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

last: Wirapati

first: Marius

last: Messemaker

first: Whijae

last: Roh

middle: I

first: Moshe

last: Sade-Feldman

first: Mikaël

middle: J

last: Pittet


title: Transcriptional Profiles of Aortic Valve from Calcific Aortic Valve Disease and Normal Control.

status: Public on Jun 28 2023

city: Jinan

first: guo

last: chenghu

address: 07 Wenhua xi road, Jinan, Shandong

country: China

institute: Qilu hospital Shandong University

type: Expression profiling by high throughput sequencing

summary: We report transcriptional profiles of aortic valve tissue from calcific aortic valve disease (CAVD) and normal control (non-CAVD). We collected the aortic valve tissues from five patients with CAVD who underwent aortic valve replacement due to severe aortic valve stenosis. Aortic valve samples from patients with non-calcified aortic valve resection due to heart transplantation (recipient heart) or aortic dissection were collected as the control (non-CAVD). The inclusion criteria for CAVD group were as follows: 50-75 years old; undergoing aortic valve replacement due to severe AVS with significantly valvular calcification. The inclusion criteria for non-CAVD group were as follows: non-calcified aortic valve resection due to heart transplantation (recipient heart) or aortic dissection. For each sample, total RNA was extracted, a cDNA library was generated, and an Illumina NovaSeq 6000 was used to sequence each sample. Stringtie software was used to count the fragment within each gene, and TMM algorithm was used for normalization. Differential expression analysis was performed using R package edgeR. Differentially expressed RNAs with |log2(FC)| value >1, q value [false discovery rate (FDR) adjusted P-value] <0.05, and one group’s mean fragments per kilobase of exon per million reads mapped (FPKM) >1, were assigned as differentially-expressed genes (DEGs).

overall_design: RNA-sequencing was carried out on aortic valve tissues from five patients with calcific aortic valve disease (CAVD) and from four patients with non-calcified aortic valve resection due to heart transplantation (recipient heart) or aortic dissection as control (non-CAVD).

first: Chenghu

last: Guo

first: Xiaoling

last: Liu

first: Guipeng

last: An


title: Genome-scale chromatin interaction dynamic measurements for key components of the RNA Pol II general transcription machinery [ChIP-seq]

status: Public on Jul 27 2023

city: Charlottesville

first: David

last: Auble

state: VA

address: 1349 Jefferson Park Avenue

department: Biochemistry and Molecular Genetics

country: USA

institute: University of Virginia Health System

type: Genome binding/occupancy profiling by high throughput sequencing

summary: A great deal of work has revealed in structural detail the components of the machinery responsible for mRNA gene transcription initiation. These include the general transcription factors (GTFs) which assemble at promoters along with RNA Polymerase II (Pol II) to form a preinitiation complex (PIC) aided by the activities of cofactors and site-specific transcription factors (TFs). However, less well understood are the in vivo PIC assembly pathways and their kinetics, an understanding of which is vital for determining on a mechanistic level how rates of in vivo RNA synthesis are established and how cofactors and TFs impact them. We used competition ChIP to obtain genome-scale estimates of the residence times for five GTFs: TBP, TFIIA, TFIIB, TFIIE and TFIIF in budding yeast. While many GTF-chromatin interactions were short-lived (< 1 min), there were numerous interactions with residence times in the several minutes range. Sets of genes with shared function also shared similar patterns of GTF kinetic behavior. TFIIE, a GTF that enters the PIC late in the assembly process, had residence times correlated with RNA synthesis rates. The datasets and results reported here provide kinetic information for most of the Pol II-driven genes in this organism and therefore offer a rich resource for exploring the mechanistic relationships between PIC assembly, gene regulation, and transcription. The relationships between gene function and GTF dynamics suggest that shared sets of TFs tune PIC assembly kinetics to ensure appropriate levels of expression. Scripts and processed fileas are available from: https://github.com/AubleLab/PIC_competition_ChIP_scripts

overall_design: Competition ChIP (CC) is an approach in which cells harbor two isoforms of a transcription factor of interest with distinguishable epitope tags. We engineered diploid yeast cells to constitutively express one isoform with a Myc tag under control of the endogenous promoter and with the second isoform tagged with HA and under inducible GAL promoter control. In the CC experiments, cells were shifted to galactose at time zero to induce expression of the HA-tagged competitor isoform, followed by cell culture sample collection at 10, 20, 25, 30, 40, 60, 90, and 120 min time points. We then measured the relative occupancies of the Myc- and HA-tagged species genome-wide at each time point and used the relative occupancies as input to a model that describes the competition for chromatin binding to each site and yields the site-specific residence time.

first: Kristyna

last: Kupkova

first: Savera

last: Shetty

first: Stefan

last: Bekiranov

middle: T


title: Effect of ionizing radiation exposure on zebrafish embryo development by single-cell RNA profiling

status: Public on Jul 05 2023

city: 경상남도 양산시

first: Eun Jung

last: Kwon

state: 경상남도

address: Pusan National University, Yangsan,, Republic of Korea

country: South Korea

institute: Pusan National University

summary: Ionizing radiation (IR) affects brain development in vertebrates at early developmental stages, but its effects of IR on other developing tissues have not yet been clarified. To investigate the IR effects on the developing organs, single-cell RNA sequencing was conducted using zebrafish embryos at 24hpf.

overall_design: Thirty 24hpf zebrafish embryos were pooled as a control group(wild type) and IR-exposed group for single-cell RNA sequencing.

first: Eunjung

first: Hansong

last: Lee

first: Chang-kyu

last: Oh

first: Yunhak

last: Kim


title: Identifying colorectal cancer-specific vulnerabilities in the Wnt-driven long-noncoding transcriptome [GRO-seq]

status: Public on Jul 01 2023

city: Amsterdam

first: Nicolas

last: Léveillé

address: Meibergdreef 9

country: Netherlands

institute: Amsterdam UMC

summary: Aberrant Wnt pathway activation is the key driver of colorectal cancer (CRC) development and essential to sustain tumour growth and progression. Although the downstream protein-coding target genes of the Wnt cascade have been well-defined, the long non-coding transcriptome (lncRNAs) has not been resolved in similar detail. We here use global run-on sequencing (GROseq) to define a set of non-coding transcripts that are regulated by the β-catenin/TCF transcriptional complex in CRC.

overall_design:
Use of global run-on sequencing (GROseq) to define a set of non-coding transcripts that are regulated by the β-catenin/TCF transcriptional complex in CRC

**Please note that the records are incomplete as the submitter was unable to provide the correctly-formatted raw data files for the GSM6257143-GSM6257170 samples***

first: Louis

last: Vermeulen

first: Laura

last: Schwarzmüller

first: Ronja

last: Adam

first: Leandro

middle: F

last: Moreno


title: Genome-wide alteration of histone3 lysine23 succinylation contribute to 5-fluorouracil resistance in colon cancer cells

status: Public on Jun 20 2023

city: Shanghai

first: Xuelong

last: Wang

address: No. 100 Banxia Road

institute: Chinese Academy of Sciences

summary: Although widely used in chemotherapy for colon cancer, 5-fluorouracil (5-FU) resistance is the main reason greatly limiting the efficacy of current therapies, leading to poor patient prognosis and survival. Histone lysine succinylation plays a vital role in various diseases by influencing gene expression and chromatin structure. However, limited information is currently available about the role of H3K23 succinylation associated with 5-FU resistance in colon cancer cells (CCCs). Here we explored the systematic alterations of H3K23s succinylation using the Cleavage Under Targets and Tagmentation (CUT&Tag), followed by integrated analysis of multi-omics data to identify potential regulators and their targets associated with differentially enriched regions (DERs) in the parental and 5-FU-resistant HCT15 colon cancer cells. More than 60,000 high-quality peaks were obtained from each sample with higher signal enriched at gene promoter regions. A total of 13,622 H3K23su DERs were identified in 5-FU-resistant HCT15 cells compared to control, which was positively (r = 0.68) correlated with their nearest differentially expressed genes (DEGs). The up-regulated DEGs associated with H3K23su GAIN regions are mainly involved in colorectal cancer, MAPK, Ras, and p53 signaling pathways, while the down-regulated DEGs related to H3K23su LOSS regions significantly enriched in the signaling pathways of Wnt and HIF-1. DNA motif analyses of the DER sequences showed that, besides AP-1, the members of FOX, GATA, and TEAD transcription factor (TF) families were potentially enriched in GAIN or LOSS regions with different preferences. Moreover, differentially expressed TFs and their potential targets associated with H3K23su DERs were identified, including FOSL21, FOXA1 and HNF1B, and known and predicted interactions among these critical TFs were further illustrated. These data provided clear insights and resources for an improved understanding of the role of H3K23su related to 5-FU resistance in colon cancer cells based on the multi-omics data, which allowed for the detection of epigenomic profiles, potential regulatory TFs, cis-regulatory elements, and therapeutic targets.

overall_design: Cleavage under targets and tagmentation (CUT&Tag) was used for detection of H3K23 succinylation and H3K27 acetylation in parental and 5-fluorouracil-resistant HCT15 colon cancer cells, and then integrated analysis of multi-omics data, including mRNA-seq and ATAC-seq, was performed to investigate the role of H3K23su in CCCs associate with 5-FU resistance.


title: Methylome dynamic upon proteasome inhibition by the pseudomonas virulence factor Syringolin A

status: Public on Jul 04 2023

city: Zurich

last: Grob

address: Zollikerstrasse 107

department: Institute of Plant Biology

country: Switzerland

institute: University of Zurich

type: Methylation profiling by high throughput sequencing

type: Non-coding RNA profiling by high throughput sequencing

summary: DNA methylation is an important epigenetic mark required for proper gene expression and silencing of transposable elements. DNA methylation patterns can be modified by environmental factors such as pathogen infection, where modification of DNA methylation can be associated with plant resistance. To counter the plant defense pathways, pathogens produce effectors molecule, several of which act as proteasome inhibitors. Here we investigated the effect of proteasome inhibition by the bacterial virulence factor Syringolin A on genome-wide DNA methylation. We show that Syringolin A treatment results in an increase of DNA methylation at centromeric and pericentromeric regions of Arabidopsis chromosomes. We identify several CHH DMRs that are enriched in the proximity of transcriptional start sites. Syringolin A treatment does not result in significant changes in small RNA composition. However, significant changes in genome transcriptional activity can be observed, including a strong upregulation of resistance genes that are located on chromosomal arms. We hypothesize that DNA methylation changes could be linked to the upregulation of some atypical members of the de novo DNA methylation pathway: AGO3, AGO9 and DRM1. Our data suggests that modification of genome-wide DNA methylation resulting from an inhibition of the proteasome by bacterial effectors could be part of a epi-genomic arms race against pathogens.

overall_design: GWBS, mRNA and sRNA sequencing of wildtype Arabidopsis plantlets treated or not with SyringolinA

first: Pauline

middle: E

last: Jullien


title: The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes (ATAC-seq I)

city: München

first: Caroline

last: Friedel

address: Amalienstr. 17

department: Institut für Informatik

country: Germany

institute: Ludwig-Maximilians-Universität München

summary: We report that HSV-1 gives rise to transposase accessible chromatin in gene downstream areas, in regions that show transcription termination defects. We show that the viral protein ICP22 is responsible for this open chromatin.

