: Hybridization led to a rewired pluripotency network in Xenopus laevis [ATAC-seq]

overall_design: ATAC-seq was performed on animal caps from Stage 8-9 embryos.


title: Hybridization led to a rewired pluripotency network in Xenopus laevis [RNA-seq]

overall_design: RNA-seq with rRNA-depletion was performed on two embryos per sample from mixed clutches of 1-2 mothers. Embryos from the same collection are labeled with capital letters (A, B, etc.). Stage 10.5 samples had GFP, mCherry, and Luciferase mRNA added as a spike-in to rRNA-depleted RNA for an unrelated purpose. Samples excluded from analysis due to likely issue with cycloheximide treatment are labeled as DISCARDED.


title: Krüppel-like factors-4 and -2 are important regulators of joint tissue cells and protect against tissue destruction and inflammation in osteoarthritis [ChIP-seq]

status: Public on Sep 11 2022

city: La Jolla

first: Padma

last: Natarajan

state: CA

address: 10550 N.Torrey Pines Road

department: CCBB

institute: The Scripps Research Institute

summary: ChIP-seq with anti-HA tag antibody in TC28a2 cells transfected with HA-KLF4.We performed genome-wide analysis for KLF4-DNA association in TC28a2 human chondrocyte cells, to elucidate regulatory mechanisms of chondrogenic genes by KLF4.

overall_design: ChIP samples obtained from TC28a2 cells transfected with a vector expressing KLF4 and HA tag (HA-KLF4) were analyzed in duplicate. We also analyzed an IgG ChIP control obtainted from HA-KLF4 transfected cells, and a ChIP control sample with anti HA-tag antibody from empty vector-transfected cells.

first: Manabu

last: Kawata

first: Aishwarya

last: Sundaresan

first: Martin

last: Lotz


title: Istradefylline (KW6002) protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin anti-tumor effects [Kidney]

status: Public on Sep 12 2022

city: Lille

first: David

last: Blum

state: Cedex

address: 1 place de Verdun

department: Lille Neurosience & Cognition

institute: Inserm

summary: Cisplatin is a potent chemotherapeutic drug, widely used in the treatment of various solid cancers. However, its clinical effectiveness is strongly limited by frequent severe adverse effects, such as nephrotoxicity and chemotherapy-induced peripheral neuropathy. Therefore, there is an urgent medical need to identify novel strategies that would limit cisplatin-induced toxicity. In the present study, we provide evidence that the FDA-approved adenosine A2A receptor antagonist istradefylline (KW6002) significantly protects from cisplatin-induced nephrotoxicity and neuropathic pain in experimental models of acute and sub-chronic cisplatin intoxication. Importantly, we also demonstrate that the anti-tumoral properties of cisplatin were not altered by istradefylline in tumor-bearing mice and even potentiated at the molecular level. Altogether, the present results support the use of istradefylline as a new valuable preventive approach for the clinical management of patients undergoing cisplatin treatment.

overall_design: Animal procedures were performed in 8 to 10 weeks old male C57Bl6/J mice (Janvier Labs except for pain experiments, Jackson lab). Mice were fed a laboratory standard diet with water and food ad libitum and were kept under constant environmental conditions with a 12-hour light-dark cycle. Istradefylline (KW6002; Tocris) was dissolved in a carrier solution consisting in 15% DMSO, 15% cremophor (Sigma), 70% saline solution (vehicle). Cisplatin (Accord Healthcare) was dissolved in saline solution. Toxicity of sub-chronic cisplatin was evaluated following six daily i.p. injections of cisplatin (3 mg/kg) starting at day 0 and mice were sacrificed 72h after the last injection of cisplatin. KW6002 (3 mg/kg) was tested against sub-chronic cisplatin toxicity, the drug was administered daily i.p. from day -5 to day 7 (Supplementary Figure 1D).

first: Christelle

last: Cauffiez


title: Istradefylline (KW6002) protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin anti-tumor effects [Kidney_Tumor]

overall_design: LLC1 cells (Lewis Lung Cancer cells, ATCC® CRL-1642™) were cultured in DMEM with 10% foetal calf serum and penicillin-streptomycin. LLC1 cells (107) in PBS:matrigel (1:1, for a total volume of 100 µL) were subcutaneously injected in the right flank of animals. Tumors were measured twice a week with calipers and their volumes were estimated using the following equation: ½ (length x width2). When tumor volume reached 100 mm3, mice were randomly ascribed to the four experimental groups (Vehicle, KW6002, Cisplatin and Cisplatin/KW6002) as indicated in Supplementary Figure 1E.


title: Hybridization led to a rewired pluripotency network in the allotetraploid Xenopus laevis

status: Public on Sep 13 2022


title: Istradefylline (KW6002) protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin anti-tumor effects

status: Public on Sep 09 2022


title: Krüppel-like factors-4 and -2 are important regulators of joint tissue cells and protect against tissue destruction and inflammation in osteoarthritis


title: Krüppel-like factors-4 and -2 are important regulators of joint tissue cells and protect against tissue destruction and inflammation in osteoarthritis [DRUG-seq]

summary: We performed global gene expression analysis in Ad-KLF4-, Ad-EGFP- and non-transduced TC28a2 human chondrocyte cells, to study genes regulated by KLF4 comprehensively.

overall_design: RNA samples from Ad-KLF4-, Ad-EGFP- and non-transduced TC28a2 cells with and without IL-1β stimulation were obtained (N = 7 replicates per condition; 42 samples in total). Then, digital RNA with pertUrbation of Genes (DRUG-seq) analysis was performed.

first: Padmaja