title: NRF2-independent iron-triggered signaling via MAPK p38-ETS1 regulates LSEC Bmp6 mRNA expression [II]

status: Public on Jan 25 2024

city: Warsaw

first: Michal

last: Mikula

address: Roentgena 5

department: Experimental Oncology

country: Poland

institute: Maria Skłodowska-Curie National Research Institute of Oncology

summary: BMP6 is an iron-sensing cytokine produced by liver sinusoidal endothelial cells (LSECs). The transcription factor NRF2 was proposed to induce Bmp6 expression in response to iron-triggered oxidative stress, and NRF2 knock-out mice were shown not capable of regulating Bmp6 in response to massive diet-imposed iron overload. However, LSEC Bmp6 expression levels in the hemochromatosis mouse model reflect hepatocytic, not endothelial iron content. Hence, it is not fully resolved how iron signals translate into alterations of Bmp6 mRNA levels. To further explore the mechanisms of Bmp6 regulation, we employed female mice aged 10-11 months that are hallmarked by hepatocytic, but not LSEC iron accumulation and decreased transferrin saturation, hinting at the absence of systemic iron overload. We found that LSECs of aged mice exhibit increased Bmp6 levels as compared to young controls, but do not show oxidative stress or a transcriptional signature characteristic of activated NFR2-mediated signaling in FACS-sorted LSECs. We further observed that primary murine LSECs derived from both wild-type and NRF2 knock-out mice induce Bmp6 in response to acute iron exposure. By analyzing RNA sequencing data of FACS-sorted LSECs from aged versus young mice, as well as upon acute injections of iron citrate in young mice, we identified ETS1 as a candidate transcription factor involved in Bmp6 regulation. By conducting siRNA-mediated knock-down and small-molecule treatments in primary LSECs, we show that Bmp6 transcription is regulated in an NRF2-independent manner via ETS1, which is activated downstream of  p38 MAP kinase-mediated signaling. This knowledge expands the understanding of Bmp6 transcriptional control in both iron-triggered oxidative stress and under the conditions uncoupled to LSECs reactive oxygen species levels.

overall_design: We analyzed in total 7 versus 7 RNA samples derived from FAC-sorted LSECs obtained from young (8-10 weeks old) and aged (10-11 months old) female C57BL6J mice, respectively. The experiemnt was performed in two biological replicates (3 vs 3, and 4 vs 4).

first: Gabriela

last: Zurawska

first: Aneta

last: Jończy

first: Zuzanna

last: Sas

first: Izabela

last: Rumieńczyk

first: Maria

last: Kulecka

first: Katarzyna

last: Piwocka

first: Tomasz

last: Rygiel

first: Michał

last: Mleczko-Sanecka


title: Direct Reprogramming of Human Astrocytes into Spinal Cord Organoids Facilitating Spinal Cord Regeneration

status: Public on Feb 01 2024

city: shanghai

first: zhicheng

last: shao

address: dongan road 130

country: China

institute: fudan

type: Expression profiling by high throughput sequencing

summary: Human astrocytes have reported to reprogram into neurons, but they have yet to be induced to three-dimensional (3D) neural tissue for neural organogenesis. Here, we demonstrate a remarkable strategy for 3D organoid generation by direct reprogramming human astrocytes. By combining overexpression OCT4, suppression p53 and small molecules CHIR99021, SB431542, RepSox and Y27632, termed as Op53-CSBRY, we successfully reprogramed human astrocytes into neural ectodermal cells and further induced human 3D-brain organoid. Those organoids can be finally induced into spinal cord organoids by activating FGF, SHH and BMP signaling. The grafts of Human astrocyte derived spinal cord organoids (hADSC-Organs) can survived, differentiated into spinal cord neurons, migrated long distance, formed synaptic connectivity with host neurons, bridged complete injury spinal cord tissue in mice. This method indicates that human astrocytes could be directly triggered neural organogenesis, and may hold a great promising to support local astrocytes in situ organogenesis after brain damages, such as stroke and spinal cord injury.

overall_design: Screen of molecular conbined with factors to direct reprogramming astrocyte into neuron progenitors cell and therapy for spinal cord injuy.

first: Jinhong

last: Xu

first: Shi

last: Fang

first: Suixin

last: Deng

first: Xiaoning

last: Lin


title: NRF2-independent iron-triggered signaling via MAPK p38-ETS1 regulates LSEC Bmp6 mRNA expression [I]

overall_design: We analyzed in total 5 versus 5 RNA samples derived from FAC-sorted LSECs obtained from young female Balb/c mouse mice, intravenously injected with citrate buffer or iron-citrate solution (150 ug), respectively.


title: Biallelic non-productive enhancer-promoter interaction precedes imprinted expression of KcnK9 during mouse neural commitment

status: Public on Feb 05 2024

city: Clermont-Ferrand

first: franck

last: court

address: 28 Place Henri Dunant

country: France

institute: GReD CNRS

type: Genome binding/occupancy profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: 5-Hydroxymethylcytosine Profiling of Cell-Free DNA Identifies Bivalent Genes That Are Prognostic of Survival in High-Risk Neuroblastoma

city: Chicago

first: Mark

last: Applebaum

state: IL

address: 900 E 57th St

department: Pediatrics, Section of Hematology/Oncology

country: USA

institute: University of Chicago

summary:
Purpose: Neuroblastoma is the most common extracranial solid tumor in childhood. We previously showed that circulating cell-free DNA (cfDNA) and tumor biopsy derived 5-hydroxymethylcytosime (5-hmC) profiles identified patients with neuroblastoma who experienced subsequent relapse. Here, we hypothesized that 5-hmC modifications selectively enriched in cfDNA compared with tumor biopsy samples would identify epigenetic changes associated with aggressive tumor behavior and identify novel biomarkers of outcome in patients with high- risk neuroblastoma.

Methods: 5-hmC profiles from cfDNA (n = 64) and tumor biopsies (n = 48) were compared. Two neuroblastoma cell lines underwent chromatin immunopre- cipitation followed by sequencing (ChIP-Seq) for H3K27me3, H3K4me3, and H3K27ac; kethoxal-associated single-stranded DNA sequencing; hmC-Seal for 5-hmC; and RNA-sequencing (RNA-Seq). Genes enriched for both H3K27me3 and H3K4me3 in the included cell lines were defined as bivalent. Using bivalent genes defined in vitro, a bivalent signature was established in three publicly available cohorts of patients with neuroblastoma through gene set variation analysis. Differences between tumors with high or low bivalent signatures were assessed by the Kaplan-Meier method and Cox proportional hazards models.

Results: In cfDNA compared with tumor biopsy derived 5-hmC profiles, we found in- creased 5-hmC deposition on Polycomb Repressive Complex 2 target genes, a finding previously described in the context of bivalent genes. We identified 313 genes that bore bivalent chromatin marks, were enriched for mediators of neuronal differentiation, and were transcriptionally repressed across a panel of heterogeneous neuroblastoma cell lines. In three distinct clinical cohorts, low bivalent signature was significantly and independently associated with worse clinical outcome in patients with high-risk neuroblastoma.

Conclusion: Low expression of bivalent genes is a biomarker of worse outcome in patients with high-risk neuroblastoma.

overall_design: This SuperSeries is composed of the SubSeries listed below; refer to individual Series


title: Effect of depletion of ATG7 on gene expression in IAV-infected A549 cells

status: Public on Jan 11 2024

city: Fuzhou

first: JiLong

last: Chen

address: Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University

summary: To analyse differential expression genes（LncRNA and mRNA） in ATG7 knockdown cells and control cells upon influenza virus infection, transcriptome RNA sequencing was performed

overall_design: ATG7 knockdown cells and control cells were infected with PR8 influenza virus(MOI=0.5) for 16 hours .Comparative gene expression profiling analysis of RNA-seq data for ATG7 KD cells and control cells.

first: Biao

first: Yuhai

first: Ji-Long


title: Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA

status: Public on Jan 18 2024

city: New York

first: Jennifer

last: Warner-Schmidt

state: NY

address: 220 5th Ave 17th Floor

institute: Transcend Therapeutics

summary:
Background: Post-traumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder that can become chronic and debilitating when left untreated. Available pharmacotherapies are limited, take weeks to show modest benefit and remain ineffective for up to 40% of patients. Methylone is currently in clinical development for the treatment of PTSD. Preclinical studies show rapid, robust and long-lasting antidepressant-like and anxiolytic effects. The mechanism of action underlying these effects is not yet fully understood. This study investigated the downstream gene expression changes and signaling pathways affected by methylone in key brain areas linked to PTSD and MDD. It also sought to determine whether neuroplasticity-related genes were involved. We compared effects of methylone with MDMA to explore similarities and differences in their brain effects because MDMA-assisted psychotherapy has recently shown benefit in clinical trials for PTSD and methylone is a structural analog of MDMA.
Methods: We used RNA sequencing (RNA-seq) to probe drug-induced gene expression changes in the amygdala and frontal cortex, two brain areas responsible for emotional learning that are affected by PTSD and MDD. Rats were treated with methylone or MDMA (both 10 mg/kg, IP), and their responses were compared with controls.
Results: RNA-seq results revealed significant regulation of myelin-related genes in the amygdala, confirmed by immunohistochemistry. In the frontal cortex, methylone significantly upregulated genes implicated in neuroplasticity.
Conclusions: Results suggest that (1) methylone is a rapid-acting neuroplastogen that affects key brain substrates for PTSD and MDD and that (2) methylone appears to exhibit higher specificity and fewer off-target effects than MDMA. Together, these results are consistent with the reported clinical experiences of methylone and MDMA and bolster the potential use of methylone in the treatment of PTSD and, potentially, other neuropsychiatric disorders.

overall_design: Frontal cortex or amygdala were dissected from rats treated with methylone (10 mg/kg, IP), MDMA (10 mg/kg, IP) or vehicle and RNAseq was performed. There were six animals per treatment group. We compared gene expression in methylone or MDMA-treated animals with vehicle-treated controls.


title: Gene expression by RNA-seq in purified paneth cells in antibiotics microbiome depleded mice

status: Public on Dec 22 2023

city: Gent

first: Steven

last: Timmermans

address: Technologiepark 71

country: Belgium

institute: VIB-UGent

summary: The study of how gene expression in paneth cells changes after TNF admistration in mice were the microbiome has been depleted with broad spectrum antibiotics. The depletion of the microbiome excludes the occurence of indirect effects mediated through it by TNF on PC gene expression, only direct TNF effecs on crypt cells are measured

overall_design: To investigate the effects of TNF on PCs  without microbiome, PCs were purified from mice treated with antibiotics for 2 weeks and treated with 1µg/g TNF or PBS (control) by IP injection for 3 hours. A total of 4 biological replicates were used for each condition for a total of 8 samples

first: Charlotte

last: Wallaeys

first: Natalia

last: Garcia-Gonzalez

first: Jolien

last: Vandewalle

first: Tineke

last: Vanderhaeghen

first: Hester

last: Dufoo

first: Melanie

last: Eggermont

first: Riet

last: De Rycke

first: Serge

last: Verbanck

first: George

last: Kollias

first: Richard

middle: S

last: Blumberg

first: Takao

last: Iwawaki

first: Claude

last: Libert


title: NRF2-independent iron-triggered signaling via MAPK p38-ETS1 regulates LSEC Bmp6 mRNA expression

status: Public on Jan 24 2024

first: Michal

last: Mikula


title: Ago2-CLASH reveals a wide repertoire of small RNA mediated regulation

status: Public on Dec 24 2023

city: Brno

first: Vaclav

last: Hejret

address: Kamenice 5

country: Czech Republic

institute: Masaryk University


title: Ago2-CLASH reveals a wide repertoire of small RNA mediated regulation [RNA-Seq]

summary: Here we present the CLASH analysis of AGO2 in HEK293 cells to address the small RNA repertoire and uncover their physiological targets. We developed an optimized bioinformatics approach of chimeric read identification to detect chimeras of high confidence.  We report thousands of Ago2 target sites driven by microRNAs, but also a substantial number of Ago2 ‘drivers’ derived from fragments of other small RNAs such as tRNAs, snoRNAs, rRNAs and others. Target validation of several miRNAs delivered by 3’ Quantseq RNA-Seq.