overall_design: We used different HSV-1 mutants that lack expression of certain IE genes or VHS and examine the opening of chromatin downstream of transcription termination sites of affected genes. Two biological replicates (four replicates for delta-ICP22) of cells infected with different HSV-1 mutants at MOI 10 were prepared.

first: Lara

last: Djakovic

first: Thomas

last: Hennig

first: Katharina

last: Reinisch

first: Andrea

last: Milic

first: Adam

middle: W

last: Whisnant

last: Wolf

first: Elena

last: Weiß

first: Tobias

last: Haas

first: Arnhild

last: Grothey

first: Christopher

middle: S

last: Jürges

first: Michael

last: Kluge

first: Florian

last: Erhard

middle: C

first: Lars

last: Dölken


title: Profiling immunological phenotypes in individuals during the first year after traumatic spinal cord injury (SCI): a longitudinal analysis

status: Public on May 26 2023

city: Manhasset

first: Ona

last: Bloom

state: New York

address: 350 Community Dr

department: Molecular Medicine

institute: Feinstein Institute

summary: Individuals with SCI are severely affected by immune system changes, resulting in a SCI-induced immune deficiency syndrome (SCI-IDS). While recent data support that acute SCI-IDS symptoms differ from those present in the chronic phase, only limited data in humans is available. To characterize dynamic molecular and cellular immune phenotypes over the first year, we assess RNA (bulk-RNA sequencing), protein, and flow cytometry (FACS) profiles of blood samples from 12 individuals with SCI at 0-3 days and at 3, 6, and 12 months post injury (MPI) compared to 23 uninjured individuals (controls). We identified 967 differentially expressed (DE) genes in individuals with SCI (FDR<0.001) compared to controls. Within the first 6 MPI we detected a reduced expression of NK cell genes, consistent with reduced frequencies of CD56bright, CD56dim NK cells present at 12 MPI. Over 6MPI, we observed increased and prolonged expression of genes associated with inflammation (e.g. HMGB1, Toll-like receptor signaling) and expanded frequencies of monocytes acutely. Canonical T-cell related DE genes (e.g. FOXP3, TCF7, CD4) were upregulated during the first 6 MPI and increased frequencies of activated T cells at 3-12 MPI were observed. Neurological injury severity was reflected in distinct whole blood gene expression profiles at any time after SCI, indicating a persistent ‘neurogenic’ imprint. Overall, 2876 DE genes emerge when comparing profiles of motor complete to motor incomplete SCI (ANOVA, FDR<0.05), including genes related to neutrophils, inflammation, and infection. In summary, we identify dynamic SCI-IDS determinants in humans, including molecular and cellular profiles, which may provide potential targets to reduce inflammation, improve immunity, or serve as candidate biomarkers of injury severity.

overall_design: RNAsequencing from whole blood taken from participants with SCI within 3 days of injury, at 3 MPI, 6 MPI and 12 MPI. Data was compared to un-injured participants as controls. Inclusion and exclusion criteria was applied.

first: Debra

last: Morrison

first: Camille

last: Pinpin

first: Annette

last: Lee

first: Cristina

last: Sison

first: Ashley

last: Chory

first: Peter

middle: K

last: Gregersen

first: Gail

last: Forrest

first: Steven

last: Kirshblum

first: Susan

last: Harkema

first: Maxwell

last: Boakye

first: James

last: Harrop

middle: N

last: Bryce

first: Jan

middle: M

last: Schwab

first: Brian

last: Kwon

middle: B

last: Stein

first: Matthew

middle: A

last: Bank


title: Multipotent neural stem cells originating from neuroepithelium exist outside of the mouse central nervous system

status: Public on Jun 02 2023

city: Muenster

first: Marcos

middle: J.

last: Araúzo-Bravo

address: Rogentstrasse

department: Cell and Developmental Biology

institute: Max Planck Institute for Molecular Biomedicine

summary:
It has been widely accepted that mammalian neural stem cells (NSCs) only exist in central nervous system (CNS).
Here, we challenge this concept and show that peripheral NSCs (pNSCs) could be isolated out of CNS from mouse embryonic limbs,  postnatal tail and adult lung tissues. Derived-pNSCs express multiple NSC-specific markers, exhibit cell morphology, self-renewing capacity, genome-wide transcriptional profile, epigenetic features similar to those of brain control NSCs.
Derived-pNSCs can differentiate into astrocytes, electrophysiologically functional neurons, and oligodendrocytes in vitro and in vivo, indicating multipotency.
Lineage-tracing results reveal that pNSCs are progeny cells of neural epithelial cells, but not neural crest cells.
Our finding of pNSCs out of CNS expands the field of developmental neuroscience and presents an alternative potential strategy for neural regenerative therapy.
Generation of pNSCs:
To generate pNSCs, embryonic limbs cells, adult lung cells and postnatal tail cells were cultured in simple defined NSC medium:
DMEM/F-12 [1:1] with 2% B27 w/o Vitamin A, 1% N2 (both Gibco), 1x Glutmax (Gibco), 1x penicillin-streptomycin (Sigma),
supplemented with 10 ng/ml EGF and 10 ng/ml human bFGF (both from Invitrogen).
Medium was changed every 24h. After pNSCs clusters were observed, each single cluster colony was manually picked and cultured in 96 well individually.
Microarray and data analysis:
RNA samples to be analysed by microarrays were prepared using Qiagen RNeasy columns with on-column DNA digestion.
300 ng of total RNA per sample was used as input into a linear amplification protocol (Ambion) that involved synthesis of T7-linked double-stranded cDNA and 12 h of in vitro transcription incorporating biotin-labelled nucleotides.
Purified and labelled cRNA was then hybridized for 18 h onto MouseRef-8 v2 expression BeadChips (Illumina) following the manufacturer’s instructions.
After washing as recommended, chips were stained with streptavidin-Cy3 (GE Healthcare) and scanned using the iScan reader (Illumina) and accompanying software.
Samples were exclusively hybridized as biological replicates. The bead intensities were mapped to gene information using BeadStudio 3.2 (Illumina).
Background correction was performed using the Affymetrix Robust Multi-array Analysis (RMA) background correction model.
Variance stabilization was performed using the log2 scaling and gene expression normalization was calculated with the method implemented in the lumi package of R-Bioconductor.

overall_design:
12 samples were analyzed
elpNSCs-early, mouse early embryonic limb (el) peripheral Neural Stem Cell (pNSC), 2 replicates
alpNSCs-early, mouse early adult lung (al) peripheral Neural Stem Cell (pNSC), 2 replicates
elpNSCs-late, mouse late embryonic limb (el) peripheral Neural Stem Cell (pNSC), 2 replicates
alpNSCs-late, mouse late adult lung (al) peripheral Neural Stem Cell (pNSC), 2 replicates
Control-NSC, mouse control Neural Stem Cell (NSC), 2 replicates
Fibroblasts, mouse fibroblast, 2 replicates

first: Dong

last: Han

first: Hyun-Woo

last: Jeong

first: Kathrin

last: Hemmer

first: Yaroslav

last: Tsytsyura

first: Guangming

last: Wu

first: Kee-Pyo

last: Kim

first: Henrik

last: Renner

first: Daniela

last: Gerovska

first: Jürgen

last: Klingauf

first: Jens

last: Schwamborn

first: Ralf

middle: H

last: Adams

first: Hans

middle: R

last: Schöler


title: The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes

first: Caroline

last: Friedel

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

overall_design: Refer to individual Series


title: Regulation of CD8 T cell differentiation by the RNA-binding protein DDX5

status: Public on May 23 2023

city: San Diego

first: John

last: Chang

state: CA

address: UCSD

institute: UC San Diego

summary: The RNA-binding protein DDX5 is a polyfunctional regulator of gene expression, but its role in CD8+ T cell biology has not been extensively investigated. In this study, we demonstrate that deletion of DDX5 reduced differentiation of terminal effector (TE), effector memory (TEM), and terminal effector memory (t-TEM) cells while increasing the generation of central memory (TCM) cells; forced expression of DDX5 elicited the opposite phenotype. DDX5-deficient CD8+ T cells exhibited increased expression of genes that promote TCM cell differentiation, including Tcf7 and Eomes. Together, these findings reveal a role for DDX5 in regulating the differentiation of effector and memory CD8+ T cell subsets in response to microbial infection.

overall_design: WT CD45.1 and Ddx5fl/flCd4-Cre+ CD8+ CD45.1.2 P14 cells were adoptively co-transferred into congenically distinct recipient mice. The recipient mice were infected with 2×105 PFU LCMV 24 hours after transfer and sacrificed on days 4, 7, and 30 post-infection. Splenic P14 T cells were isolated by FACS. About 10,000 cells per sample were loaded into Single Cell G chips (10x Genomics) and partitioned into Gel Bead In-Emulsions in a Chromium Controller (10x Genomics). Single-cell RNA libraries were prepared according to the 10x Genomics Chromium Next GEM Single Cell 3’ v3.1 (Dual Index) User Guide and sequenced on a HiSeq 4000 (Illumina).

first: Tiani

middle: L

last: Louis

first: William

last: Wong

first: Priscilla

last: Yao

first: Nadia

last: Kurd

first: Tiffani

last: Tysl

first: Cynthia

last: Indralingam

first: Shengyun

last: Ma

first: Wendy

last: Huang


title: The SARS-CoV-2 Spike protein modifies the transcriptional profile of human cardiac pericytes

status: Public on May 09 2023

city: Bristol

first: Elisa

last: Avolio

address: Upper Maudlin Street

department: Bristol Medical School

country: United Kingdom

institute: University of Bristol

summary: Human cardiac pericytes express the receptors for SARS-CoV-2 and contribute to microvascular dysfunction in COVID-19 patients. The SARS-CoV-2 capsid Spike protein seems to play a direct role in COVID-19 microangiopathy, but it is not known yet whether the Spike protein alone, without the infectious virus, can induce transcriptional alterations in pericytes. This study investigated the signalling pathways activated by the Spike protein in cultured human cardiac pericytes. We found that 309 RNA transcripts were significantly modulated in pericytes exposed to the Spike protein, with the upregulation of pathways linked to inflammation and viral infection.

overall_design: We analysed 3 primary cultures of human cardiac pericytes, isolated from 3 patients, called A1, B1 and C1. Pericytes were exposed for 48 hours either to a recombinant Spike protein (S1+S2 domains, 1 microgram/mL, produced as described in Avolio et al. 2021 - doi: 10.1042/CS20210735) or PBS vehicle, in the absence of FBS and growth factors. The total RNA was collected for RNA-Sequencing.

first: Paolo

last: Madeddu

first: Prashant

last: Srivastava

first: Costanza

last: Emanueli


title: Tracking B Cell Responses to the SARS-CoV-2 mRNA-1273 Vaccine

status: Public on Jul 07 2023

city: Bethesda

first: Susan

last: Moir

state: Maryland

address: 9000 Rockville Pike

department: NIAID

institute: NIH

summary: The COVID-19 pandemic left an unprecedented social and economic impact on the world. This rapidly evolving global instigated a worldwide effort to develop an effective vaccine. Despite the generation of a protective antibody response in most individuals after two doses of an anti-spike mRNA vaccine, some studies have shown that a poorer response is elicited in some individuals, particularly those that are immunocompromised or elderly. To gain further insight into the cellular mechanisms driving B cell evolution in response to vaccination against SARS-CoV-2, we performed longitudinal single-cell transcriptomic, epitope sequencing (CITE-seq), and repertoire profiling of three COVID-19 vaccinees. Spike-specific (S-2P+) B cells showed early immune activation at v1D14 (14 days after vaccine dose 1) and accumulation of somatic hyper mutation (SHM) up to v2M6 (months 6). At v2D6, the S-2P+ cells expanded into memory B cell (MBC) cluster 5 with a dynamic kinetics over time. At v2M6, majority of S-2P+ cells were into resting memory (RM) subset within cluster 5. Analysis of B cell receptor (BCR) repertoire showed selection of genes commonly detected in neutralizing monoclonal antibodies from COVID-19 patients. Tracking of S-2P+ B cell response showed clonal association between earlier activated CD38+ memory, as well as tissue-like memory, with RM B cells at v2M6. These clones showed evolving signal with progressive accumulation of SHM over time. The presence of early plasmablast (PB) within these clones corroborates our previous report that associates PB response with sustained immunity. This integrated analysis allowed us to characterize the transcriptional activity underpinning the development of B cells involved in inducing an immune response to the COVID-19 vaccine.

overall_design: B cells of COVID-uninfected individuals who received Moderna mRNA-1273 vaccine were isolated from thawed cryopreserved PBMC. Spike-specific and non-specific B cells, and total plasmablast were sorted. Cells from all individuals were pooled evenly before cell sorting. Multiple cell pools were prepared, such that cells from the same donors but different time points were in different pools. After cell sorting, cell pools were Fc blocked, CITE-seq and hashtag stained with custom TotalSeq-C cocktail antibodies. Single-cell gene expression (GEX), cell surface protein (ADT) and B cell receptor (BCR) libraries were prepared as instructed by 10x Genomics Single Cell Immune Profiling kit v.2 user guide and sequenced on Illumina NovaSeq 6000 platform. Cells from each donor were demultiplexed in silico using donor-specific single nucleotide polymorphism (SNP) information collected during data analysis. Data were analyzed using Seurat package in R.

first: Felipe

last: Assis

first: Kenneth

last: Hoehn

first: Xiaozhen

last: Zhang

first: Omar

last: El Merhebi

first: Lela

last: Kardava

first: Connor

last: Smith

first: Clarisa

last: Buckner

first: Wei

last: Wang

first: Vicky

last: Chen

first: Paul

last: Schaughency

first: Foo

last: Cheung

first: Justin

last: Lack

first: Steven

last: Kleinstein


title: IRSN-23 Prospective Analyses

status: Public on May 19 2023

city: Suita

first: Yoshiaki

last: Sota

state: Osaka

address: Yamadaoka 2-15

department: Breast and Endocrine Surgery

country: Japan

institute: Osaka University

summary: PURPOSE: The IRSN-23 model uses DNA microarray analysis of tumor tissue to personalize patients into highly sensitive chemotherapy (Gp-R) or less sensitive (Gp-NR) based on the expression of immune-related genes. This study assessed the reproducibility of the IRSN-23 in prospective independent validation sets and investigated its clinical significance and impact on breast cancer subtype classification.  METHODS: Tumour tissues were collected from 146 breast cancer patients undergoing preoperative chemotherapy (paclitaxel-FEC) ± trastuzumab in Osaka University Hospital (OUH). Patients were classified into Gp-R or Gp-NR using IRSN-23, and the model was examined for its ability to predict the pathological complete response (pCR). RESULTS: In the OUH prospective dataset, the pCR rate was significantly higher in the Gp-R group (29·3% (11/41)) than in the Gp-NR group (1·4% (1/71)) not using trastuzumab (P = 1·70E-5). CONCLUSION:  This study provides prospective validation of the IRSN-23 in predicting chemotherapy efficacy, demonstrating a high degree of reproducibility.

overall_design: Fresh frozen tumor samples obtained by vacuum-assisted core biopsy from two hundred and sixty three patients were subjected to RNA extraction and hybridization on Affymetrix microarrays.

first: Yasuto

last: Naoi


title: RAB11A and RAB11B redundantly regulate mitotic spindle function in dividing tissue progenitor cells

status: Public on Jun 09 2023

city: Newark

last: Gao

state: NJ

address: 225 University Ave

department: Biological Sciences

institute: Rutgers Newark

summary: To investigate the role of Rab11 isoforms in intestinal epithelial cells and its downstream effects on intestinal homeostasis.

overall_design: Comparative gene expression profiling analysis RNA-seq data for WT, Rab11aKO, Ra11bKO, and Rab11a+Rab11b Double KO whole Jejunumtissue lysates from adult mice.

first: Ivor

last: Joseph

first: Juan

last: Flores


title: Dysregulation of mixed meal-induced gene expression in skeletal muscle in obesity and type 2 diabetes

status: Public on May 05 2023

city: Moscow

first: Pavel

last: Makhnovsky

address: 76A Khoroshevskoye shosse

country: Russia

institute: Institute of Biomedical Problems of the Russian Academy of Sciences

summary: Physical inactivity and western diet are the main factors leading to skeletal muscle (and whole-body) insulin resistance – a defect in insulin-mediated glucose uptake and metabolism – and associated metabolic diseases, such as obesity and type 2 diabetes mellitus (T2D).  The study of the response to a mixed meal (normalized for body mass and/or basal metabolic rate) is of particular interest, as it simulates the physiological response to a typical (daily) single meal that depends on both the secretory function of the beta cells (insulin response) and the sensitivity of skeletal muscle signaling to insulin – variables, which markedly changing during development of insulin resistance and T2D.  We aimed to compare the early transcriptomic response to a mixed meal normalized to body mass in skeletal muscle of healthy subjects and obese patients without (Ob) and with T2D (Ob+T2D).  To investigate the early transcriptomic response we took biopsy samples from the vastus lateralis muscle prior to and 1 h after a meal. In the Ob+T2D group the average level and increase in C-peptide and insulin in the blood were comparable with healthy subjects that, apparently, is explained by dysfunction of the beta-cells induced by chronic T2D. At the same time, the Ob+T2D group demonstrated dysregulation of mixed meal-induced gene expression in skeletal muscle: morу than two times lower number of DEGs and a small overlapping with the gene response in the control group. On the contrary, the postprandial level of C-peptide and insulin in the Ob group was significantly greater than in healthy control that is related to insulin oversecretion associated with insulin resistance.  Despite this, the gene response in skeletal muscle was also significantly dysregulated; moreover, it differed from the response in the Ob+T2D group.  It means that defect in regulation of insulin-induced gene expression (insulin resistance in terms of gene expression) appears at the first stage of the development of metabolic disorders.

overall_design: Seven healthy subjects, 7 obese patients, and 7 obese patients with T2D were involved in the study.  Subjects arrived at the laboratory at 09:00 after 12 h overnight fast. The venous blood was drawn from the v. intermedia cubiti using catheter prior to, and at 30, and 60 min after the mixed meal tolerant test (MMTT; nutritional drink Resource 2.0 [Nestle Health Science, France], 3 ml/kg of body mass, protein:lipid:carbohydrate 9:9:21, 840 kJ/100 ml). The plasma concentration of glucose and glycated hemoglobin was evaluated using an automatic analyzer Architect c8000 (Abbott Diagnostics, USA) and by HPLC (analyzer D10, BioRad, USA); the serum concentration of insulin and C-peptide was evaluated using an automatic analyzer Cobas 6000 (Roche, Switzerland). Biopsy samples were taken under local anesthesia (2 ml 2% lidocaine) using a modified Bergström needle with manual suction from the left vastus lateralis muscle prior to and after the MMTT.

first: Daniil

last: Popov

last: Makhnovskii


title: Hippocampus-specific transcriptome profiling after severe cerebral hypoperfusion in mice

status: Public on Jul 26 2023

first: Zengyu

last: Zhang

state: Shanghai

address: Dong'an Road

department: Neurology

institute: Fudan University

summary:
Little is understood about the underlying cellular and molecular mechanisms related to hippocampus damage and glial activation after severe cerebral hypoperfusion.Efforts to explore the relationship between neuropathological and gene expression changes support a role for identifying novel molecular pathways by transcriptomic mechanisms.
To investigate hippocampus-specific transcriptome profiling after severe cerebral hypoperfusion in mice

overall_design: Hippocampus-specific gene expression profiling analysis was performed using data obtained from RNA-seq of 3 biological replicates in sham and BCAS mice after hypoperfusion

first: Shaungxing

last: Hou


title: Stem cell decoupling underlies impaired lymphoid development during aging [scATAC-seq]

status: Public on Apr 27 2023

city: Bordeaux

first: Stephania

last: Contreras Castillo

address: 2, Docteur Hoffman Martinot

country: France

institute: Université de Bordeaux

summary: Mammalian aging is associated with multiple defects of hematopoiesis, most prominently with the impaired development of T and B lymphocytes. This defect is thought to originate in hematopoietic stem cells (HSCs) of the bone marrow, specifically due to the age-dependent accumulation of HSCs with preferential megakaryocytic and/or myeloid potential ("myeloid bias"). Here we tested this notion used inducible genetic labeling and tracing of HSCs in unmanipulated animals. We found that the endogenous HSC population in old mice shows reduced differentiation into all lineages including lymphoid, myeloid and megakaryocytic. Single-cell RNA sequencing and immunophenotyping (CITE-Seq) showed that HSC progeny in old animals comprised balanced lineage spectrum including lymphoid progenitors. Lineage tracing using the aging-induced HSC marker Aldh1a1 confirmed the low contribution of old HSCs across all lineages. Competitive transplantations of total bone marrow cells with genetically marked HSCs revealed that the contribution of old HSCs was reduced, but compensated by other donor cells in myeloid cells but not in lymphocytes. Thus, the HSC population in old animals becomes globally decoupled from hematopoiesis, which cannot be compensated in lymphoid lineages. We propose that this partially compensated decoupling, rather than myeloid bias, is the primary cause of the selective impairment of lymphopoiesis in the old age.

overall_design: Two old (20 months)Pdzk1ip1-CreER R26Tom/Tommice were induced with 1mg of tamoxifen. After 7 days post-induction Lin- Sca-1+ c-Kit+ CD150+ CD48- HSCs (entire HSC population) were sorted and pooled. Note that tdTomato expression was not used for sorting, but tamoxifen-induced mice were used for consistency with other experiments.

first: Geunhyo

last: Jang

first: Eduardo

last: Esteva

first: Samik

last: Upadhaya

first: Jue

last: Feng

first: Nicholas

last: Adams

first: Elodie

last: Richard

first: Rajeshwar

last: Awatramani

first: Catherine

last: Sawai

first: Boris

last: Reizis


title: Stem cell decoupling underlies impaired lymphoid development during aging [scRNA-seq]

overall_design: CITE-seq datasets: Lin-cKit+Tom+ and Lin-Flt3+Tom+ cells were isolated using Fluorescence-activated Cell Sorting (FACS) at 4 weeks and 8 weeks after tamoxifen induction, respectevely. Three old (20 months) and three young (3 months) mice (Pdzk1ip1-CreER R26Tom/Tom) were used for each timepoint.