overall_design: Comparative gene expression profiling analysis of RNA-seq data of antimir assays for miR-484, miR-92 and miR-320 to their wildtypes (each in 4 replicates)

first: Nandan

middle: M

last: Varadarajan

first: Eva

last: Klimentova

first: Katarina

last: Gresova

first: Ilektra-Chara

last: Giassa

first: Stepanka

last: Vanacova

first: Panagiotis

last: Alexiou


title: Gene expression by RNA-seq in purified paneth cells of WT and panetch cell specific  P55 KO mice 3 hours after TNF

status: Public on Dec 15 2023

first: Steven

last: Timmermans

summary: The study of how gene expression in paneth cells changes 3 hours after TNF admistration in mice were the TNFR1 (P55) genes was deleted in paneth cells using Defa6-cre.

overall_design: To investigate the effects of TNF on paneth cell gene expression trough direct signalling via TNFR1 (P55), an RNA-seq was performed 3 hours after TNF or PBS (control) injection in P55 KO mice and P55 WT littermates

first: Charlotte

last: Wallaeys

first: Natalia

last: Garcia-Gonzalez

first: Jolien

last: Vandewalle

first: Tineke

last: Vanderhaeghen


title: Transcriptomic response to Klotho deficiency in the renal distal convolution

city: Zurich

first: Ganesh

last: Pathare

state: Zürich

address: Winterthurerstrasse 190

department: Institute of Anatomy

country: Switzerland

institute: University of Zurich

summary: To assess the transcriptomic response to Klotho deficiency in the renal distal convolution (DC), we isolated DC cells from control and DC-specific Klotho KO mice using COPAS (Complex Object Parametric Analyzer and Sorter). Further comprehensive and unbiased RNA-seq identified altered transcripts associated with canonical MAPK pathway, as well as many novel targets of Klotho.

overall_design: We included 4 male mice in each control and KO group. The DC cells were isolated using COPAS. The transcriptomic repsonse was assesed by RNA-seq


title: Ago2-CLASH reveals a wide repertoire of small RNA mediated regulation [CLASH-seq]

overall_design: CLASH analysis of AGO2 in HEK293 cells in 3 replicates


title: Gene expression by RNA-seq in Liver of WT and panetch cell specific  P55 KO mice 18 hours after TNF

summary: After a challenge with TNF, gene expression changes in the liver may result from direct effect of TNF, through liver TNF receptors, and indirect effect. Baterial infiltration of the liver due to leaky gut after TNF is a primary contributor of this effect. In order to evaluate only the direct effects of TNF on lier transcriptome, we performed TNF challenge in normal WT mice and P55 panetch cell KO mice, which do not show the leaky gut syndrome.

overall_design: To investigate the direct effects of TNF on liver gene expression, an RNA-seq was performed 18 hours after TNF or PBS (control) injection in P55 KO mice and P55 WT littermates (4 mice/group except KO+PBS: 3 mice/group)

first: Hester

last: Dufoo

first: Melanie

last: Eggermont

first: Riet

last: De Rycke

first: Serge

last: Verbanck

first: George

last: Kollias

first: Richard

last: Blumberg


title: shRNA-based miRNA overexpression results in significant off-target effects caused by isomiR production [DU-145 cells]

status: Public on Nov 17 2023

city: Moscow

first: Anton

last: Zhiyanov

address: 20 Myasnitskaya ulitsa

department: Faculty of Biology and Biotechnology

country: Russia

institute: HSE University

type: Non-coding RNA profiling by high throughput sequencing

summary: miRNA overexpression strategy based on RNA Polymerase (Pol) III mediated expression of short hairpin RNA (shRNA) coding particular miRNA is widely used for miRNA functional studies. For some miRNAs, e.g., encoded in the genome as a part of a polycistronic miRNA cluster, it is most likely the only way for their individual stable overexpression. Here we have revealed that extra \texttt{U} residues (up to five) added Pol III at the 3$'$-end of the transcribed shRNA associated with a shift in the Dicer cleavage position of the shRNA. This results in the undesirable formation of 5$'$-end miRNA isoforms (5$'$-isomiRs), which have a significantly altered seed region compared to the initially encoded canonical hsa-miR-93-5p. The predominant expression of 5$'$-isomiRs without three or four first nucleotides instead of the canonical isoform could be disclosed based on miRNA-Seq analysis. Moreover, mRNA sequencing data showed that the 5$'$-isomiRs of hsa-miR-93-5p presumably regulate their own mRNA targets. Thus, omitting miRNA-Seq analysis may lead to erroneous conclusions regarding revealed mRNA targets and possible molecular mechanisms in which studied miRNA is involved.

overall_design:
DU-145 (prostate cancer) cell line was transduced by lentiviral particles coding one of the three types of shRNA to achieve stable overexpression of hsa-miR-93-5p.
All shRNA constructs contained the sequence of the canonical hsa-miR-93-5p and differed in their loop sequence only (5'-CUACCUGCACGAACAGCACUUUG-3' -- upper stem; 5'-CUCGAG-3', 5'-UUCAAGAGA-3', 5'-UUCUAAAA-3' -- stem loops; 3'-...UUGAUGGACGUGCUUGUCGUGAAAC-5' -- lower stem).
To comprehensively understand the overexpressed isoforms of hsa-miR-93-5p and their impact on the cellular transcriptome profile, we conducted sequencing of both miRNAs (3 repeats for the control, 3 repeats for the first loop and 2 repeats for other ones) and mRNAs (3 repeats for control and all loops).

first: Diana

last: Maltseva

first: Ivan

last: Kirillov

first: Daria

last: Averinskaya

first: Roman

last: Suvorov

last: Gubani

first: Anna

last: Kudriaeva

first: Alexey

last: Belogurov

first: Alexander

last: Tonevitsky


title: A longitudinal single-cell atlas of treatment response in pediatric AML (scRNA-Seq)

status: Public on Nov 20 2023

city: Vancouver

first: Marco

last: Marra

state: BC

address: 675 West 10th Avenue

department: Genome Sciences Centre

country: Canada

institute: BC Cancer Research Centre

summary: Pediatric acute myeloid leukemia (pAML) is a disease characterized by heterogeneous cellular composition, driver alterations and prognosis. Characterization of this heterogeneity and how it affects treatment response remains relatively understudied in pediatric patients. We therefore used single-cell RNA sequencing and single-cell ATAC sequencing to profile 684,031 diagnosis, remission and relapse cells from 28 patients representing different pAML subtypes. Analysis revealed that at diagnosis, cellular compositions differed between distinct subgroups. Upon relapse, cellular hierarchies transitioned towards a more primitive state regardless of subtype. These primitive cells were distinct compared to cells at diagnosis, having underrepresentation of transcriptional programs involved in myeloid differentiation while programs commonly found in other lineages were overrepresented. In a subset of patients, this appeared to accompany the appearance of a B-lymphoid-like hierarchy. Together, our data reveal the emergence of apparent subtype-specific plasticity upon treatment and inform on potential novel therapeutic angles to target these cell populations.

overall_design:
Single cell RNA sequencing  from 28 matched patient tumors enrolled in the study. Biopsies were taken from bone marrow or peripheral blood at diagnosis, remission and relapse and Ficoll-enriched.
-----------------------------------
Authors state:
Raw data have not been uploaded as it concerns sequencing data from patients. These data are in the process of being uploaded to the protected environment of EGA under accession number EGAS00001007323.

first: Sander

last: Lambo

first: Diane

middle: L

last: Trinh

first: Rhonda

middle: E

last: Ries

first: Dan

last: Jin

first: Audi

last: Setiadi

first: Michelle

last: Ng

first: Veronique

middle: G

last: Leblanc

first: Mike

last: Loken

first: Lisa

last: Broderson

first: Fangyan

last: Dai

first: Laura

last: Pardo

first: Xiaotu

last: Ma

first: Suzanne

last: Vercauteren

first: Soheil

last: Meschinchi

middle: A


title: Single cell analyses reveal the transient emergence of retinal progenitor cells in the ciliary margin zone during human retinal development

status: Public on Nov 29 2023

city: Newcastle Upon Tyne

first: Majlinda

last: Lako

address: International Centre for Life, Central Parkway

department: Institute of Genetic Medicine and Institute for Ageing

country: United Kingdom

institute: Newcastle University


title: scRNAseq of bone marrow (BM) T cells and hematopoietic stem and progenitor cells (HSPCs) of acute myeloid leukemia patients post allogeneic stem cell transplantation (alloSCT).

city: Heidelberg

first: Anna

last: Mathioudaki

state: None / N/A

address: Meyerhofstraße 1, 1

country: Germany

institute: EMBL Heidelberg

summary: Gene expression profile at single cell level of bone marrow (BM) T cells and hematopoietic stem and progenitor cells (HSPCs) of acute myeloid leukemia patients post allogeneic stem cell transplantation (alloSCT) of patients in complete remission (CR) and relapse (REL).

overall_design:
HSPCs and T cells were isolated using Fluorescence-activated cell sorting (FACS) according to the presence of CD34 and CD3 respectively, and were then analyzed using scRNAseq. Cells from all samples per group were pooled in one 10x reaction.

UPDATES:
[Mar-08-2026] The title, disease state, and processed data file names for Sample GSM6660161 were renamed from "CR" to "REL", and the title, disease state, and processed data file names for Sample GSM6660162 were renamed from "REL" to "CR". The processed data files associated with each GSM did not change.

first: Xizhe

last: Wang

first: Judith

last: Zaugg

first: Caroline

last: Pabst


title: Single cell analyses reveal the transient emergence of retinal progenitor cells in the ciliary margin zone during human retinal development [scRNA-seq]

summary: Retina is the innermost, light-sensitive layer that lines the back of the eye and is vital for light sensing and image processing. All the retinal cells types are derived from retinal progenitor cells (RPCs) in an orderly spatio-temporal manner that has been well studied in vertebrates. To better understand the emergence of RPCs, their localisation and differentiation to retinal lineages, we performed single cell (sc) RNA-Seq of 24 samples spanning 13 time points from 10-21 post-conception weeks of human development. Several types of progenitors were identified, including early and late RPCs which in turn gave rise the transient neurogenic progenitors that differentiated to all retinal neurones. Spatial transcriptomic analyses combined with scRNA-Seq revealed localisation of early RPCs in the ciliary margin of developing human retinas up to 10 PCW of development and propagation of neural retina differentiation from the centre to the periphery. Single cell ATAC-Seq analyses of 11 samples spanning 8-21 PCW of human development identified Hippo-Yap signalling as key pathway regulating RPC proliferation and cell cycle exit. These results provide the molecular map of human retinal development which may help guide generation of RPCs from human pluripotent stem cells and the design of cell-based replacement therapies for treating retinal dystrophies

overall_design: 24 samples of developing human eyes neural retina from 7.5-21 post-conception weeks

first: Birthe

last: Dorgau

first: Joseph

last: Collin

first: Agata

last: Rozanska

first: Darin

last: Zerti

first: Moira

last: Crosier

first: Rafiqul

last: Hussain

first: Jonathan

last: Coxhead

first: Tamilvendhan

last: Dhanaseelan

first: Jane

last: Sowden

first: David

last: Fitzpatrick

first: Rachel

last: Queen


title: Dynamic changes of macrophage polarization during Salmonella infection in zebrafish

city: Montpellier

first: Mai-Eva

last: Nguyen-chi

address: Pl. Eugène Bataillon

institute: CNRS

summary:
To investigate the polarization status of macrophages during salmonella persistent infection we established a model of Salmonella enterica serovar Thyphimurium infection in the zebrafish larva in which salmonella survive long term inside the host. In this model, during initial stages of the infection, macrophages are recruited to the infection site and express tnfa. By contrast, in the late stages of the infection, macrophages form clusters at the infection site and do not express tnfa.
The objective is to characterize the transcriptional profile of macrophages in early stage of infection (4 hours post-infection) and late stage of infection (4 days post-infection).