title: RNAseq of wild type and maternal Eevs mutant (Meevs) zebrafish embryos

status: Public on Apr 20 2023

city: Salt Lake City

first: James

last: Gagnon

state: UT

address: 1390 Presidents Circle, Crocker Science Center Receiving, Crocker Science Center Receiving

institute: University of Utah

summary: Goal of this study is differential gene expression between wild type and Meevs mutants after UVB exposure

overall_design: Triplicates of wild type and Meevs embryos mock-exposed or 450 J UVB exposed at 24 hpf, collected 5 hours post exposure or 24 hours post exposure

first: Marlen

last: Rice

first: Julane

last: Machado


title: NAT10 promotes the progression of clear cell renal cell carcinoma by regulating ac4C acetylation of NFE2L3 and activating AKT/GSK3β signaling pathway [ChIP-seq]

status: Public on Mar 18 2023

city: Jinan

first: Zenghui

last: Sun

address: 44 Wenhua West Road, Lixia District

institute: Shandong university

summary: In order to determine how NAT10 regulates NFE2L3 to promote the progression of ccRCC, since NFE2L3 is a transcription factor, we performed CHP-seq detection for NFE2L3, as well as RNA-seq detection for 786-O cells with stable NFE2L3 knocking and control 786-O cells. The results of RNA-seq showed that 312 transcripts in the NFE2L3 knockdown group were down-regulated, and 3 114 transcripts in the previous ccRCC tissue were up-regulated. Moreover, after comprehensive analysis of ChIP-seq, there were 12 overlapping transcripts. Analysis of the expression levels of 12 transcripts in control cells and stable NFE2L3 knockout cells  showed that the expression level of LASP1 was the highest in cells, so we hypothesized that NFE2L3 promoted the progression of ccRCC by affecting LASP1.

overall_design: chip-seq was performed directly with 786-O cells

first: Wenjuan

last: Li


title: Gene expression profile at single cell level of human pulmonary arteries (PA) of healthy and Pulmonary hypertension affected lungs

status: Public on Mar 31 2023

city: Graz

first: Francesco

last: Valzano

address: Neue Stiftingtalstraße 6, 8010 Graz

country: Austria

institute: Ludwig Boltzmann Institute for lung vascular research

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: NAT10 promotes the progression of clear cell renal cell carcinoma by regulating ac4C acetylation of NFE2L3 and activating AKT/GSK3β signaling pathway [RNA-seq]

overall_design: Knock down NFE2L3 786-O cells and control 786-O cells


title: Notochord and axial progenitor generation by timely BMP and NODAL inhibition during vertebrate trunk formation (human)

status: Public on Mar 06 2023

city: London

first: Tiago

last: Rito

address: 1 Midland Rd

institute: The Francis Crick Institute

summary: The formation of the vertebrate body is driven by the progressive and coordinated production of trunk tissues from pools of progenitors located in the posterior of the embryo. Aspects of this process are recapitulated by in vitro models based on pluripotent stem cells (PSCs). However, these models lack several tissue components normally found in the vertebrate trunk. Most strikingly, the notochord, a hallmark of chordates and the source of midline signals that pattern surrounding tissues, is absent from current models of human trunk formation. To investigate how trunk tissue is formed, we performed single-cell transcriptomic analysis of chick embryos. This delineated molecularly discrete progenitor populations, which we spatially locate in the embryo and relate to signalling activity. Guided by this map, we determined how a stereotypical spatial organization of tissue types arises in differentiating human PSCs. This involved LATS1/2 mediated repression of YAP activity facilitating WNT signalling, that, together with FGF mediated ERK1/2 activation, induces the transcription factor Bra/TBXT. In addition, timely inhibition of a WNT-induced NODAL and BMP signalling cascade regulates the proportions of different tissue types produced, including notochordal cells. We exploit this to develop an integrated 3D model of human notochord and neural tissue formation. Together the data provide insight into the mechanisms responsible for the formation of the tissues that comprise the vertebrate trunk and pave the way for future studies of patterning in a tissue-like environment.

overall_design: To investigate the emergence of axial progenitor pools and the trunk tissues they generate, we developed an in vitro assay using the human embryonic stem cell line H9 growing on micropatterned laminin substrates. The control dataset employs WNT(CHIR) + FGF together with BMP and NODAL inhibition for 3 days. The two remaining datasets have a 24h and 48h delay in the addition of BMP and NODAL inhibitors whilst keeping the same day3 end-point. Cells of all conditions were dissociated and the transcriptome of single cells analysed using the 10X Genomics platform (Single Cell 3′ v3.1).

first: Ashley

last: Libby

first: Maddy

last: Demuth

last: Briscoe


title: NAT10 promotes the progression of clear cell renal cell carcinoma by regulating ac4C acetylation of NFE2L3 and activating AKT/GSK3β signaling pathway

summary: To determine the role of NAT10 in promoting the progression of ccRCC, we performed RNA sequencing (RNA-Seq) and ac4C-modified RNA immunoprecipitation sequencing (acRIP-seq) on four pairs of ccRCC tissues and their adjacent tissues. A comprehensive analysis of acRIP-seq and RNA-seq showed that the expression and acetylation levels of 199 transcripts were increased .  We selected 11 candidate genes of interest and analyzed their acetylation levels.  Since ac4C modification can improve mRNA stability, the 11 candidate genes were verified, and the results showed that only NFE2L3 mRNA levels decreased in 786-O cells and A498 cells after NAT10 stable knockdown , so we decided to study the mechanism of action of NFE2L3 in ccRCC.

overall_design: ccRCC tissue and Paracancer tissue


title: Long read proteogenomics to connect disease-associated sQTLs to the protein isoform effectors in disease

status: Public on Mar 01 2023

city: Charlottesville

first: Charles

last: Farber

department: Center for Public Health Genomics

institute: University of Virginia

summary: Genome-wide association studies (GWASs) have revealed thousands of associations in many complex traits and diseases. Previous studies suggest that a subset of associations are due to alterations in splicing; however, interpreting the effects of splicing on protein isoforms is hindered by limitations in defining full-length transcript isoforms using short-read RNA-seq data. Long-read RNA-seq represents a powerful approach to define and quantify transcript isoforms. In this study, we developed a novel approach that integrates information from GWAS, splicing QTL (sQTL), and PacBio long-read RNA-seq in a disease relevant model to infer the effects of sQTL on the ultimate protein isoform products they encode. Such information enables identification of genes potentially responsible for GWAS associations. As a proof-of-concept, we generated deep coverage (N=~22 million full-length reads) PacBio long-read RNAseq data on human fetal osteoblasts (hFOBs), a cell-line of relevance to the regulation of bone mineral density (BMD). We identified 68,326 protein-coding isoforms, including 17,375 (25%) which were novel. Next, we used Bayesian colocalization to identify 1,863 sQTLs from the Genotype-Tissue Expression (GTEx) project in 732 protein-coding genes which colocalized with BMD associations (H4PP > 0.75). A total of 836 junctions with colocalizing sQTLs in 459 (of the 732) genes were expressed in hFOB long-read RNA-seq data. With these data, we formulated hypotheses regarding the potential mechanism of action of each sQTL. For example, we identified 7 junctions with colocalizing sQTLs (maximum H4PP = 0.98-0.99) in TPM2 for splice junctions between two nearly mutually exclusive exons, and two different transcript termination sites, making it impossible to interpret without long-read RNA-seq data. siRNA mediated knockdown in hFOBs showed two TPM2 isoforms with opposing effects on mineralization. Our results suggest that splicing is a major mechanism underlying GWAS associations and long-read proteogenomics data is critical to precisely define the protein isoforms that are produced from splicing alterations.

overall_design: Long-read proteogenomics coupled with sQTL colocalization and experimental validation

first: Abdullah

last: Abood

first: Gloria

last: Sheynkman


title: Long non coding RNA (lncRNA) profiling of the colon epithelium of chronicallly SIV infected Rhesus macaques(RMs) administered either Δ9 THC or Vehicle (VEH)

status: Public on Feb 28 2023

city: San Antonio

first: Mahesh

last: Mohan

state: Texas

address: 8715 West Military Road

department: Host Pathogen Interaction Program

institute: Southwest National Primate Research Center

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

summary: Here, we describe  new information on changes in the lncRNA landscape and their potential role in the pathogenesis of HIV/SIV induced intestinal epithelial dysfunction. Our study provides relevant novel insights on the protective role of the natural anti-sense lncRNA MMP25-AS1 in the colonic epithelium (CE) and its modulation by long-term controlled delta-9-tetrahydrocannabinol (THC) administration during chronic HIV/SIV infection. More specifically, we demonstrate a novel epigenetic mechanism in maintaining intestinal homeostasis by MMP25-AS1 upregulated by THC in CE via direct counteraction of matrix metalloproteinase 25 (MMP25) expression.

overall_design: Differentially expressed lncRNAs and mRNAs was profiled in the CE of chronically SIV infected RMs administered either THC (n = 6, duration = 6 months) or VEH (n = 5, duration = 6 months) and uninfected control (n = 6) animals


title: Granulosa cell mevalonate pathway abnormalities contribute to oocyte meiotic defects and aneuploidy [RNA-seq mouse GC]

status: Public on Feb 26 2023

city: Shanghai

first: Qian

last: Bian

address: Pudong New District, Jinzun Rd, No.115

department: Ninth People’s Hospital

institute: Shanghai Jiao Tong University School of Medicine

summary: The mechanisms of oocyte meiotic defects and low competence during ovarian aging remains elusive for decades. Using Hi-C (genome-wide chromatin conformation capture) and Smart RNA-seq of oocytes from 6- weeks or 10- months aged ovaries, the abnormal loose chromatin structures and disturbing expression of meiosis associated genes at metaphase I phase were disclosed. Furthermore, the transcriptomic landscape of granulosa cells (GCs) surrounding oocytes from young and aged ovaries reveled that oocyte meiotic maturation was accompanied with a robust increased expression of genes involved with the mevalonate (MVA) pathway in GCs from young ovaries but these genes expression was not upregulated to counterpart level in GCs from aged ovaries.The inhibitor of MVA pathway of GCs, Statins significantly decreased polar body extrusion rate and increased the rate of irregularly assembled spindles and misaligned chromosomes remarkably in oocytes of culumus-oocyte complex (COCs) from young ovaries . Correspondingly, the activitor of MVA pathway of GCs, Geranylgeraniol ameliorated ovarian reserve and reduced meiotic defects in oocytes of COCs from aged ovaries. Mechanistically, MVA pathway activation in GCs culminated oocyte meiotic maturation by upregulating EGF signaling via LH receptor on GCs surrounding oocytes. Together, MVA pathway is a promising therapeutic target for prompting quality of oocytes from aged ovaries.

overall_design: In this study, the dynamics of chromatin structure of oocytes and the overall transcriptomic landscape of oocytes and GCs throughout oocyte meiosis (growing phase, full-grown phase, metaphase I phase, metaphase II phase) in vivo from young and aged mice were depicted.

first: Lijun

last: Ding

first: Chuanming

last: Liu

first: Wu

last: Zuo


title: Granulosa cell mevalonate pathway abnormalities contribute to oocyte meiotic defects and aneuploidy [RNA-seq Human Granulosa cells]

overall_design: RNA-seq of human granulosa cells


title: RNA-seq analysis of RNA extracted from control alveolar bone samples and alveolar bone under apical periodontitis

status: Public on Feb 11 2023

city: Chengdu

first: Ping

last: Lyu

address: NO.14, 3rd Section of Ren Min Nan Rd. Chengdu, Sichuan

institute: West China Hospital of Stomatology, Sichuan University

summary: To investigate the underlying mechanisms in the the states of apical periodontitis, we extracted RNA from control alveolar bone and alveolar bone under apical periodontitis.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for RNA extracted from control alveolar bone samples and alveolar bone under apical periodontitis.