overall_design: Comparative gene expression profiling analysis of RNA-seq data for macrophages from Salmonella infected larvae at 4 hours post-infection (4 replicates) and 4 days post-infection (4 replicates). Controls are macrophages from non-infected larvae at 4 hours post-infection (4 replicates) and 4 days post-infection (3 replicates).

first: Jade

last: Leiba

first: Christina

last: Begon-Pescia

first: Mai

last: Nguyen-Chi


title: Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and PS micro-/nanoplastics stressed E. coli K-12 LE392, P. putida KT2440, and RP4 plasmid Transcriptomes

status: Public on Dec 05 2023

city: Shenzhen

first: Yuanyuan

last: Kang

address: No. 6 Pingshan 1st Road, Taoyuan Street, Nanshan District

department: School of Civil and Environmental Engineering

institute: Harbin Institue of Technology

summary: The goals of this study are to use Next-generation sequencing (NGS) to detect bacterial mRNA profiles of wild-type E. coli K-12 LE392, E. coli BL21 (DE3), P. putida KT2440 and IncPα RP4 plasmid, and their mRNA response under the exposure of different sizes of Polystyrene (PS), including 20 nm, 120 nm and 1 μm. The concentrations were 0.1, 10 mg/L for every size of PS. The group without adding PS was the control group. Each concentration was conducted in triplicate. By comparing the mRNA profiles of experimental groups and control group, the effects of these 3 sizes of PS on transcriptional levels can be revealed. Illumina HiSeq PE150 was applied. NEBNextő Ultra II Directional RNA Library Prep Kit for Illumina was used for library construction. Then, the sequence reads consisting of at least 85% bases were progressively trimmed at the 3’-ends until a quality value ≥ 20 were kept. Downstream analyses were performed using the generated clean reads of no shorter than 75 bp. The clean reads of each sample were aligned to the E. coli reference genome (NC_000913), P.putida reference genome (NC_002947), and IncPα plasmid reference genome (L27758) using Bowtie2. RSeQC was used to calculate the strand-specific coverage for each gene, and to analyze the differential expression in triplicate bacterial cell cultures. The statistical analyses and visualization were conducted using CummeRbund package in R (http://compbio.mit.edu/cummeRbund/). Gene expression was calculated as fragments per kilobase of a gene per million mapped reads (FPKM, a normalized value generated from the frequency of detection and the length of a given gene.

sample_organism:
Pseudomonas putida
Escherichia coli

platform_organism:
Pseudomonas putida
Escherichia coli

overall_design: Bacterial mRNA profiles of wild-type E. coli K-12 LE392, E. coli BL21 (DE3), P. putida KT2440, and IncPα RP4 plasmid in response to 0.1 mg/L 20 nm PS, 10 mg/L 20 nm PS, 0.1 mg/L 120 nm PS, 10 mg/L 120 nm PS, 0.1 mg/L 1 μm PS, and 10 mg/L 1 μm PS for 2 hours, bacteria and plasmid without adding PS are the control group, in triplicate, using Illumina HiSeq PE150.

first: Yue

last: Wang

first: Jianhua

last: Guo

first: Jianqiang

last: Su

first: Aijie

first: Shu-Hong

last: Gao


title: Single-cell Transcriptome Analysis Reveals the Dynamic Populations of Vascular Cells in Neointimal Hyperplasia

status: Public on Nov 14 2023

city: Shanghai

first: Guangzheng

last: Shi

address: No. 197, Ruijin Second Road

department: Ruijin Hospital

institute: Shanghai Jiao Tong University School of Medicine

summary: Neointimal hyperplasia (NIH) are the major causes of re-stenosis in coronary intervention. Fibroblasts, vascular smooth muscle cells and endothelial cells are the main disease-causing cells in NIH. However, Yet how these cells contribute to the pathophysiology of NIH remains elusive. This study was aimed at gaining new insights into the heterogeneity of these cells by using single-cell RNA sequencing and up-to-date analytical method.

overall_design: Carotid artery of each experimental group were harvested from both mice after 2 weeks postoperatively (six mice per sample and one sampple per group). Vessles were enzymatically digested to single-cell suspension, and then scRNA-seq libraries were built with the 10x Genomics platform.

first: Qun

last: Li


title: A longitudinal single-cell atlas of treatment response in pediatric AML (scATAC-Seq)

first: Marco

last: Marra

overall_design:
Single cell ATAC sequencing from 28 matched patient tumors enrolled in the study. Biopsies were taken from bone marrow or peripheral blood at diagnosis, remission and relapse and Ficoll-enriched.
-----------------------------------
Authors state:
Raw data have not been uploaded as it concerns sequencing data from patients. These data are in the process of being uploaded to the protected environment of EGA under accession number EGAS00001007323.

first: Sander

last: Lambo

first: Diane

last: Trinh

first: Rhonda

last: Ries

first: Dan

last: Jin

first: Audi

last: Setiadi

first: Michelle

last: Ng

first: Veronique

last: Leblanc

first: Mike

last: Loken

first: Lisa

last: Broderson

first: Fangyan

last: Dai

first: Laura

last: Pardo

first: Xiaotu

last: Ma

first: Suzanne

last: Vercauteren

first: Soheil

last: Meschinchi


title: CRIPSR screen identified CLEC16A suppresses astrocyte inflammasome-involved pathology via mitophagy: human in vitro study

status: Public on Nov 09 2023

city: Boston

first: Zhaorong

address: 60 Fenwood Road

institute: Dana Farber Cancer Institute

summary: CLEC16A knocked down human embryonic stem cell (hESC) derived astrocytes

overall_design: 23 samples of hESC astrocytes collected after  CLEC16A shRNA knockdown and TNFα/IL-1β stimulation.

first: Atsushi

last: Kadowaki

first: Francisco

middle: J

last: Quintana


title: A Massively Parallel Screen of 5′UTR Mutations Identifies Variants Impacting Translation and Protein Production in Neurodevelopmental Disorder Genes

status: Public on Nov 08 2023

city: St. Louis

first: Joseph

middle: D

last: Dougherty

state: MO

address: 4370 Duncan Ave

department: Genetics

institute: Washington University in St. Louis

summary: De novo mutations cause a variety of neurodevelopmental disorders including autism. Recent whole genome sequencing has identified hundreds of mutations in untranslated regions (UTRs) of genes from individuals with autism, but it is impossible to predict from sequence alone which are functional, and thus might be causal.  Therefore, we developed a high throughput assay to screen the consequence over 1,000 variants from 5'UTRs mutations on transcript abundance and translation efficiency. This assay successfully enriched for elements that alter reporter translation, identifying over 100 potentially functional mutations.  Studies in patient-derived cell lines further confirmed these mutations alter protein production in individuals in autism, including for multiple genes known to cause of syndromic forms autism, suggesting a diagnosis for these individual patients. Since UTR function varies by cell type, we further optimized this high throughput assay to enable assessment of mutations in neurons of the living brain.  Neurons demonstrate profoundly different principles of regulation by 5'UTRs, consistent with more robust mechanism for reducing impact of 5'UTR RNA structure. Overall our results highlight a new approach for assessing the impact of 5’UTR across cell types and suggest some cases of neurodevelopmental disorder may be caused by such variants.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Pooled library screens of synthetic reporter genes containing variable 5' UTR sequences and associated barcode sequences in the 3'UTR were performed either in HEK cells or in mouse brain in vivo in order to measure the effects of 5'UTR elements and their variants on transcript abundance and translation efficiency. HEK cells were transfected with a plasmid library containing approximately 33,000 uniquely barcoded reporters, and in vivo experiments were performed by transcranial delivery of AAV-packaged sub-libraries each containing a third of the total library. RNA and DNA were extracted from each sample, and RNA was subjected to density centrifugation and fraction to isolate mRNA associated with the 43S preinitation complex, monosomes, or polysomes. The barcode-containing 3'UTRs were amplified from each fraction to determine the abundance of each respective 5'UTR-associated reporter. All in vivo mouse experiments were performed in a Vglut2-Cre line so that a LoxP-flanked cassette in the 3'UTR is inverted only in glutamatergic neurons. For each in vivo RNA sample, two reverse transcription primers, one specific to the unrecombined state ("CreOFF") and one specific to the inverted state ("CreON"), were used to prepare libraries to esimtate the reporter abundance in both Cre-expressing glutamatergic neurons and non-Cre-expressing cells. For both HEK and in vivo experiments, six biological replicates were collected.

first: Stephen

middle: P

last: Plassmeyer

first: Colin

last: Florian

first: Michael

last: Kasper

first: Rebecca

last: Chase

first: Shayna

last: Mueller

first: Kelli

last: McFarland White

first: Courtney

middle: F

last: Jungers

first: Slavica

last: Pavlovic Djuranovic

first: Sergei

last: Djuranovic


title: CRISPR screen identified CLEC16A suppresses astrocyte inflammasome-involved pathology via mitophagy: EAE study

last: Li

summary: CLEC16A conditional knockout using GFAP-Cre

overall_design: 12 samples of astrocytes and 12 samples of microglia sorted from EAE mice (day 30)


title: Thapsigargin inhibition of coronavirus PHEV replication by Ca2+ mediated metabolic reprogramming

status: Public on Nov 10 2023

city: changchun

first: junchao

last: Shi

state: jilin

address: xi'an road

department: College of Veterinary Medicine

institute: Jilin University

summary: The coronaviruses (CoVs) represent a large family of human and animal pathogens that cause significant health and economic burdens worldwide. Porcine hemagglutinating encephalomyelitis virus (PHEV), belonging to the genus Betacoronavirus, is one of the six coronaviruses that infect pigs, for which no effective drug or vaccine is commercially available. Here, we found that thapsigargin (Tg), an ER stress inducer, potently blocks PHEV replication in non-cytotoxic levels and the antiviral effect is long-lasting at least 60 h post-Tg exposure in different cells. Time-of-addition assay demonstrated that Tg significantly inhibit PHEV replication in N2a cells when treated immediately before, during, or after virus infection. Tg does not directly interact with PHEV particles and transcriptome analysis reveals a unique antiviral mechanism of Tg through Ca2+ mediated metabolic reprogramming. Crucially, oral administration of Tg prolong the survival time and reduced virus titres in the brains of treated mice. Besides, Tg also exerts a profound antiviral effect on alphacoronavirus, deltacoronavirus, rhabdoviruses, parapoxvirus and picornavirus. Taken together, Tg exerts antiviral effects by targeting host factors shared by different viruses, suggesting that this compound (or derivatives thereof) may be developed into broad-spectrum antiviral drugs without considering the drug resistance caused by virus mutation.