first: Yi

last: Fan

first: Quan

last: Yuan

first: Chenchen

last: Zhou


title: Single-cell gene expression of control mandibular bone marrow cells and mandibular bone marrow cells under apical periodontitis

summary: Single-cell gene expression of mandibular bone marrow cells and mandibular bone marrow cells under the stimulation of apical periodontitis were determined by scRNAseq.

overall_design: Twenty C57/B6 male mice with apical periodontitis or control mice were used to acquire single-cell suspensions. Mandibles were dissected under a stereo microscope. Soft tissues, molars, incisors and bone behind the condyle were removed. Then, mandibular alveolar bone tissue was digested to acquire single cell suspension. After red blood cells were lysed, cellular suspensions were loaded into Chromium microfluidic chips and barcoded with a 10x Chromium Controller (10x Genomics).


title: no treatment / nitrate starvation / nitrate induction-Study of the primary nitrate response (PNR) in nlp2 mutant and WT

status: Public on Feb 08 2023

city: Gif sur Yvette

first: Véronique

last: BRUNAUD

address: avenue des sciences

institute: INRAE

summary: ngs2018_11_nlp2-no treatment / nitrate starvation / nitrate induction-Is NLP2 involved in the PNR Nitrate starvation and nitrate induction effects on wild type and mutant nlp2

overall_design: 18 samples with 3 biological replicats. normal vs mutant comparison,treated vs untreated comparison

first: Alexandra

last: Launay-Avon

first: Anne

last: Krapp

first: Ludivine

last: Taconnat-Soubigou


title: Granulosa cell mevalonate pathway abnormalities contribute to oocyte meiotic defects and aneuploidy [Hi-C]


title: Individualized mRNA Neoantigen Vaccines provoke substantial T cell immunity in Pancreatic Cancer

status: Public on Feb 01 2023

city: New York

first: Zachary

last: Sethna

state: NY

address: 417 E 68th Street

institute: Memorial Sloan Kettering Cancer Center

summary: Phase 1 trial of individualized mRNA vaccine for Pancreatic Cancer. We used scRNA-seq to characterize the phenotype of vaccine associated T cells.

overall_design: 5 samples, TCR and GEX

first: Luis

last: Rojas

first: Kevin

last: Soares

first: Cristina

last: Olcese

last: Pang

first: Erin

last: Patterson

first: Jayon

last: Lihm

first: Nicholas

last: Ceglia

first: Alexander

last: Chu

first: Rebecca

last: Yu

first: Adrienne

last: Chandra

first: Theresa

last: Waters

first: Jennifer

last: Ruan

first: Masataka

last: Amisaki

first: Pablo

last: Guasp

first: Abderezak

last: Zebboudi

first: Zagaa

last: Odgerel

first: Evelyna

last: Derhovanessian

first: Felicitas

last: Müller

first: Ina

last: Rhee

last: Yadav

first: Anton

last: Dobrin

first: Michel

last: Sadelain

first: Marta

last: Luksza

first: Noah

last: Cohen

first: Laura

last: Tang

first: Olca

last: Basturk

first: Mithat

last: Gönen

first: Seth

last: Katz

first: Richard

last: Do

first: Andrew

last: Epstein

first: Parisa

last: Momtaz

first: Wungki

last: Park

first: Ryan

last: Sugarman

first: Anna

last: Varghese

first: Elizabeth

last: Won

first: Avni

last: Desai

first: Alice

last: Wei

first: Michael

middle: I

last: D'Angelica

first: T

middle: P

last: Kingham

first: Ira

last: Mellman

first: Taha


title: Single-cell RNA sequencing data of primary and super-charged NK cells

status: Public on Apr 26 2023

city: West Allis

first: Ao

last: Mei

state: Wisconsin

address: 9442 West Maple Ct

institute: Medical College of Wisconsin

summary: NK cells are essential for mediating host immune responses. Approaches to augmenting the immunosurveillance function of NK cells have been extensively studied. Based on multiple publications, super-charged NK cells have been shown to be successfully activated with enhanced cytokine production and cytotoxicity capabilities. Here we use the single-cell RNA sequencing technique to understand the transcriptomic differences between IL-2 cultured and super-charged NK cells. Our data will help improve our understanding of applying NK cells for immunotherapy.

overall_design: Single-cell RNA sequencing analyses of IL-2 cultured and super-charged NK cells derived from the PBMC of healthy donors.

first: Kawaljit

last: Kaur

first: Po-chun

last: Chen

first: Meng-Wei

last: Ko

first: Emanuela

last: Senjor

first: Subramaniam

last: Malarkannan

first: Janko

last: Kos

first: Anahid

last: Jewett


title: Effect of Liraglutide on Experimental Autoimmune Encephalitis Mice Lumbar Spinal Cord

status: Public on Dec 31 2022

city: Shijiazhuang

first: Shuang

last: Song

state: Hebei

address: No.215 Heping West Road

institute: The Second Hospital of Hebei Medical University

summary: Researchers have induced an experimental model of multiple sclerosis [experimental autoimmune encephalomyelitis (EAE)] in C57BL/6 mice to test the neuro-therapeutic effect of Liraglutide during the disease peak and investigate its possible mechanisms.

overall_design:
The experimental conditions to be considered in this study are: 1. Tissue: Lumbar Spinal Cord : 6 samples (tissues are sampled when clinical score peak) ; 2. Treatment: (a) EAE : 3 samples (b) Liraglutide treatment+EAE: 3 samples. For EAE induction, emulsion of Complete Freund's Adjuvant, 4 mg/ml Mycobacterium tuberculosis H37Ra and 0.25mg MOG35-55 was subcutaneously paraspinally injected to the mice, and 500 ng of pertussis toxin was given intraperitoneally twice 0 and 48hours after immunisation.

[04-23-2025] The metadata and processed data for this dataset were updated.

first: Li

last: Guo

first: Bin

last: Li


title: Xenopus laevis lack the critical sperm factor PLCz

status: Public on Feb 06 2023

city: Pittsburgh

first: Joel

last: Rosenbaum

state: PA

address: 4249 5th Ave

institute: University of Pittsburgh

summary: To investigate whether X. laevis have a PLCz ortholog or comparable enzyme.

overall_design: RNA sequencing

first: R

last: Bainbridge

first: J

first: A

last: Carlson


title: Essential roles of the ANKRD31-REC114 interaction in meiotic recombination and mouse spermatogenesis

status: Public on Apr 18 2023

first: Soonjoung

last: Kim

email: kims16@mskcc.org, soonjk@yuhs.ac

address: 430 East 67th Street

department: Molecular Biology

institute: Memorial Sloan Kettering Cancer C

summary: DNA double-strand breaks (DSBs) initiate meiotic recombination. ANKRD31 recently emerged as a DSB regulator particularly important in the pseudoautosomal regions (PARs) of sex chromosomes. ANKRD31 interacts with multiple proteins, including DSB-promoting REC114. To test if this interaction is important, we generated mice with Ankrd31 mutations that either reduced (missense) or eliminated (C-terminal truncation) the ANKRD31–REC114 interaction without diminishing contacts with other partners. Eliminating the interaction mimicked an Ankrd31 null, with delayed DSB formation, defective DSB repair, and altered DSB locations including absence of PAR breaks. When the ANKRD31–REC114 interaction was instead attenuated, DSB formation was again delayed globally, but DSB locations and repair were affected little if at all. The missense Ankrd31 allele showed a dosage effect, wherein combining it with the null or C-terminal truncation allele resulted in intermediate phenotypes. Our results show that ANKRD31 function is critically dependent on its interaction with REC114, and that defects in ANKRD31 activity correlate with the severity of interaction disruption.

overall_design: Detection of single-stranded DNA in the genome of mouse testis cells

first: Jiaqi

last: Xu

first: Scott

last: Keeney


title: Small intestine and colon tissue-resident memory CD8+ T cells exhibit transcriptional, epigenetic, and functional heterogeneity in concert with differential dependence on Eomesodermin

status: Public on Dec 28 2022

city: San Diego

first: John

last: Chang

address: UCSD

institute: UC San Diego

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

overall_design: Refer to individual Series


title: Transcriptome of radially growing Arabidopsis wild type and d14 mutant hypocotyls with single cell resolution revealed by nucleus RNA-seq using 10x Chomium and VASA-seq

status: Public on Apr 04 2023

city: Heidelberg

first: Thomas

last: Greb

address: Im Neuenheimer Feld 360

department: Centre for Organismal Studies

institute: Heidelberg University

summary: Wood formation is fundamental for the remarkable growth of plant bodies by continuously providing cells for long-distance transport of water and nutrients and for mechanical support. Vessel elements, the water transporting units within woody tissues, are generated from a cylindrical domain of cambium stem cells (CSCs) generating different vascular cell types in a bidirectional manner during the radial (secondary) growth. However, knowledge on the regulation of CSC activity is limited with unclear cell fate trajectories as the most obscure aspect in this context. Here, we provide a transcriptome atlas of CSCs and their derivatives at single cell resolution in Arabidopsis thaliana hypocotyl.

overall_design: Nuclei of Arabidopsis thaliana (wild type, PXY:H4-GFP;SMXL5:H2B-RFP) hypocotyls were isolated by Fluorescence-activated nucleus sorting (FANS) based on Hoechst staining and analyzed using snRNAseq by the 10x Genomics pipeline (Library: DSNucseq2). Furthermore, VASA-seq analyses in 384-well plate format were applied to nuclei from whole hypocotyls (three replicate plates, Library: UHE-DS-v011, 012, 013) and cambium enriched nuclei (three replicate plates, Library: UHE-DS-v008, v009, v010) according to the GFP and RFP signal of nuclei during FANS (GFP+ and/or RFP+ nuclei). In addition, hypocotyl nuclei of wild type and d14-1 mutants were isolated and analyzed using snRNAseq by the 10x Genomics pipeline (Library: WT, d14).

first: Shi

last: Dongbo

first: Zhao

last: Jiao

first: Song

last: Changzheng

first: Greb

last: Thomas


title: Small intestine and colon tissue-resident memory CD8+ T cells exhibit transcriptional, epigenetic, and functional heterogeneity in concert with differential dependence on Eomesodermin [scATAC-seq]

summary: Tissue-resident memory CD8+T (TRM) cells are a distinct component of the memory T cell armamentarium found in many tissues. Recent studies have shown disparities among TRM cells across tissues, but it is unknown whether there is heterogeneity among TRM cells from differentanatomic compartments of the small intestine and colon. Herewe show that intestinal TRM cells exhibit distinctive patterns of cytokine and granzyme expression, along with substantial transcriptional, epigenetic, and functional heterogeneity. We elucidate unexpected tissue- and context-specific regulatory roles for the T-box transcription factor Eomesodermin (Eomes), previously described to repressskin, liver, and kidney TRM cell formation, in promoting the maintenance of established TRM cells in the small intestine, but not in the colon. Taken together, these data provide previously unappreciated insights into the heterogeneity and differential requirements for the formation vs. maintenance of TRMcells from the small intestine and colon.