overall_design:
To investigate the antiviral potential and target of Thapsigargin, mock or PHEV-infected N2a cells were treated with Thapsigargin or DMSO.
We then performed gene expression profiling analysis using data obtained from RNA-seq of 4 different treatment groups at 24 h.
Comparative gene expression profiling analysis of RNA-seq data for DMSO-treated (M), Thapsigargin-treated (T), PHEV-infected (P) , PHEV-infected and Thapsigargin-treated (PT) N2a cells.

first: Junchao

first: Qianhan

last: Jia

first: Zi

first: Wenqi

last: He


title: ASCL1 induces neurogenesis in human Muller glia

status: Public on Oct 30 2023

city: Seattle

first: Thomas

last: Reh

state: Washington

address: 1959 NE Pacific Street, UW School of Medicine, Seattle, WA 98195

department: Department of Neurobiology and Biophysics

institute: University of Washington

summary: In mammals, loss of retinal cells due to disease or trauma is an irreversible process which can lead to blindness. Interestingly, regeneration of retinal neurons is a well-established process in some non-mammalian vertebrates and is driven by the Muller glia (MG), which are able to re-enter the cell cycle and reprogram into neurogenic progenitors upon retinal injury or disease. Progress has been made to restore this mechanism in mammals to promote retinal regeneration: MG can be stimulated to generate new neurons in vivo in the adult mouse retina after the over-expression of the pro-neural transcription factor Ascl1. In this study, we applied the same strategy to reprogram human MG derived from fetal retina and retinal organoids into neurons. Combining scRNA-seq, scATAC-seq, Immunofluorescence, and electrophysiology we demonstrate that human MG can be reprogrammed into neurogenic cells in vitro.

overall_design: To study the development of the Muller glial cell over time in the human retina, fetal retinal tissues from a D59 and D76 samples were processed with the Multiome kit (snRNA-seq and snATAC-seq). For the D76 sample, the central part of the retina was isolated from the periphery and samples were further processed individually. We also include in this submission scRNA-seq data from the over expression of ASCL1 in human fetal Muller glia cultures. For the reprogramming paradigme we used Muller glia in vitro cultures derived from Retinal organoids and Retinospheres were generated. Cultures were then infected with a lentivirus driving the expression of the pro-neural transcription factor ASCL1 prior to processing with the 10x genomics platform.

first: Juliette

last: Wohlschegel

first: Connor

last: Finkbeiner

first: Dawn

last: Hoffer

first: Faith

last: Kierney

first: Aric

last: Prieve

first: Isabel

last: Ortuno-Lizaran

first: Alexandria

last: Murry

first: Alex

middle: K

last: Haugan

first: Fred

last: Rieke

first: Sam

last: Golden


title: CLEC16A in astrocytes promotes mitophagy and limits pathology in a multiple sclerosis mouse model [bulk RNA-Seq]

first: Zhaorong

summary:
Astrocytes promote neuroinflammation and neurodegeneration in multiple sclerosis (MS) through cell-intrinsic activities and their ability to recruit and activate other cell types. Here, in a genome-wide CRISPR-based forward genetic screen investigating regulators of astrocyte proinflammatory responses, we identified the C-type lectin domain-containing 16A gene (CLEC16A), linked to MS susceptibility, as a suppressor of nuclear factor-κB (NF-κB) signaling. Gene and small-molecule perturbation studies in mouse primary and human embryonic stem cell-derived astrocytes in combination with mitochodrial, metabolic and multiomic analyses established that CLEC16A promotes mitophagy, limiting mitochondrial dysfunction and the accumulation of mitochondrial products that activate NF-κB, the NLRP3 inflammasome and gasdermin D. Astrocyte-specific Clec16a inactivation increased NF-κB, NLRP3 and gasdermin D activation in vivo, worsening experimental autoimmune encephalomyelitis, a mouse model of MS. Moreover, we detected disrupted mitophagic capacity and gasdermin D activation in astrocytes in samples from individuals with MS. These findings identify CLEC16A as a suppressor of astrocyte pathological responses and a candidate therapeutic target in MS.
Scheduled for publication in Nature Neuroscience
DOI: 10.1038/s41593-025-01875-9

overall_design: Refer to individual Series


title: Epigenomic Profile of Lineage-Traced Mouse Horizontal Basal Cells Before and 24 Hours After Injury

city: Bethesda

first: Whitney

last: Heavner

state: MD

address: Building 35 Rm 2B-203

department: NINDS

institute: National Institutes of Health

summary: Wild-type horizontal basal cells (HBCs) from mouse olfactory epithelium were profiled using single-cell ATAC-seq (10x Genomics v2) to identify regions of accessible chromatin in individual cells before and 24 hours after acute injury.

overall_design: 24 hours after injury by intraperitoneal injection of methimazole, Krt5-CreER^T2; Rosa26-LSL-YFP/YFP lineage-traced cells were purified via fluorescence activated cell sorting (FACS). Uninjured YFP+ cells were also collected. Three biological replicates per condition (uninjured and 24 hours post-injury) were collected.

first: Hsin-Jung

last: Chou

first: John

last: Ngai

first: Koen

last: Van den Berge


title: Deficiency of the Heterogeneous Nuclear Ribonucleoprotein U locus leads to delayed hindbrain neurogenesis

status: Public on Oct 02 2023

city: Solna

first: Kristiina

last: Tammimies

address: Visiongatan 4

department: Department of Women's and Children's Health

country: Sweden

institute: Karolinska Institutet

summary: Genetic variants affecting Heterogeneous Nuclear Ribonucleoprotein U (HNRNPU) have been identified in several neurodevelopmental disorders (NDDs). HNRNPU is widely expressed in the human brain and shows the highest postnatal expression in the cerebellum. Recent studies have investigated the role of HNRNPU in cerebral cortical development, but the effects of HNRNPU deficiency on cerebellar development remain unknown. Here, we describe the molecular and cellular outcomes of HNRNPU locus deficiency during in vitro neural differentiation of patient-derived and isogenic neuroepithelial stem cells with a hindbrain profile. We demonstrate that HNRNPU deficiency leads to chromatin remodeling of A/B compartments, and transcriptional rewiring, partly by impacting exon inclusion during mRNA processing. Genomic regions affected by the chromatin restructuring and host genes of exon usage differences show a strong enrichment for genes implicated in epilepsies, intellectual disability, and autism. Lastly, we show that at the cellular level. HNRNPU downregulation leads to altered neurogenesis and an increased fraction of neural progenitors in the maturing neuronal population. We conclude that, HNRNPU locus is involved in delayed commitment of neural progenitors to neuronal maturation in cell types with hindbrain profile.

overall_design: Two different HNRNPU locus deficient hindbrain neuronal culture models were compared with control samples (3-5 technical replicates). ***The submitters are not legally permitted to submit the raw data to GEO or a restricted-access database such as dbGaP or EGA. Therefore, raw data is not provided.

first: Francesca

last: Mastropasqua

first: Marika

last: Oksanen

first: Cristina

last: Soldini

first: Shemim

last: Alatar

first: Abishek

last: Arora

first: Roberto

last: Ballarino

first: Maya

last: Molinari

first: Federico

last: Agostini

first: Axel

last: Poulet

first: Michelle

last: Watts

first: Ielyzaveta

last: Rabkina

first: Martin

last: Becker

first: Danyang

last: Li

first: Britt-Marie

last: Anderlid

first: Johan

last: Isaksson

first: Karl

last: Lundin Remnelius

first: Mohsen

last: Moslem

first: Yannick

last: Jacob

first: Anna

last: Falk

first: Nicola

last: Crosetto

first: Magda

last: Bienko

first: Emanuela

last: Santini

first: Anders

last: Borgkvist

first: Sven

last: Bölte


title: Effect of PCIF1 knockdown on gene exppression in HeLa S3 cells

status: Public on Sep 30 2023

city: Toyama

first: Yutaka

last: Hirose

state: Toyama

address: 2630 Sugitani

department: Graduate School of Medicine and Pharmaceutical Sciences

country: Japan

institute: University of Toyama

summary:
We previously identified PCIF1 (Phosphorylated CTD Interacting Factor 1) as a novel phosphorylated C-terminal domain (CTD) of RNA polymerase II. We also recently identified PCIF1 as a new cap-specific adenine N6 methyltransferase (CAPAM) responsible for creating N6, 2’-O-dimethyladenosine (m6Am) at the 5’-end of mRNAs. However, it remains unclear how PCIF1 regulates gene expression.
To identify genes whose expression levels are affected by PCIF1 knockdown in human cultured cells, we performed gene expression profiling by microarray analysis.

overall_design: HeLa S3 cells were seeded on 6-well plates at 1.0 × 105 cell/well and cultured at 37°C 24 h before transfection. Cells were transfected with either negative control siRNA or siRNA specific to human PCIF1 gene using Lipofectamine RNAi MAX (ThermoFisher) and further cultured for 72 h at 37°C.

first: Hiroyasu

last: Ishiguro

first: Ai

last: Sugita

first: Natsuki

last: Yanagisawa

first: Yoshiaki

last: Ohkuma

last: Tabuchi


title: Transcriptional profiling of male PAB rats with compensated and decompensated right ventricule

status: Public on Sep 29 2023

city: Bad Nauheim

first: Fatemeh

last: Khassafi

address: Parkstrasse

institute: Max Planck Institute

summary: We performed molecular phenotyping of adaptive to maladaptive RV hypertrophy remodeling, using transcriptome analysis of RV tissue obtained from PAB rats. This data along with other datasets linked within this study, provides a resource to comprehensively compare human RV remodeling to the animal RV dysfunction models (PAB) and led to the validation of state-specific biomarkers and potential therapeutic targets for RV dysfunction.

overall_design: RNA sequencing was performed for RV tissues obtained from PAB rats which were characterized as compensated RV, decompensated RV by hemodynamics, as well as normal RV from control rats, including only male samples as follows: control (n=5), compensated RV (n=5), decompensated RV (n=4)

first: Prakash

last: Chelladurai

first: Sébastien

last: Bonnet

first: Soni

last: Pullamsetti


title: Extensive Crosstalk between BMP and Notch Signaling Pathways in Activated Adult Muscle Stem Cells [RNA-seq I]

status: Public on Oct 01 2023

city: Berlin

first: Markus

last: Schuelke

state: Berlin

address: Augustenburger Platz 1

department: Neuropediatrics

institute: Charite

summary: Muscle stem cells (MuSC) are the cellular source for generation and regeneration of skeletal muscle. To ensure correct muscle growth, MuSC self-renewal and differentiation need to be tightly regulated. Several signaling systems have been implicated in the control of MuSCs, among them Bone Morphogenetic Proteins (BMPs) and Notch, both of which promote MuSC proliferation and suppress differentiation. To better understand the mechanisms of function and the target genes regulated by BMP signaling in myogenesis, we investigated the transcriptional responses of adult mouse MuSCs to BMP6/4 using RNA-sequencing. BMP6/4-stimulation of freshly isolated MuSCs for one hour rapidly increased the expression of classical BMP target genes like Id1 and strongly induced expression of genes of the Notch pathway (Hes1, Hey1, Lfng, Snai1). In parallel, using Cleavage Under Targets and Tagmentation (CUT&Tag), we generated whole-genome binding profiles for the BMP pathway effectors pSMAD1/5/9 and SMAD4 and detected binding in promoters and potential regulatory elements of BMP targets and Notch pathway genes (Hes1, Hey1, Lfng, Snai1) indicating that BMP signaling directly influences Notch and that crosstalk between the two pathways regulates myogenesis.

overall_design:
RNA-seq of BMP6- or BMP4-stimulated and control adult mouse muscle stem cells, two biological replicates

UPDATE: [Mar-06-2026] The Sample titles were updated. The old titles are in the Sample description field.

first: Birthe

last: Lange

first: Ioanna

last: Polydorou

first: Helge

last: Amthor


title: Single-cell analysis of chromatin accessibility in the adult mouse brain

status: Public on Nov 02 2023

city: La Jolla

first: Songpeng

last: Zu

state: CA

address: 9500 Gilman Dr

department: Department of Cellular and Molecular Medicine

institute: University of California San Diego

summary:
Here we report a comprehensive atlas of candidate cis-regulatory DNA elements (cCREs) in the adult mouse brain, generated through examination of the chromatin accessibility in 2.3 million individual brain cells from 117 anatomical dissections. The atlas includes approximately 1 million cCREs and their chromatin accessibility across 1482 distinct brain cell populations, adding over 446,000 new cCREs to the most recent such annotation in the mouse genome. Raw fastq files are demultiplexed. Out of 234 samples, fastq files for 6 samples are available in NCBI under the accession number GSE126724 (CEMBA180308_3B, CEMBA180312_3B, CEMBA180226_1A, CEMBA180227_1A, CEMBA180305_2B, CEMBA180306_2B). Processed data are SnapATAC2 (<= 2.4.0) h5ad files per sample, with raw fragments and 500-bp bmat.

Important note:
- Due to the break changes in SnapATAC2 >= 2.5.0, the data can not be handled rightly in SnapATAC2 >= 2.5.0.
- In GSE246791_wmb_enhancer.tar.gz, the subclass-specific bedpe files can be downloaded here: https://catlas.org/catlasv1/wholemousebrain/data/pdc/.

overall_design: We generated single-nucleus assys for transposase-accessible chromatin using sequencing (snATAC-seq) libraries from 117 anatomic dissections of mouse brain and two replicates for each dissection.

first: Yang

last: Li

first: Seoyeon

last: Lee

first: Sebastian

last: Preissl

first: Bing

last: Ren


title: Extensive Crosstalk between BMP and Notch Signaling Pathways in Activated Adult Muscle Stem Cells [array]

overall_design:
Microarray of BMP6-stimulated and control adult mouse muscle stem cells, three biological replicates

UPDATE: [Mar-06-2026] The Sample titles were updated. The old titles are in the Sample description field.


title: Serum miRNA Seq of Children with Asthma in Costa Rica

status: Public on Oct 09 2023

first: Joanne

last: Sordillo

state: MA

address: 181 Longwood Avenue

department: Channing Division of Network Medicine

institute: Mass General Brigham

summary: Small RNA was sequenced from banked peripheral blood serum from 1,134 asthmatic children aged 6 to 14 years who participated in the Genetics of Asthma in Costa Rica Study (GACRS). We filtered the participants into high and low bronchodilator response (BDR) quartiles and used DeSeq2 to identify miRNAs with differential expression (DE) in high (N= 277) vs low (N= 278) BDR group. The putative target genes of DE miRNAs were identified, and pathway enrichment analysis was performed. Results: We identified 10 down-regulated miRNAs having odds ratios (OR) between 0.37 and 0.76 for a doubling of miRNA counts and one up-regulated miRNA (OR=2.26) between high and low BDR group. Further, functional annotation of 11 DE miRNAs were performed as well as of two replicated miRs. Target genes of these miRs were enriched in regulation of cholesterol biosynthesis by SREBPs, ESR-mediated signaling, G1/S transition, RHO GTPase cycle, and signaling by TGFB family pathways.

overall_design: Serum from children with asthma was sequenced. After QC, 1134 subjects showed a total of 317 miRNAs.

first: Rinku

last: Sharma

first: Michael

last: McGeachie


title: Changes in gene expression time 0 vs. 1hr post-cataract sugery wounding in the lens

status: Public on Nov 04 2023

city: Philadelphia

first: Janice

middle: Lynn

last: Walker

state: PA

address: 1020 Locust Street; 571 JAH

department: Pathology and Genomic Medicine

institute: Thomas Jefferson University

summary: Early changes in the transcriptome associated with lens wounding in an ex vivo post-cataract surgery chicken model. Here we report the changes in the transcriptome that occur 1hr vs. time 0 post-cataract surgery wounding. Our data provide a molecular framework for understanding the early gene changes associated with the injury response of the lens.

overall_design:
To determine changes in the transcriptome that occur time 0 compared to 1 hour (1h) post lens wounding.
We here report the changes in the transcriptome that occur 1hr vs. time 0 post-cataract surgery wounding.
Comparative gene expression profiling analysis of RNAseq data for ex vivo chick post-cataract surgery explants performed at time 0 and 1h post-injury

first: Morgan

last: Basta


title: 5-methyl cytosine profile of the wild type and Mpmet mutant in Marchantia polymorpha

status: Public on Sep 21 2023

city: Ikoma

first: Tetsuya

last: Hisanaga

state: Nara

address: Takayama 8916-5

institute: Nara Institute of Science and Technology

type: Methylation profiling by high throughput sequencing

summary: To understand a role of MpMET in maintenance of cytpsine methylation and transposon silencing, we obtained a genome wide profile of 5-methylated cytosine from the Mpmet mutant of a model liverwort, Marchantia polymorpha.

overall_design: Tagmentation-based whole-genome bisulfite sequencing (T-WGBS) for a whole genome profile of cytosine methylation

first: Arie

last: Fridrich

first: Frederic

last: Berger


title: Maternal obesity disrupts epigenetic reprogramming via peroxisomal-dependent phospholipid-methyl uncoupling during zygotic genome activation

status: Public on Sep 25 2023

city: Zhengzhou

first: Lin-Li

last: Yang

state: Henan

address: No. 1, Jianshe East Road, Erqi District

department: department of obstetrics and gynecology

institute: The First Affiliated Hospital of Zhengzhou University

summary: Maternal obesity is known to cause systemic lipid dysregulation, yet its effect on lipid reprogramming during the maternal-to-zygotic transition (MZT) remains unknown. Here we show that obesity disrupts very-long-chain fatty acid (VLCFAs) storage in oocytes and downregulates PEX13, impairing peroxisomal protein import in 2-cell embryos. Normally, peroxisomal β-oxidation converts oocyte-stored VLCFAs into medium- and long-chain fatty acids, which fuel triglyceride synthesis and drive phosphatidylethanolamine (PE) methylation to phosphatidylcholine (PC). This metabolic flux consumes methyl donors to facilitate H3K4me3 erasure and zygotic genome activation (ZGA). In obese mice, VLCFA deficiency and PEX13 dysfunction lead to metabolic-epigenetic uncoupling, depleting lipid droplets and sustaining H3K4me3, thereby suppressing ZGA and blastocyst development. Importantly, supplying long-chain fatty acids or overexpressing PEMT restores the phospholipid-methyl cycle, rescuing epigenetic reprogramming and development. Our findings establish peroxisomal β-oxidation as a metabolic-epigenetic nexus essential for MZT and reveal a phospholipid-methyl coupling mechanism underlying obesity-associated embry development, offering novel therapeutic entry points to improve fertility in metabolic disorders.

overall_design: control embryo compared with siAcox1-2-cell embryo of H3K4me3 modification by CUT&Tag

first: Linli

first: Guohui

last: Zhangxiao

first: Xie

last: Feng

first: Shiming

last: Luo

first: Qingyuan

last: Sun

first: Xianghong

last: Ou


title: Effect of MpMET loss of function on gene and TE expression in Marchantia polymorpha

summary: To evaluate role of MpMET on transcriptional regulation in bryophytes,   we performed comparative transcriptome  analyses using data obtained from Mpmet-3 described in Ikeda et al., 2018 and the corresponding wild type accession.

overall_design: Comparative  expression analysis of RNA-seq data for the wild type and Mpmet-3 mutant


title: Transcriptional profiling of male and female MCT-induced rats with compensated and decompensated right ventricle

first: Fatemeh

last: Khassafi

summary: We performed molecular phenotyping of RV remodeling, using transcriptome analysis of RV tissue obtained from MCT-induced rats (of both male and female animals). The clustering approach along with precise hemodynamics assessments identified “early" and "late" subgroups of decompensated state in rat RV. Further molecular characterization of these subgroups identified distinct molecular genes and pathways within different stages of RV remodeling. This study provided a resource to comprehensively compare human RV remodeling with the current animal model of PH (MCT), and led to validation of state-specific biomarkers and potential therapeutic targets for RV dysfunction.

overall_design: RNA sequencing was performed for two batches of RV tissues obtained from MCT-induced rats (n=53) which were characterized as compensated RV, decompensated RV, as well as normal RV from control rats. Batch 1 include only male samples as follows: control (n=10), compensated RV (n=7), early decompensated RV (n=3), late decompensated RV (n=6). Second batch includes animals from both sexes as follows: control female RV (n=4), control male RV (n=4), compensated female RV (n=6), compensated male RV (n=5), decompensated female RV (n=3), decompensated male RV (n=5).

first: Prakash

last: Chelladurai

first: Sébastien

last: Bonnet

first: Soni

last: Pullamsetti


title: Combinatorial interpretation of BMP and WNT allows BMP to act as a morphogen in time but not in concentration

status: Public on Oct 10 2023

city: Houston

first: Aryeh

last: Warmflash

state: TX

address: 6100 Main St

institute: Rice University

summary: We performed bulk RNA sequencing of cells exposed to either 300ng/ml of the ligand WNT3A for 6 or 18 hours, or 8μM of the GSK3b inhibitor CHIR99021 for 6 hours, which is commonly used as a substitute for WNT in differentiation. We observed transcriptional activation of the canonical WNT genes WNT3 and WNT10B confirming that Wnt signaling induces canonical WNTs.

overall_design: hPSCs were seeded at the density 200k per well in a 12-well plate 24 hours before treatment. hPSCs were grown under 4 experimental conditions: untreated pluripotent cells grown in mTeSR1, hPSCs treated with WNT3a (300ng/ml) for 6 hours, hPSCs treated with WNT3a (300ng/ml) for 18 hours or hPSCs treated with CHIR (8uM) for 6 hours. Total RNA was collected with the Invitrogen RNAqueous-Micro Total RNA Isolation Kit. Processed RNA was stored at −80 ̊C, and RNA integrity was checked by Nanodrop, agarose gel electrophoresis, and qPCR and the Agilent 2100 system. Sequencing was performed by Novogene Co. using the Illumina paired-end 150 platform (Novaseq 6000). Another biological repeat was performed using the same protocol, but also adding a new experimental condition: hPSCs treated with CHIR (8uM) for 18 hours, with two replicates.

first: Elena

last: Camacho-Aguilar

first: Sumin

last: Yoon

first: Miguel

last: Ortiz-Salazar

first: Siqi

last: Du

first: M

middle: C

last: Guerra


title: Transcriptional profiling unveils molecular subgroups of adaptive and maladaptive right ventricular remodeling in pulmonary hypertension

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

sample_organism:
Homo sapiens
Rattus norvegicus

platform_organism:
Homo sapiens
Rattus norvegicus


title: Effect of PRC2 loss of function on gene and TE expression in Cyanidioschyzon merolae

first: Tetsuya

last: Hisanaga

summary: To evaluate role of PRC2 on transcriptional regulation in Cyanidioschyzon merolae, we generated loss of function mutants of a Ez homolog in Cyanidioschyzon merolae by homologous recombination based mutagenesis. Then we performed comparative transcriptome analyses using data obtained from Cme(z) and WT.

overall_design: Comparative expression analysis of RNA-seq data for the Cme(z) mutant and wild type.