overall_design: Performed scATAC-seq to unterstand look at heterogeneity

first: Yun

last: Lin

first: Han

middle: G

last: Duong

first: Abigail

last: Limary

first: Eleanor

first: Paul

last: Hsu

first: Shefali

last: Patel

first: William

last: Wong

first: Cynthia

last: Indralingam

first: Yi

last: Liu

first: Priscilla

last: Yao

first: Natalie

last: Chiang

first: Taylor

last: Anderson

first: Sara

last: Vandenburgh

first: Jocelyn

last: Olvera

first: Amir

last: Ferry

first: Kennidy

last: Takehara

first: Wenhao

last: Jin

first: Gene

last: Yeo

first: Matthew

last: Tsai

first: Ananda

last: Goldrath


title: BCG-activation of lymphocytes for the generation of donor-independent innate anti-tumor NK and γδ T cells

city: Madrid

first: Enrique

last: Vazquez de Luis

state: Madrid

address: Melchor Fernandez Almagro, 3

country: Spain

institute: CNIC

summary: We performed scRNA-seq to PBMCs incubated with 2 different sub-strains of BCG during 7 days. We found that iBCG co-cultures potently stimulated the proliferation of TRDV2 gamma-delta T cells, while Oncotice did not have the ability to expand this subpopulation, and mainly stimulated NK and classical T cells.

overall_design: mRNA profiles of paired PBMC samples from 3 healthy donors (treated with iBCG or Oncotice) were examined

first: G

last: Esteso

first: M

middle: J

last: Felgueres

first: ÁF

last: García-Jiménez

first: HT

last: Reyburn

first: E

last: Puentes

first: I

last: Murillo

last: Rodríguez

last: Valés-Gómez

last: Vázquez de Luis


title: Interdependent genomic binding of BAP1 and MLL4 regulates a subset of gene expression in HCT116

status: Public on Dec 05 2022

city: Bethesda

first: Kai

last: Ge

state: MD

address: 50 South Dr Rm 4154

department: NIDDK

institute: NIH

summary: Our genomic studies show that ~20% of MLL4 chromatin binding sites overlap with BAP1 binding regions in HCT116 human colon cancer cells. By comparing MLL4 and BAP1 localization in wild type and knockout cells, we show an interdependent genomic binding of MLL4 and BAP1 on MLL4+ BAP1+ enhancers. Profiling of transcriptomes reveals that a small subset of gene expression is co-regulated by MLL4 and BAP1. Together, our findings identify a functional interaction between enhancer H3K4 methyltransferase MLL4 and H2A deubiquitinase.

overall_design: Expression profiling by RNA-Seq in WT, MLL4 KO and BAP1 KO HCT116, and ChIP-Seq profiling of MLL4, BAP1-T7 and H3K4me1

first: Ji

middle: E

last: Lee

first: Zhizhong

last: Ren


title: In Vitro Modeling of CD8 T Cell Exhaustion

status: Public on Dec 01 2022

city: Philadelphia

middle: JOHN

last: WHERRY

address: 421 Curie Blvd,354 BRB II/III

department: Systems Pharmacology       and Translational Therapeutics,Institute for Immunology

institute: University of Pennsylvania


title: Notochord and axial progenitor generation by timely BMP and NODAL inhibition during vertebrate trunk formation

first: Tiago

last: Rito

summary: The formation of the vertebrate body is driven by the progressive and coordinated production of trunk tissues from pools of progenitors located in the posterior of the embryo. Aspects of this process are recapitulated by in vitro models based on pluripotent stem cells (PSCs). However, these models lack several tissue components normally found in the vertebrate trunk. Most strikingly, the notochord, a hallmark of chordates and the source of midline signals that pattern surrounding tissues, is absent from current models of human trunk formation. To investigate how trunk tissue is formed, we performed single-cell transcriptomic analysis of chick embryos. This delineated molecularly discrete progenitor populations, which we spatially locate in the embryo and relate to signalling activity. Guided by this map, we determined how a stereotypical spatial organization of tissue types arises in differentiating human PSCs. This involved LATS1/2 mediated repression of YAP activity facilitating WNT signalling, that, together with FGF mediated ERK1/2 activation, induces the transcription factor Bra/TBXT. In addition, timely inhibition of a WNT-induced NODAL and BMP signalling cascade regulates the proportions of different tissue types produced, including notochordal cells. We exploit this to develop an integrated 3D model of human notochord and neural tissue formation. Together the data provide insight into the mechanisms responsible for the formation of the tissues that comprise the vertebrate trunk and pave the way for future studies of patterning in a tissue-like environment.

overall_design: To investigate the emergence of axial progenitor pools and the trunk tissue they generate, we took advantage of precise staging of chick embryos to select four closely timed stages, approximately 5-6h apart, with somite (S) numbers: 4S, 7S, 10S and 13S (HH8-11, Hamburger Hamilton Stages). Tissue caudal to the third somite pair was dissected and the transcriptome of single cells analysed using the 10X Genomics platform.

first: Ashley

last: Libby

first: Maddy

last: Demuth

first: James

last: Briscoe


title: An Epigenome-Wide Analysis of Socioeconomic Position and Tumor DNA Methylation in Breast Cancer Patients

city: Buffalo

first: Yao

last: Song

address: Carlton House - A349, Elm and Carlton Streets

institute: Roswell Park Comprehensive Cancer Center

summary: Background: Disadvantaged socioeconomic position (SEP), including lower educational attainment and household income, may influence cancer risk and outcomes. We hypothesized that DNA methylation could function as an intermediary epigenetic mechanism that internalizes and reflects the biological impact of SEP.   Methods: Based on tumor DNA methylation data from the Illumina 450K array from 694 breast cancer patients in the Women’s Circle of Health Study, we conducted an epigenome-wide analysis in relation to educational attainment and household income. Functional impact of the identified CpG sites was explored in silico using data from publicly available databases.   Results: We identified 25 CpG sites associated with household income at an array-wide significance level, but none with educational attainment. Two of the top CpG sites, cg00452016 and cg01667837, were in promoter regions of NNT and GPR37, respectively, with multiple epigenetic regulatory features identified in each region. NNT is involved in -adrenergic stress signaling and inflammatory responses, whereas GPR37 is involved in neurological and immune responses. For both loci, gene expression was inversely correlated to the levels of DNA methylation. The associations were consistent between Black and White women, and did not differ by tumor estrogen receptor (ER) status.   Conclusions: In a large breast cancer patient population, we discovered evidence of the significant biological impact of household income on the tumor DNA methylome, including genes in the -adrenergic stress and immune response pathways. Our findings support biological effects of socioeconomic status on tumor tissues which might be relevant to cancer development and progression.

overall_design: Geome-wide methylation assay on HM450 Bead Chip using genomic DNA extracted from formalin-fixed parafilm embedded human breast tumor tissue

first: Jianhong

last: Chen

first: Mark

middle: D

last: Long

first: Sirinapa

last: Sribenja

first: Sung

last: Ma

first: Li

last: Yan

first: Qiang

last: Hu

first: Song

last: Liu

first: Thaer

last: Khoury

first: Chi-Chen

last: Hong

first: Elisa

last: Bandera

first: Anurag

last: Singh

first: Elizabeth

last: Repasky

last: Bouchard

first: Michael

last: Higgins

first: Christine

last: Ambrosone

last: Yao


title: In Vitro Modeling of CD8 T Cell Exhaustion [ATAC-seq]

first: E

last: WHERRY

summary: ATAC-seq was used to study the chromatin landscape of Invitro CD8 T cell exhaustion cells

overall_design: Invitro generated CD8 Tcell subsets were assayed by ATACseq in replicates

first: Jennifer

last: Wu

last: Wherry


title: Small intestine and colon tissue-resident memory CD8+ T cells exhibit transcriptional, epigenetic, and functional heterogeneity in concert with differential dependence on Eomesodermin [CITE-seq]

first: John

last: Chang

overall_design: Performed CITE-seq to unterstand look at heterogeneity

first: Yun

last: Lin

first: Han

last: Duong

first: Abigail

last: Limary

first: Eleanor

middle: S

last: Kim

first: Paul

last: Hsu

first: Shefali

last: Patel

first: William

last: Wong

first: Cynthia

last: Indralingam

first: Yi

middle: C

first: Priscilla

first: Natalie

last: Chiang

first: Taylor

last: Anderson

first: Sara

last: Vandenburgh

first: Jocelyn

last: Olvera

first: Amir

last: Ferry

first: Kennidy

last: Takehara

first: Wenhao

last: Jin

first: Gene

middle: W

last: Yeo

first: Matthew

last: Tsai

first: Ananda

last: Goldrath


title: Single-cell transcriptomic analysis unveils the diversity within mammalian spinal motor neurons

status: Public on Nov 18 2022

city: Taipei

first: Jun-An

last: Chen

address: 128 Academia Road, Section 2

department: Institute of Molecular Biology

country: Taiwan

institute: Academia Sinica

summary: Spinal motor neurons (MNs) integrate sensory stimuli and brain commands to generate movements. In vertebrates, the molecular identities of the cardinal MN types such as those innervating limb versus trunk muscles have been well elucidated. Yet the identities of finer subtypes within these cell populations that innervate individual muscle groups remain enigmatic. Using single-cell transcriptomics, we have investigated heterogeneity in mouse MNs and discovered many unreported MN subtypes. Among limb-innervating MNs, we reveal a surprisingly diverse neuropeptide code for delineating putative motor pool identities. Additionally, we have uncovered that axial MNs are subdivided into three molecularly distinct subtypes, defined by mediolaterally-biased Satb2, Nr2f2 or Bcl11b expression patterns with different axon guidance signatures. These three subtypes are present in chicken and human embryos, suggesting a conserved axial MN expression pattern across higher vertebrates. Overall, our study provides a comprehensive molecular resource of spinal MN types and paves the way towards deciphering how neuronal subtypes evolved to accommodate vertebrate motor behaviors associated with different lifestyles.

overall_design: Single cell RNA seq of e13.5 mouse spinal motor neurons at rostral (brachial and thoracic vertebral segments, from C4 to T3) and caudal (lumbosacral, L1 to S5) segments. Motor neurons were labeled in GFP and sorted via FACS, and loaded onto 10x  Genomics Single Cell 3’ Chip as two samples.

first: J

first: E

last: Liau


title: Granulosa cell mevalonate pathway abnormalities contribute to oocyte meiotic defects and aneuploidy [RNA-seq mouse oocyte]

first: Qian

last: Bian

summary: The mechanisms of oocyte meiotic defects and low competence during ovarian aging remains elusive for decades. Using Hi-C (genome-wide chromatin conformation capture) and Smart RNA-seq of oocytes from 6- weeks or 10- months aged ovaries, the abnormal loose chromatin structures and disturbing expression of meiosis associated genes at metaphase I phase were disclosed. Furthermore, the transcriptomic landscape of granulosa cells (GCs) surrounding oocytes from young and aged ovaries reveled that oocyte meiotic maturation was accompanied with a robust increased expression of genes involved with the mevalonate (MVA) pathway in GCs from young ovaries but these genes expression was not upregulated to counterpart level in GCs from aged ovaries.The inhibitor of MVA pathway of GCs, Statins significantly decreased polar body extrusion rate and increased the rate of irregularly assembled spindles and misaligned chromosomes remarkably in oocytes of culumus-oocyte complex (COCs) from young ovaries . Correspondingly, the activitor of MVA pathway of GCs, Geranylgeraniol ameliorated ovarian reserve and reduced meiotic defects in oocytes of COCs from aged ovaries. Mechanistically, MVA pathway activation in GCs culminated oocyte meiotic maturation by upregulating EGF signaling via LH receptor on GCs surrounding oocytes. Together, MVA pathway is a promising therapeutic target for prompting quality of oocytes from aged ovaries.