first: Frederic

last: Berger

first: Teresa

last: Kowar

first: Daniel

last: Schubert


title: Effect of PRC2 loss of function on gene and TE expression in Marchantia polymorpha

summary: To evaluate role of PRC2 on transcriptional regulation in bryophytes, we generated loss of function mutants of a Ez homolog in Marchantia polymorpha by CRISPR/Cas9 based mutagenesis. To avoid lethality of PRC2 knockout, we first mutate MpKNOX2 gene then additionally knocked MpEz1 out. Then we performed comparative transcriptome analyses using data obtained from Mpknox2 ez1 and Mpknox2.

overall_design: Comparative expression analysis of RNA-seq data for the Mpknox2 mutant and two independent Mpknox2 Mpez1 alleles.


title: Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas [pooled CRISPRi]

status: Public on Sep 15 2023

first: Lukas

last: Chavez

address: 10901 North Torrey Pines Road

department: Cancer Genome and Epigenetics Program, NCI-Designated Cancer Center

institute: Sanford Burnham Prebys Medical Discovery Institute

summary: Circular extrachromosomal DNA (ecDNA) in patient tumor genomes is an important driver of oncogenic gene expression, evolution of drug resistance, and poor patient outcomes. Applying computational methods for detection and reconstruction of ecDNA across a retrospective cohort of 481 medulloblastoma (MB) tumors from 465 patients, we identify circular ecDNA in 82 patients (18%). Patients with ecDNA+ MB were more than twice as likely to relapse and three times as likely to die within 5 years of diagnosis. Individual tumors harbor multiple ecDNA lineages, each containing distinct amplified oncogenes. Multimodal sequencing, imaging, and CRISPR inhibition experiments in MB models reveal intratumoral heterogeneity of ecDNA copy number per cell and frequent putative "enhancer rewiring" events on ecDNA. This study reveals the frequency and diversity of ecDNA in a subset of highly aggressive MB tumors, and suggests copy number heterogeneity and enhancer rewiring as clinically relevant features of ecDNA in MB.

overall_design: Pooled CRISPRi proliferation screen of 32,530 sgRNAs targeting 645 accessible loci on the D458 ecDNA. Cells were lentivirally transformed with CRISPR-dCas9-KRAB and relative sgRNA abundances were counted before and after 21 days.

first: Owen

last: Chapman

first: Jill

last: Mesirov


title: Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas [ATAC-seq]

overall_design: Bulk ATAC-seq of frozen primary medulloblastomas (MB***). ATAC-seq of frozen patient-derived xenograft (PDX) mouse model (RCMB56). ATAC-seq of cell line D458.

first: Ernest

last: Fraenkel


title: Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas

status: Public on Sep 14 2023

overall_design: Refer to individual Series


title: FOS deficiency activates NRF2 signaling and CAF-mediated metabolic symbiosis to induce ferroptosis resistance in lung cancer initiation and brain metastasis

status: Public on Sep 20 2023

first: Shaohua

last: Wang

address: No 12 Middle Wulumuqi Road

institute: Department of Thoracic Surgery

summary: Lung cancer brain metastasis (LCBM) is a leading cause of mortality in lung cancer patients, with a median survival of merely 4-6 months post-metastasis. Ferroptosis, an iron-dependent form of programmed cell death, has emerged as a key regulator of cancer metastasis, yet its role and underlying mechanisms in LCBM remain elusive. This study investigates the involvement of ferroptosis resistance and the transcription factor FOS in LCBM progression. Through single-cell RNA sequencing (scRNA-seq) and clinical sample validation, we identified prominent ferroptosis resistance in LCBM tissues, characterized by elevated expression of resistance markers (e.g., GPX4, SLC7A11) and reduced pro-ferroptotic factors (e.g., ACSL4, TFRC). Functional assays demonstrated that ferroptosis activation inhibits epithelial-mesenchymal transition (EMT) and LCBM both in vitro and in vivo. Notably, FOS expression was progressively downregulated from normal lung tissues to primary lung cancer and LCBM tissues, and FOS overexpression significantly suppressed ferroptosis resistance and brain metastasis. Mechanistically, FOS transcriptionally inhibits the NRF2-SLC3A2-GPX4 axis while promoting the SLC39A8-ACSF2 axis, thereby regulating iron and lipid metabolism to induce ferroptosis. Additionally, FOS overexpression disrupts aberrant crosstalk between lung cancer epithelial cells and cancer-associated fibroblasts (CAFs), blocking CAF-mediated extracellular matrix (ECM) remodeling and cancer cell PD-L1-driven immunosuppression. Notably, FOS overexpression also enhances cisplatin sensitivity in chemo-resistant lung cancer cells, reinforcing its therapeutic potential. Our findings reveal FOS as a critical regulator of ferroptosis and CAF function in LCBM, highlighting targeting FOS and ferroptosis as a novel therapeutic strategy to improve outcomes for lung cancer patients with brain metastasis.

overall_design: Comparative transcriptome analysis of PC-9 lung cancer cells with FOS overexpression (OE) versus control PC-9 cells (Con). The experiment includes 3 biological replicates per group to investigate the regulatory mechanisms of FOS in lung cancer.


title: Transposons repressed by H3K27me3 were co-opted as cis-regulatory elements of H3K27me3 controlled protein-coding genes during evolution of plants

sample_organism:
Marchantia polymorpha
Cyanidioschyzon merolae strain 10D


title: Ablation of dual specificity phosphatase 6 protects against non-alcoholic fatty liver disease via CYP4A and MAPK

status: Public on Sep 04 2023

city: Sendai

first: Can

last: Jiang

state: Miyagi

address: 2-1 Seiryomachi, Aobaku

department: Investigative Pathology

institute: Tohoku University

summary: Dual specificity phosphatase 6 (DUSP6) is a specific phosphatase for mitogen-activated protein kinase (MAPK). In this study, we used a high-fat diet (HFD)-induced murine non-alcoholic fatty liver disease (NAFLD) model to investigate the role of DUSP6 in this disease. Wild-type (WT) and Dusp6-haploinsufficient (HI) mice developed severe obesity and liver pathology consistent with NAFLD when exposed to HFD. In contrast, Dusp6-knockout (KO) mice completely eliminated these phenotypes. Furthermore, primary hepatocytes isolated from WT mice exposed to palmitic and oleic acids exhibited abundant intracellular lipid accumulation, while hepatocytes from Dusp6-KO mice showed minimal lipid accumulation. Transcriptome analysis revealed significant downregulation of genes encoding cytochrome P450 4A (CYP4A), known to promote ω-hydroxylation of fatty acids and hepatic steatosis, in Dusp6-KO hepatocytes compared with WT hepatocytes. Diminished CYP4A expression was observed in the liver of Dusp6-KO mice compared to WT and Dusp6-HI mice. Knockdown of DUSP6 in HepG2, a human liver-lineage cell line, also promoted a reduction of lipid accumulation, downregulation of CYP4A, and upregulation of phosphorylated/activated MAPK. Furthermore, inhibition of MAPK activity promoted lipid accumulation in DUSP6-knockdown HepG2 cells without affecting CYP4A expression, indicating that CYP4A expression is independent of MAPK activation. These findings highlight the significant role of DUSP6 in HFD-induced steatohepatitis through two distinct pathways involving CYP4A and MAPK.

overall_design: Transcriptome sequence analysis used RNA extracted from primary mouse hepatocytes that were treated or not with a mixture of palmitic and oleic acids.

first: Yuriko

last: Saiki

first: Shuto

last: Hirota

first: Kosei

last: Iwata

first: Xinyue

first: Yutaka

last: Ito

first: Keigo

last: Murakami

first: Takehiro

last: Imura

first: Jun

last: Inoue

first: Atsushi

last: Masamune

first: Akiyoshi

last: Hirayama

first: Masafumi

last: Goto

first: Toru

last: Furukawa


title: High-throughput sequencing data of circRNAs in the gastrocnemius muscle of mice with or without right sciatic nerve denervation

status: Public on Sep 08 2023

first: Jin

last: Li

address: 99 Shangda Road

institute: Shanghai University

summary: This study was to identify circRNAs responsible for muscle atrophy. Skeletal muscle wasting is a common clinical feature of many chronic diseases and also occurs in response to acute events. Circular RNAs are covalently closed RNA transcripts that are involved in various physiological and pathological processes. However, the underlying mechanisms of circRNAs implicated in muscle atrophy remains unknown. Global circRNA expression profiling indicated that many circRNAs are involved in the pathophysiological processes of muscle atrophy.

overall_design: The samples used for circular RNA sequencing were gastrocnemius muscle samples from denervated mice with muscle atrophy. The sequencing and analysis were conducted by OE biotech Co., Ltd. (Shanghai, China). For circular RNA sequencing, the total RNA were treated with ribo-zero kit and RNase R to remove ribosomal RNA and linear RNA, respectively. Then constructed cDNA library and qualified by the Agilent 2100 Bioanalyzer, the sequencing was performed by the Illumina sequencer.

first: Junjie

last: Xiao


title: Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas [Hi-C]

first: Lukas

last: Chavez

overall_design: Bulk Hi-C of frozen primary medulloblastomas (MB***). Hi-C of fresh patient-derived xenograft (PDX) mouse model (RCMB56). Hi-C of cell line D458.

first: Owen

last: Chapman

first: Jill

last: Mesirov


title: Gene expression signatures in Arabidopsis thaliana roots under sufficient nitrogen or mild nitrogen deficiency

status: Public on Sep 12 2023

city: Seeland

first: Anja

last: Hartmann

state: Saxony-Anhalt

address: Corrensstraße 3

department: PZB

institute: IPK Gatersleben

summary: To optimize access to nitrogen under limiting conditions, root systems must continuously sense and respond to local or temporal fluctuations in nitrogen availability. In Arabidopsis thaliana and several other species, external N levels that induce only mild deficiency stimulate the emergence of lateral roots and especially the elongation of primary and lateral roots. However, the identity of the genes involved in this coordination remains still largely elusive. In order to identify novel genes and mechanisms underlying nitrogen-dependent root morphological changes, we investigated time-dependent changes in the root transcriptome of Arabidopsis thaliana plants grown under sufficient nitrogen or under conditions that induced mild nitrogen deficiency.

overall_design: Gene expression in whole roots of Arabidopsis thaliana was measured after transferring seven-day-old seedlings for 0, 1, 2 and 4 days to 11.4 mM nitrogen (N-sufficient; control) or 0.55 mM nitrogen (mild N deficiency). Three biological replicates were used.

first: Nicolaus

last: von Wirén

first: Ricardo

last: Giehl


title: Transcriptional profiling of human adaptive and maladaptive right ventricular remodeling

first: Fatemeh

last: Khassafi

summary: In this study, we performed molecular phenotyping of RV remodeling, by transcriptome analysis of RV tissue obtained from 40 patients. The unsupervised clustering analysis identified “early" and "late" subgroups within compensated and decompensated states, characterized by the expression of distinct signaling pathways, and different circulating levels of several ECM proteins in decompensated RV subgroups. Our study provides a resource for the subphenotyping of RV states, the identification of state-specific biomarkers, and potential therapeutic targets for RV dysfunction.

overall_design: RNA sequencing was performed for RV tissues obtained from human patients clinically categorized as compensated RV (n=14), decompensated RV (n=13) and donor controls (n=13). Followed by additional clustering labels, A to E. Cluster A represent Normal group (n=24), Cluster B represent compensated RV group (n=4), Cluster C represent severe hypertrophic RV group (n=3), Cluster D represent early decompensated group (n=5), and Cluster E represent late decompensated group (n=4).

first: Prakash

last: Chelladurai

first: Olivier

last: Boucherat

first: Sébastien

last: Bonnet

first: Soni

last: Pullamsetti


title: Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastomas [scRNA+ATAC-seq]

overall_design: 10X Multiome ATAC and Gene Expression single-nucleus sequencing of primary SHH MB tumor RCMB56-ht.


title: Analysis of the effect of prenatal alcohol exposure on the Placenta—Cortex transcriptomic signature

status: Public on Sep 01 2023

city: Rouen

first: Anthony

last: Falluel-Morel

address: 22 Boulevard Gambetta

institute: Rouen University

summary: Although alcohol consumption during pregnancy is a major cause of behavioral and learning disabilities, most FASD infants are late- or even misdiagnosed due to clinician’s difficulties achieving early detection of alcohol-induced neurodevelopmental impairments. Neuroplacentology has emerged as a new field of research focusing on the role of the placenta in fetal brain development. Several studies have reported that prenatal alcohol exposure (PAE) dysregulates a functional placenta–cortex axis, which is involved in the control of angiogenesis and leads to neurovascular-related defects.   However, these studies were focused on PlGF, a pro-angiogenic factor. The aim of the present study is to provide the first transcriptomic “placenta–cortex” signature of the effects of PAE on fetal angiogenesis. Whole mouse genome microarrays of paired placentas and cortices were performed to establish the transcriptomic inter-organ “placenta–cortex” signature in control and PAE groups at gestational day 20. Genespring   comparison of the control and PAE signatures revealed that 895 and 1501 genes were only detected in one of two placenta–cortex expression profiles, respectively. Gene ontology analysis indicated that 107 of these genes were associated with vascular development, and String protein–protein interaction analysis showed that they were associated with three functional clusters. PANTHER functional classification analysis indicated that “intercellular communication” was a significantly enriched biological process, and 27 genes were encoded for neuroactive ligand/receptors interactors.   Protein validation experiments involving Western blot for one ligand–receptor couple (Agt/AGTR1/2) confirmed the transcriptomic data, and Pearson statistical analysis of paired placentas and fetal cortices revealed a negative correlation between placental Atg and cortical AGTR1, which was significantly impacted by PAE. In humans, a comparison of a 38WG control placenta with a 36WG alcohol-exposed placenta revealed low Agt immunolabeling in the syncytiotrophoblast layer of the alcohol case. In conclusion, this study establishes the first transcriptomic placenta–cortex signature of a developing mouse. The data show that PAE markedly unbalances this inter-organ signature; in particular, several ligands and/or receptors involved in the control of angiogenesis. These data support that PAE modifies the existing communication between the two organs and opens new research avenues regarding the impact of placental dysfunction on the neurovascular development of fetuses. Such a signature would present a clinical value for early diagnosis of brain defects in FASD.

overall_design: From gestational day (GD)15 to GD20, twelve pregnant mice received a daily subcutaneous injection of sodium chloride (NaCl 9‰) or alcohol (3g/kg, Fisher Scientific) diluted in NaCl (50%, v/v). At GD20, placentas and paired fetal cortices were collected, immediately frozen in liquid nitrogen and stored at −80 °C until use.

first: Camille

last: Sautreuil

first: Maryline

last: Lecointre

first: Céline

last: Derambure

first: Carole

last: Brasse-Lagnel

first: Philippe

last: Leroux

first: Annie

last: Laquerrière

first: Gaël

last: Nicolas

first: Sophie

last: Gil

first: Daniel

last: Savage

first: Stéphane

last: Marret

first: Florent

last: Marguet

first: Bruno

last: Gonzalez


title: RNA sequencing identifies human placentalIL3RAas a potential predictor of adverse cardiovascular outcomes in patients with severe preeclampsia

status: Public on Nov 09 2023

first: Mariko

last: Horii

address: 2880 Torrey Pines Scenic Dr

department: Pathology

institute: UCSD

summary: Background: Mortality from preeclampsia (PE) and PE-associated morbidities are 3-to 5-fold higher in persons of African ancestry than in those of Asian and European ancestries. The placenta is central to the etiology of PE. However, how and to what extent the placenta contributes to worse PE outcomes in persons of African ancestry is yet to be fully elucidated.  Objective: We aimed to identify molecular pathways that are unique or enriched in placentas of parturient persons of African ancestry with PE with severe features (sPE) compared to those of Asian and European ancestry with sPE. Study design: Bulk RNA sequencing was performed on 50 placentas from parturient persons with sPE of African (n=9), Asian (n=18) and European (n=23) ancestries and 73 normotensive controls of African (n=9), Asian (n=15) and European (n=49) ancestries. Results: Metabolism, hormone regulation and hypoxia/angiogenesis genes, previously described to be upregulated in PE, including: LEP, PAPPA2, INHA, FSTL3, FLT1, PHYHIP and ENG, were upregulated in sPE across ancestries, with high expression of FSTL3 being additionally associated with intrauterine growth restriction (p<.0001). Notably, LEP, FLT1 and PHYHIP were more highly upregulated in sPE placentas from parturient persons of African versus Asian ancestry. Genes associated with allograft rejection and adaptive immune response were selectively upregulated in placentas from African ancestry parturitions and not in those of Asian and European ancestries. Among the allograft rejection/adaptive immune response genes, IL3RA was of particular interest because the patient with the highest placental IL3RA level, a woman of African ancestry with IL3RA levels 4.5-fold above the average for African ancestry parturitions with sPE, developed postpartum cardiomyopathy, and was the only patient out of 123, that developed this condition. Interestingly, the sPE patients of Asian and European ancestries with the highest IL3RA levels for their ancestries developed unexplained tachycardia peripartum, necessitating echocardiography in the European ancestry patient. The association between elevated placental IL3RA levels and unexplained tachycardia or peripartum cardiomyopathy was found to be significant in the 50 sPE patients (p=.0005). Conclusions: African ancestry parturitions are associated with higher placental upregulation of metabolism (LEP) and hypoxia/angiogenesis (FLT1) genes, and selective upregulation of allograft rejection/adaptive immune response genes, including IL3RA. High placental expression of IL3RA may predict worse maternal cardiovascular outcomes, including peripartum cardiomyopathy. Studies evaluating placental IL3RA levels in peripartum cardiomyopathy cohorts are therefore warranted, as are broader studies evaluating placental factors in maternal cardiovascular outcomes postpartum.

overall_design:
Total RNA-seq of placental RNA from non-hypertensive control and severe preeclampsia from different ancestry

UPDATE: [Jan-10-2024] The Sample ancestry and sex characteristics were updated.

first: Omonigho

last: Aisagbonhi


title: Maternal obesity disrupts epigenetic reprogramming via peroxisomal-dependent phospholipid-methyl uncoupling during zygotic genome activation

status: Public on Sep 07 2023

first: Lin-Li

last: Yang

overall_design: GV oocyte, MII oocyte, Zygote, 2-cell embryo from normal diet mice. GV oocyte, MII oocyte, 2-cell embryo from high-fat diet mice. Control embryos and siAcox1 embryos at 2-cell embryos were performed RNA sequencing.

first: Xiao-Guohui

last: Zhang

first: Xie

last: Feng

first: Yu-Wei

first: Shi-Ming

last: Luo

first: Qing-Yuan

last: Sun

first: Xiang-Hong

last: Ou


title: Transcriptomic comparisons and allele specific expression reveals the electric signal duration divergence in radiative mormyrid electric fish evolution

status: Public on Aug 31 2023

city: Potsdam

first: Feng

last: Cheng

address: Meistersingerstr., 5

institute: University of Potsdam

summary: Electric fishes have independently evolved six times. Most of these fish are weakly electric and they use their discharge mainly for orientation and communication. In the African weakly electric fish genus Campylomormyrus, electric organ discharge (EOD) signals are strikingly different in shape and duration among closely related species, they contribute to pre-zygotic isolation and may have triggered an adaptive radiation. We performed mRNA sequencing on electric organs (EOs) and skeletal muscle (SMs; from which the EOs derive) from three species with short (0.4 ms), medium (5 ms), and long (40 ms) EODs and two different cross-species hybrids. Using pairwise comparison of differential gene expression between EOs and SMs, we identified 1,444 up regulated genes in EO shared by all five species/hybrids cohorts, rendering them candidate genes for EO-specific properties in Campylomormyrus. To understand how gene expression contributes to the variation in EOD duration, we made cross species comparisons among species and tissue. We identified three types of EOD-duration-related expression patterns and several candidate genes, including KCNJ2, KLF5 and SLC24a2, their upregulation may contribute to increased EOD duration, along with a down-regulated gene KCNK6. Hybrids between a short (C. compressirostris) and a long (C. rhynchophorus) discharging species exhibit EODs of intermediate duration and showed imbalanced expression of KCNJ2 alleles. The preferential expression of the C. rhynchophorus allele is in line with a higher expression level in that parental species and points towards a cis-regulatory difference at this locus, relative to EOD duration. A further candidate gene, KLF5, is a transcription factor potentially balancing potassium channel gene expression, a crucial process for the formation of an EOD. Unraveling the genetic basis of the species-specific modulation of the EOD in Campylomormyrus is crucial for understanding the adaptive radiation of this emerging model taxon of ecological (perhaps even sympatric) speciation.

sample_organism: Campylomormyrus compressirostris x Campylomormyrus tshokwe

sample_organism: Campylomormyrus compressirostris x Campylomormyrus rhynchophorus

overall_design: C. tshokwe samples were collected from Brazzaville, Congo river in 2012. Other samples were artifically bred and raised at the Univerrsity of Potsdam. Those fish were anesthetized by a lethal dose of clove oil, and dissected on cold 99% ethanol.  Electric organ and skeletal muscle tissue from each specimen were flash frozen in liquid nitrogen, and further preserved in -80°C.

first: Alice

middle: B

last: Dennis

first: Otto

last: Baumann

first: Frank

last: Kirschbaum

first: Salim

last: Abdelilah-Seyfried

first: Ralph

last: Tiedemann


title: shRNA-based miRNA overexpression results in significant off-target effects caused by isomiR production [mRNA-seq]

status: Public on Aug 22 2023

city: Moscow

first: Anton

last: Zhiyanov

address: 20 Myasnitskaya ulitsa

department: Faculty of Biology and Biotechnology

institute: HSE University

summary: miRNA overexpression strategy based on RNA Polymerase (Pol) III mediated expression of short hairpin RNA (shRNA) coding particular miRNA is widely used for miRNA functional studies. For some miRNAs, e.g., encoded in the genome as a part of a polycistronic miRNA cluster, it is most likely the only way for their individual stable overexpression. Here we have revealed that extra \texttt{U} residues (up to five) added Pol III at the 3$'$-end of the transcribed shRNA associated with a shift in the Dicer cleavage position of the shRNA. This results in the undesirable formation of 5$'$-end miRNA isoforms (5$'$-isomiRs), which have a significantly altered seed region compared to the initially encoded canonical hsa-miR-93-5p. The predominant expression of 5$'$-isomiRs without three or four first nucleotides instead of the canonical isoform could be disclosed based on miRNA-Seq analysis. Moreover, mRNA sequencing data showed that the 5$'$-isomiRs of hsa-miR-93-5p presumably regulate their own mRNA targets. Thus, omitting miRNA-Seq analysis may lead to erroneous conclusions regarding revealed mRNA targets and possible molecular mechanisms in which studied miRNA is involved.