overall_design: In this study, the dynamics of chromatin structure of oocytes and the overall transcriptomic landscape of oocytes and GCs throughout oocyte meiosis (growing phase, full-grown phase, metaphase I phase, metaphase II phase) in vivo from young and aged mice were depicted.

first: Lijun

last: Ding

first: Chuanming

last: Liu

first: Wu

last: Zuo


title: Transient Polycomb activity represses developmental genes in growing oocytes.

status: Public on Jan 11 2023

city: Clayton

first: Patrick

last: Western

state: VIC

address: 27-31 Wright Street

department: Centre for Reproductive Health

country: Australia

institute: Hudson Institute of Medical Research

summary:
Background: Non-genetic disease inheritance and offspring phenotype is substantially influenced by germline epigenetic programming, including genomic imprinting. Loss of Polycomb Repressive Complex 2 (PRC2) function in oocytes causes non-genetically inherited effects on offspring, including embryonic growth restriction followed by post-natal offspring overgrowth. While PRC2 dependent non-canonical imprinting is likely to contribute, less is known about germline epigenetic programming of non-imprinted genes during oocyte growth. In addition, de novo germline mutations in genes encoding PRC2 lead to overgrowth syndromes in human patients, but the extent to which PRC2 activity is conserved in human oocytes is poorly understood.
Results: In this study we identify a discrete period of early oocyte growth during which PRC2 is expressed in mouse growing oocytes. Deletion of Eed during this window led to the de-repression of 343 genes. A high proportion of these were developmental regulators, and the vast majority were not imprinted genes.  Many of the de-repressed genes were also marked by the PRC2-dependent epigenetic modification histone 3 lysine 27 trimethylation (H3K27me3) in primary-secondary mouse oocytes, at a time concurrent with PRC2 expression. In addition, we found H3K27me3 was also enriched on many of these genes by the germinal vesicle (GV) stage in human oocytes, strongly indicating that this PRC2 function is conserved in the human germline. However, while the 343 genes were de-repressed in mouse oocytes lacking EED, they were not de-repressed in pre-implantation embryos and lost H3K27me3 during pre-implantation development. This implies that H3K27me3 is a transient feature that represses a wide range of genes in oocytes. Conclusions: Together, these data indicate that EED has spatially and temporally distinct functions in the female germline to repress a wide range of developmentally important genes, and that this activity is conserved in the mouse and human germlines.

overall_design: Examination of the impact of EED deletion in oocytes on oocyte transcription

first: Ellen

last: Jarred

first: Zhipeng

last: Qu

first: Tesha

first: Ruby

last: Oberin

first: Sigrid

last: Petautschnig

first: Heidi

last: Bildsoe

first: Stephen

last: Pederson

first: Qing-hua

last: Zhang

first: Jessica

middle: M

last: Stringer

first: John

last: Carroll

first: David

middle: K

last: Gardner

first: Maarten

last: van den Buuse

first: Natalie

last: Sims

first: William

middle: T

last: Gibson

last: Adelson


title: Characterization of human plasma pregnancy-associated miRNAs at first trimester and their association with pregnancy complications [cohort 2]

status: Public on Nov 03 2022

city: Chicoutimi

first: Luigi

last: Bouchard

state: Quebec

address: 305 rue Saint-Vallier, Pavillon des Augustines

department: Biochimie et génomique fonctionnelle

country: Canada

institute: Université de Sherbrooke

summary: To characterize the human plasma microtranscriptome profile at first trimester of pregnancy in presence or not of pregnancy complications, we sequenced microRNAs in plasma samples collected from pregnant women between the 6th and the 15th weeks of pregnancy as a replication cohort. We then performed differential expression analyses to assess the miRNA profile diffrences according to the presence of pregnancy complications or not (i.e. Gestational diabetes mellitus, Gestational hypertension or preeclampsia vs. normal pregnancies).

overall_design: Complete microtransciptome from 328 plasma samples colletected between the 6th and the 15th weeks of pregnancy in women (316 biological replicates, 12 technical replicates) was assess by next-generation sequencing as a replication cohort for the Gen3G cohort. Women were from European descent.

first: Marie-France

last: Hivert

first: Patrice

last: Perron

first: Renée

last: Guérin

first: Véronique

last: Desgagné

first: Cécilia

last: Légaré

first: Andrée-Anne

last: Clément

first: Kathrine

last: Thibeault

first: Pierre-Étienne

last: Jacques

first: Michelle

last: Scott

first: Frédérique

last: White

last: Fraser

first: Zhong

last: Luo


title: Protein farnesylation is involved in the adaptation of Arabidopsis to nitrogen starvation

last: BRUNAUD

summary: ngs2020_24_era-nitrogen-What genes are affected in the era1 mutant compared to the WT?-Characterize the effect of nitrogen nutrition (0 mM, 2mM and 10 mM NH4NO3) on development and metabolism in era1 and WT at the rosette stage at the onset of flower bud. Library construction with Quantseq 3seq sequencing

overall_design: 18 samples with 3 biological replicats. dose response,genotype and ecotype comparison

first: Olivier

last: Pichon

first: Léo

last: Bellenger

first: Alexandra

last: Launay-Avon

first: Etienne

last: Delannoy


title: Characterization of human plasma pregnancy-associated miRNAs at first trimester and their association with pregnancy complications

status: Public on Nov 01 2022

last: Bouchard


title: Characterization of human plasma pregnancy-associated miRNAs at first trimester and their association with pregnancy complications [cohort 1]

status: Public on Oct 24 2022

summary: To characterize the human plasma microtranscriptome profile at first trimester of pregnancy in presence or not of pregnancy complications, we sequenced microRNAs in plasma samples collected from pregnant women between the 4th and the 16th weeks of pregnancy. We then performed differential expression analyses to assess  the miRNA profile diffrences according to the presence of pregnancy complications or not (i.e. Gestational diabetes mellitus, Gestational hypertension or preeclampsia vs. normal pregnancies).

overall_design:
Complete microtransciptome from 456 plasma samples colletected between the 4th and the 16th weeks of pregnancy in women (444 biological replicates, 12 technical replicates) was assess by next-generation sequencing. Women were from European descent and plasma samples were collected 1 hour post a 50g glucose challenge test. Out of the 444 pregnant women, 377 (corresponding to 386 samples combining biological and technical replicates) consented to data sharing.
The 'Pregnancy Status 1' sample characteristics field contains the pregnancy status of the women. If a second pregnancy status was also present, it is recorded in the 'Pregnancy Status 2'.

last: Hivert

last: Perron

first: Cédrik

last: Poirier


title: effecaps-phytophthora capsici project: Phytophthora capsici Illumina RNAseq transcriptome of two isolates, one adapted to pepper, another non adapted, in two pepper accessions, one partially resistant and one susceptible to Phytophthora capsici

summary: ngs2013_07_pcapsici-effecaps-phytophthora capsici-The analysed RNAseq concerned the oomycete Phytophthora capsici in growth on pepper plants. 1/ How the adaptation of a pathogen to a host depends on its gene expression? 2/ How the plant host impacts the expression of pathogen genes at the very beginning of infection?-Two isolates of Phytophthora capsici were used: the Pc107 isolate (called A for adapted to pepper from INRAE GAFL Avignon), and the Pc273 isolate (N for non-adapted to pepper, collected on pumpkin in the USA). Two accessions of pepper (Capsicum annuum L., the host) were used: Yolo Wonder (YW, PM0031), susceptible (S) to Phytophthora capsici, and Criollo de Morelos 334 (CM334, PM0702), partially resistant (R). Inoculations were performed, as described in Lefebvre and Palloix (1996), by putting on the wounded stem a plug of mycelium. Inoculated plants were transferred to a growth chamber at 24°C/22°C temperature on a 12h/12h light/dark cycle. At 24 hours-post-inoculation, 12 total RNA samples were extracted from inoculated plants for the 4 host-isolate interactions: R_A, S_A, R_N and S_N. Each sample consisted of six pooled stem fragments. The stem fragments are the 5-mm region immediately under the visible stem necrosis. Samples were flash-frozen in liquid-nitrogen and stored at -80ºC. They were ground in liquid nitrogen with a cold mortar and pestle. Total RNA was extracted using QIAGEN Rneasy Plant Mini Kit. RNA-seq libraries were constructed at IPS2 POPS platform (France) by TruSeq_Stranded_mRNA_SamplePrep_Guide_15031047_D protocol (Illumina®, California, USA). Sequencing was conducted on an Illumina Hiseq2000 hosted by Genoscope (Evry, France). The RNA-seq samples have been sequenced in paired-end (PE) with a sizing of 260 bp and a read length of 100 bases, lane repartition and barcoding giving approximately 35 million of paired-end reads per sample.

overall_design: 24 samples with 3 biological replicats. genotype comparison,treated vs untreated comparison

first: Veronique

last: Brunaud

last: Lefebvre

first: Sandrine

last: Balzergue


title: The cortical thymic epithelial cell compartment is shaped by stage-specific thymocyte crosstalk which drives loss of Foxn1 and its key target genes

status: Public on Oct 28 2022

city: Oxford

first: Adam

last: Handel

address: John Radcliffe Hospital

department: Weatherall Institute of Molecular Medicine

institute: University of Oxford

summary: In the thymus, cortical and medullary thymic epithelial cells (TEC) support the production of abT-cells from bone marrow-derived progenitors. For cortical TEC (cTEC), the expression a specialised gene signature that encodes multiple key regulators including CXCL12, Delta-like 4 (DLL4) and b5t enables the cortex to support T-lineage commitment, and the generation and selection of CD4+CD8+ thymocytes. While the importance of the cTEC in T-cell development are well defined, the mechanisms that shape the cTEC compartment and maintain its functional specialisation are unclear. Using CXCL12DsRed reporter mice, we show that changes in expression of the chemokine CXCL12 reveal a developmentally regulated programme of cTEC heterogeneity. While cTEC uniformly express CXCL12 during neonatal stages, progression through postnatal life triggers the appearance of CXCL12- cTEC subset that continues to reside in the cortex. We show the appearance of CXCL12- cTEC is influenced by the maturation of CD4-CD8-, but not CD4+CD8+ thymocytes, demonstrating stage-specific thymocyte crosstalk controls cTEC heterogeneity. Importantly, while fate mapping experiments show that both CXCL12+ and cTEC12- cTEC arise from cells expressing Foxn1, RNA sequencing analysis shows they are genetically distinct. Thus, CXCL12- cTEC lack Foxn1 expression, which directs loss of the Foxn1-dependent cTEC gene signature that may explain the reduced capacity of CXCL12- cTEC for thymocyte interactions. In sum, our study shows that shaping of cTEC compartment during the life-course occurs via stage-specific thymocyte crosstalk which drives loss of Foxn1 and its key target genes, that may then determine the functional competence of the thymic cortex.

overall_design: RNA-seq in Cxcl12DsRed+ and Cxcl12DsRed- cTEC

first: Andrea

first: Graham

last: Anderson


title: Comparison of small RNA Profiles of extracellular vesicles (EVs) derived from three mesenchymal stem cell-laden Matrigel composites

status: Public on Oct 17 2022

city: Shen Zhen

first: Shaohua

last: Ma

state: Guangdong Province

address: nanshan street

institute: Tsinghua University

summary: To investigate the difference of small RNA profiles of EVs derived from mesenchymal stem cell-laden Matrigel composites: high cell density beads (HDB) , low cell density beads (LDB) , and high cell density bulk ge (HDG)

overall_design: We collected EVs from three mesenchymal stem cell-laden Matrigel composites. The small RNA sequencing was performed by BGI-Shenzhen, China.