overall_design:
PC-3 (prostate cancer) cell line was transduced by lentiviral particles coding one of the three types of shRNA to achieve stable overexpression of hsa-miR-93-5p.
All shRNA constructs contained the sequence of the canonical hsa-miR-93-5p and differed in their loop sequence only (5'-CUACCUGCACGAACAGCACUUUG-3' -- upper stem; 5'-CUCGAG-3', 5'-UUCAAGAGA-3', 5'-UUCUAAAA-3' -- stem loops; 3'-...UUGAUGGACGUGCUUGUCGUGAAAC-5' -- lower stem).
To comprehensively understand the overexpressed isoforms of hsa-miR-93-5p and their impact on the cellular transcriptome profile, we conducted sequencing of both mRNAs (3 repeats for control and all loops) and miRNAs (3 repeats for the control, 3 repeats for the first loop and 2 repeats for other ones).

first: Diana

last: Maltseva

first: Ivan

last: Kirillov

first: Roman

last: Suvorov

first: Daria

last: Gubani

first: Anna

last: Kudriaeva

first: Alexey

last: Belogurov

first: Alexander

last: Tonevitsky


title: Developmental programming of Kupffer cells by maternal obesity causes fatty liver disease in the offspring II

city: Bonn

first: Elvira

last: Mass

address: Carl-Troll-Str, 31

department: LIMES

institute: University of Bonn

summary: Kupffer cells (KCs) are tissue-resident macrophages which colonize the developing liver early during embryogenesis1. Throughout development and adulthood, KCs have distinct core functions that are essential for liver and organismal homeostasis, such as supporting fetal erythropoiesis as well as postnatal erythrocyte recycling and liver metabolism2. KCs acquire their tissue-specific transcriptional signature immediately after colonizing the liver, mature together with the tissue, and adapt to the tissue’s function1,3,4. However, whether perturbation of macrophage core functions during development may contribute to or cause disease at postnatal stages is poorly understood. Here, we utilize a maternal obesity model to disturb KC functions during gestation. We show that offspring born to obese mothers develop fatty liver disease that is accompanied by a local pro-inflammatory response, a phenotype that is augmented if the offspring is kept on control diet after birth. Further, transcriptional analyses reveal that KCs undergo developmental programming through the maternal high-fat diet, which lasts until adulthood. The offspring’s KC developmental programming is irreversible despite the switch to control diet and leads to increased lipid uptake in hepatocytes mediated via paracrine factors stemming from KCs. The transcriptional programming of KCs and the fatty liver disease phenotype are rescued by genetic depletion of hypoxia-inducible factor alpha (Hif1a) in macrophages during gestation. These results demonstrate that macrophages rely on an undisturbed development to fulfil their core functions and support organ homeostasis during adulthood, and establish developmental programming of KCs as a therapeutic strategy for metabolic disorders, such as fatty liver disease.

overall_design: Three-week-old female mice were initially fed with a control diet (CD) for two weeks and were thereafter divided into two groups: one continued on the CD while the other received a high-fat diet (HFD) for eight weeks. The homeostatic model for insulin resistance (HOMA-IR) was used to assess metabolic changes. Mice with higher HOMA-IR on the HFD were selected to create a maternal obesity model and mice fed with CD were used to generated maternal lean offspring. All females were mated with CD males. Offspring born to maternal obese were cross-fostered to generate both lactating groups and offspring born to maternal lean mothers were crossed-fostered by other maternal lean mothers. Male offspring were weaned into CD or HFD postweaning cages. Livers of offspring were harvested at 11-12 weeks of age and subsequently dissociated into single-cell suspension. Kupffer cells were then sorted using flurescence-activated cell sorting on an BD FACSAria lII cell sorter directly into 500μl QIAzol lysis buffer (Qiagen) and proceeded for sequencing using SMART-Seq2 protocol.

first: Nora

last: Balzer

first: Iva

last: Splichalova

first: Hao

last: Huang

first: Lea

last: Seep


title: shRNA-based miRNA overexpression results in significant off-target effects caused by isomiR production [miRNA-seq]

overall_design:
PC-3 (prostate cancer) cell line was transduced by lentiviral particles coding one of the three types of shRNA to achieve stable overexpression of hsa-miR-93-5p.
All shRNA constructs contained the sequence of the canonical hsa-miR-93-5p and differed in their loop sequence only (5'-CUACCUGCACGAACAGCACUUUG-3' -- upper stem; 5'-CUCGAG-3', 5'-UUCAAGAGA-3', 5'-UUCUAAAA-3' -- stem loops; 3'-...UUGAUGGACGUGCUUGUCGUGAAAC-5' -- lower stem).
To comprehensively understand the overexpressed isoforms of hsa-miR-93-5p and their impact on the cellular transcriptome profile, we conducted sequencing of both miRNAs (3 repeats for the control, 3 repeats for the first loop and 2 repeats for other ones) and mRNAs (3 repeats for control and all loops).


title: Longitudinal DNA methylation in serially passaged primary and modified human astrocytes

status: Public on Jul 21 2023

city: San Diego

first: Morgan

middle: E.

last: Levine

address: 5510 Morehouse Dr

institute: Altos Labs

type: Methylation profiling by genome tiling array

summary: This DNA methylation dataset describes epigenomic changes in in vitro serially passaged primary and immortalized astrocytes, in the context of studies examining cellular aging patterns that are conserved in vivo and in vitro. Primary and fetal hTERT-immortalized astrocytes were grown under normoxic conditions and serially passaged. Longitudinal DNA samples were collected throughout passaging and DNA methylation was measured using the Infinium HumanMethylation850 BeadChip.

overall_design: Primary and fetal hTERT-immortalized astrocytes were cultured and exhaustively passaged in triplicate, both derived from sinlge donors. DNA extraction of primary astrocytes (Creative Biolabs, male) ranged from passage 2 to 10 and fetal hTERT-immortalized astrocytes (Applied Biological Materials, unknown gender) from 12 to 27 (total n= 25 and 45 respectively). Bisulphite converted DNA from samples were hybridised to the Illumina Infinium HumanMethylationEPIC BeadChip.

first: Christopher

last: Minteer

first: Kyra

last: Thrush

first: Peter

last: Niimi

first: Joel

last: Rozowsky

first: Jason

last: Liu

first: Mor

last: Frank

first: Thomas

last: McCabe

first: John

middle: T

last: Gonzalez

first: Erin

last: Hofstatter

first: Mariya

last: Rozenblit

first: Lajos

last: Pusztai

first: Kenneth

last: Beckman

first: Mark

last: Gerstein

first: Albert

last: Higgins-Chen


title: shRNA-based miRNA overexpression results in significant off-target effects caused by isomiR production

status: Public on Aug 21 2023

first: Anton

last: Zhiyanov


title: Developmental programming of Kupffer cells by maternal obesity causes fatty liver disease in the offspring

first: Elvira

last: Mass


title: Profiling Neuronal Methylome and Hydroxymethylome of Opioid Use Disorder in the Human Orbitofrontal Cortex

status: Public on Aug 08 2023

city: Orange

first: Janitza

last: Montalvo-Ortiz

state: CT

address: 200 Edison Road

department: Psychiatry

institute: Yale School of Medicine; West Haven VA Medical Center, VA Connecticut Health Care

summary: Opioid use disorder (OUD) is influenced by genetic and environmental factors. While recent research suggests epigenetic disturbances in OUD, this is mostly limited to DNA methylation (5mC). DNA hydroxymethylation (5hmC) has been widely understudied. We conducted a multi-omics profiling of OUD in a male cohort, integrating neuronal-specific 5mC and 5hmC as well as gene expression profiles from human postmortem orbitofrontal cortex (OUD=12; non-OUD=26). Single locus methylomic analysis and co-methylation analysis showed a higher number of OUD-associated genes and gene networks for 5hmC compared to 5mC; these were enriched for GPCR, Wnt, neurogenesis, and opioid signaling. 5hmC marks also showed a higher correlation with gene expression patterns and enriched for GWAS of psychiatric traits. Drug interaction analysis revealed interactions with opioid-related drugs, some used as OUD treatments. Our multi-omics findings suggest an important role of 5hmC and reveal loci epigenetically dysregulated in OFC neurons of individuals with OUD.

overall_design:
Postmortem orbitofrontal cortex tissue were obtained from the National Post-Traumatic Stress Disorder (PTSD) Brain Bank (NPBB), a brain tissue repository at the U.S. Department of Veterans Affairs (VA). 38 samples were selected, in which 12 individuals were diagnosed with opioid use disorder (OUD+) and 26 without opioid use disorder (OUD-).
Traumatic Stress Brain Research Group
----------------------
Authors state:
The original data is a RRoxBS. However, I only have the beta values table generated using the read counts for each site. I don't have the raw data to submit.

first: Gregory

last: Rompala

first: Sheila

last: Nagamatsu

first: José

last: Martínez-Magaña

first: Diana

last: Nuñez-Ríos

first: Jiawei

last: Wang

first: Matthew

last: Girgenti

middle: H

last: Krystal

last: Gelernter

first: Yasmin

last: Hurd


title: Switching mechanism from AR to EGFR signaling via 3-O-sulfated heparan sulfate in castration-resistant prostate cancer

status: Public on Jul 20 2023

city: Hachioji

first: Shoko

last: Nishihara

state: Tokyo

address: 1-236 Tangi-machi

department: Graduate School of Engineering

institute: Soka University

summary: Expression of HS3ST1 is markedly upregulated in castration-resistant prostate cancer, which proliferates hormone-independently. In a novel mechanism, EGFR–ERK1/2 signaling is activated via 3-O-sulfated HS and EGF/HB-EGF binding in castration-resistant prostate cancer.

overall_design: RNA-seq to compare the expression of  genes between C4-2 cells cultured  in FBS- and CSS- containing meium

first: Hayato

last: Ota

first: Hirokazu

last: Sato

first: Shuji

last: Mizumoto

first: Ken

last: Wakai

first: Kei

last: Yoneda

first: Kazuo

last: Yamamoto

first: Hayao

last: Nakanishi

first: Jun-Ichiro

last: Ikeda

first: Shinichi

last: Sakamoto

first: Tomohiko

last: Ichikawa

first: Shuhei

last: Yamada

first: Satoru

last: Takahashi

first: Yuzuru

last: Ikehara

last: Nshihara


title: Single-cell gene expression profiles of head-and-neck squamous cell carcinoma from a cohort of patients

status: Public on Jul 24 2023

city: Boston

first: Sara

middle: Isabel

last: Pai

state: Massachusetts

address: 55 Fruit Street

department: Department of Surgery

institute: Massachusetts General Hospital

summary: This scRNA dataset was aimed to provide comprehensive profiling of head-and-neck tumor tissues, in order to explore and elucidate patterns of molecular and cellular interactions between the tumor cells and their patient-specific microenvironments. No specific enrichment of a particular cell types were performed to allow comprehensive representation of all cell types. To allow between-patient comparisons, relatively large number of samples from patients with a wide range of patients characteristics and tissue source (primary, recurrence and metastasis) were chosen. The dataset was intended for multiple investigations on specific pathways and cell types of tumor microenvironments.

overall_design:
Fresh tumor samples for scRNAseq were collected from HNSCC patients with signed informed consent under IRB approved protocols [Massachusetts General Hospital (MGH) (IRB#2014P000559; IRB#13-416) and Massachusetts Eye and Ear (MEE).  (IRB#11-024H)]. The 52 samples comprise of 24 primary tumors, 16 local recurrences, and 12 distant metastasis from various organs. The original anatomic site includes oral cavity, larynx/hypopharynx, oropharynx, and nasopharynx. 15 of the samples were HPV-positive.
>>>Raw data for human samples not available due to patient privacy concerns<<<

first: Ruben

last: Bill

first: Pratyaksha

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