first: Jiayi

last: Tan


title: Single cell transcriptional and chromatin accessibility profiling identify the cellular heterogeneity of human medulloblastoma

status: Public on Oct 08 2022

city: Cincinnati

first: Zaili

last: Luo

state: OH

address: 3333 Burnet Ave.

institute: CCHMC

summary: We report the application of single-molecule-based sequencing technology for high-throughput profiling of chromosome occupation and single cell gene expression or single nuclei chromatin accessibility in medulloblastoma tissues or cells. To further define the cellular identity at the single cell level, we characterized 26 MB tissues including 18 newly diagnosed MB tumor tissues by single cell scRNA-seq and scATAC-seq (the assay for transposase-accessible chromatin-sequencing) together with 8 previously reported MB single cell transcriptomics. The newly diagnosed MB tumors included four SHH-MBs (45,731 cells), nine G3-MBs (82,834 cells), thirteen G4 MBs (77,521 cells) with a median of 7,926 cells for scRNA-seq and 9,342 cells for scATAC-seq per MB tumor, respectively. To decipher how dynamic accessibility at the cis-regulatory elements (CREs) relates to the gene regulatory program in TCP-like cells from G3- and G4- MBs, we performed single nuclei ATAC-seq (snATAC-seq) to determine the single-cell chromatin accessibility landscape using high-quality nuclei from a set of fresh G3 and G4 MB tumors that matched with scRNA-seq. Finally, we show that gene expression with chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. Our studies identified a human-specific intermediate progenitor population important for cerebellar neural lineage development and the growth and metastasis of aggressive MBs, highlighting potential therapeutic targets.

overall_design:
Examination of single cell transcriptional and ATAC profiling in 3 human medulloblastoma tissues. Cut&run of 4 antibody for 2 cells
To comprehensively explore the 3D genome architecture of human aggressive medulloblastomas and to assess the contributions of genome architecture to transcriptional regulation across subgroups, we performed comparative analyses of high-throughput chromosome conformation capture (Hi-C) in medulloblastoma patient derived tumor cells, including Group 3 MB cells MB-004 and Group 4 MB cells UPN3550. We performed the Hi-C experiments in these 2 cells

Please note that the processed data file (along with the data processing description) has been updated for the GSM5952337 sample on April 26, 2023.

first: Chuntao

last: Zhao

first: Dazhuan

last: Xin

first: Q

last: Lu


title: Single Cell and Spatial Sequencing Characterizes Cell Type Composition and Cell-Cell Interaction in Psoriasis

status: Public on Sep 20 2022

city: Los Angeles

first: Feiyang

state: CA

address: 610, Charles Young Dr East, TLSB 3000C

department: Molecular Biology Institute

institute: UCLA

summary: The immunopathogenesis of psoriasis, a common chronic inflammatory disease of the skin, is still incompletely understood. Here we demonstrate, using a combination of single-cell and spatial-sequencing, that psoriatic fibroblasts, a hitherto unappreciated participant in psoriasis pathogenesis, contribute to the immune network in psoriasis through transition to a pro-inflammatory state characterized by CCL19 and CCL13. Fibroblasts interact with three other main cell-types that are in close proximity: keratinocytes, T cells and myeloid cells, that also interact with each other. In addition, our data demonstrates striking compartmentalization of inflammatory responses in distinct layers of the psoriatic epidermis, including IL-17A responses and autocrine IL-36 autoinflammatory activity within the supraspinous layer. Lastly, our data defined the T cell and myeloid populations involved in psoriasis, including enrichment of CD8+ IL17A expressing T cells, CD16+ dendritic cells, and LAMP3+ dendritic cells. These data provide an unprecedented view of psoriasis pathogenesis, which expands our understanding of the critical cellular players to include inflammatory fibroblasts as well as their cell-cell interactions, defines the spatial compartmentalization of specific inflammatory processes, together a unique resource for future investigations.

overall_design: To study cell type compositon and transcription changes in normal skin from healthy donors, peripheral normal skin from psoriasis patients and psoriatic skin from psoriasis patients

first: Matteo

last: Pellegrini

first: Robert

last: Modlin

first: Johann

last: Gudjonsson


title: Identification of Novel Biomarkers of Bronchopulmonary Dysplasia model

status: Public on Aug 29 2022

city: Shenyang

first: Jianhua

last: Fu

address: 36 Sanhao Street

institute: China medical university

summary: In order to study the gene expression changes in neonatal bronchopulmonary dysplasia (BPD) induced by hyperoxia, we used a rat model to detect the gene expression changes in the control group (A) and hyperoxia group (O) after birth.

overall_design: We used RNA-Seq data of BPD and healthy control rats from our previous studies, wherein data from 30 samples was collected at days 1, 3, 7, 10, and 14. Data for preprocessing analysis included 17,613 differentially expressed genes (DEGs) with false discovery rate < 0.05 and log2 fold change ≥ 0.5.

first: Xuefei

last: Yu


title: ChIP-seq and RNA-seq data for Glioma

status: Public on Sep 22 2022

city: Rochester

first: ARIJIT

last: PANDA

state: MINNESOTA

address: 200 1st street SW

institute: MAYO CLINIC

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

overall_design:
Refer to individual Series

Please note that the records have been updated with the sample annotation files (RNA_CHIP_Seq_deidentify.csv, data_dictionary.xlsx) on Apr 4, 2025.


title: Assessment of chromatin remodeling of acute myeloid leukemia cells treated with gilteritinib

status: Public on Aug 09 2022

city: Iwaki

first: Jinichi

last: Mori

state: Fukushima

address: 57, Jyoban kamiyunagayamachi kaminodai

institute: Jyoban Hospital Tokiwa Foundation

summary: Gilteritinib is a FLT3 inhibitor that has been approved  for relapsed acute myeloid leukemia (AML) carrying FLT3 mutations. However,  the effects of this drug on chromatin remodeling of AML cells remains unknown. We tested the state of chromatin openness of AML cells obtained from a patient before and after treatment with gilteritinib using Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq).

overall_design: Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) for 2 AML cell samples: before and after.

first: J

first: T

last: Sawada

first: M

last: Nojiri

last: Okada

last: Kurokawa

first: S

last: Kato


title: Expression data from postmortem human dorsolateral prefrontal cortex - psychiatric disorders & healthy controls

status: Public on Nov 17 2022

city: Neuherberg

first: Karolina

last: Worf

address: Ingolstaedter Landstr. 1

department: Computational Health

institute: Helmholtz Zentrum Muenchen

summary: In psychiatric disorders, common and rare genetic variants cause widespread dysfunction of cells and their interactions, especially in the prefrontal cortex, giving rise to psychiatric symptoms. To better understand these processes, we traced the effects of common and rare genetics, and cumulative disease risk scores, to their molecular footprints in human cortical single-cell types. We demonstrated that examining gene expression at single-exon resolution is crucial for understanding the cortical dysregulation associated with diagnosis and genetic risk derived from common variants. We then used disease risk scores to identify a core set of genes that serve as a footprint of common and rare variants in the cortex. Pathways enriched in these genes included dopamine regulation, circadian entrainment, and hormone regulation. Single-nuclei-RNA-sequencing pinpointed these enriched genes to excitatory cortical neurons. This study highlights the importance of studying sub-gene-level genetic architecture to classify psychiatric disorders based on biology rather than symptomatology, to identify novel targets for treatment development.

overall_design: Profiles of gene expression based on resolution of single exons of postmortem dorsolateral prefrontal cortex (DLPFC) of Brodmann area 9 (BA 9) from 169 adult subjects aged 18-87 years with schizophrenia (SCZ; n = 68), bipolar disorder (BD; n = 15), and major depressive disorder (MDD; n = 24) and matched controls (n = 62). Replicates were removed. Demographic, clinical, and pharmacologic data were collected as part of a medical history survey using the Diagnostic Instrument for Brain Studies (DIBS). Samples were hybridized to Affymetrix Human Exon 1.0 ST v2 arrays.

first: Natalie

last: Matosin

first: Nathalie

last: Gerstner

first: Anna

last: Froehlich

last: Koller

first: Franziska

last: Degenhardt

first: Holger

last: Thiele

first: Marcella

last: Rietschel

first: Madhara

last: Udawela

first: Elisabeth

last: Scarr

first: Brian

last: Dean

first: Fabian

last: Theis

first: Janine

last: Knauer-Arloth

first: Nikola

last: Mueller


title: Paired bulk and single-cell RNA-seq on high-grade serous ovarian cancer (HGSOC) samples

status: Public on Nov 13 2022

first: Ariel

middle: A

last: Hippen

address: 3400 Civic Center Blvd

summary: We have sequenced ovarian tumors in several different ways: 1) poly-A captured scRNA-seq, 2) poly-A captured pooled scRNA-seq in pools of 4 samples each 3) Bulk RNA-seq on ribo-depleted tumor chunks 4) Bulk RNA-seq on poly-A captured dissociated cells 5) Bulk RNA-seq on ribo-depleted dissociated cells

overall_design:
Gene expression was measured at both the bulk and single-cell level for HGSOC samples from separate, unrelated individuals. The initial dataset contains 34 samples from 8 individuals.
***Raw data are being deposited in dbGaP due to patient privacy concerns***

first: Dalia

last: Omran

first: Lukas

last: Weber

first: Jennifer

last: Doherty

first: Stephanie

last: Hicks

first: Casey

last: Greene


title: Cell cycle arrest of neural progenitors causes impaired dopaminergic neuronal differentiation in GBA associated Parkinson’s disease midbrain organoids [1]

status: Public on Jul 24 2022

city: Belvaux

first: Enrico

last: Glaab

state: Capellen

address: 6, avenue du Swing

country: Luxembourg

institute: University of Luxembourg

summary: The mechanisms underlying Parkinson's disease (PD) etiology are only partially understood despite intensive research conducted in the field. Recent evidence suggests that early neurodevelopmental defects might play a role in cellular susceptibility to neurodegeneration. To study the early developmental contribution of GBA mutations in PD we used patient-derived iPSCs carrying a heterozygous N370S mutation in the GBA gene. Patient-specific midbrain organoids displayed GBA-PD relevant phenotypes such as reduction of GCase activity, autophagy impairment and mitochondrial dysfunction. Genome-scale metabolic (GEM) modeling predicted changes in lipid metabolism which were validated with lipidomics analysis, showing significant differences in the lipidome of GBA-PD. In addition, patient-specific midbrain organoids exhibited an increase in the neural progenitor population showing signs of cellular senescence. This was accompanied by a decrease in the number and complexity of dopaminergic neurons. These results provide insights into how GBA mutations may lead to neurodevelopmental defects thereby predisposing to PD pathology.

overall_design: Comparative gene expression profiling analysis of RNA-seq data from GBA-PD patient-derived organoids and control organoids

first: Isabel

last: Rosety

first: Alise

last: Zagare

first: Claudia

last: Saraiva

first: Sarah

last: Nickels

first: Paul

last: Antony

first: Catarina

last: Almeida

first: Rashi

last: Halder

first: Sergiy

last: Velychko

first: Thomas

last: Rauen

first: Hans

last: R Scholer

first: Silvia

last: Bolognin

last: Sauter

first: Javier

last: Jarazo

first: Rejko

last: Krueger

first: Jens

last: C Schwamborn