Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell Architecture and Functional Requirement of Alternative Splicing during Hematopoietic Stem Cell Emergence

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

ORGANISM(S): Mus musculus

PROVIDER: GSE185555 | GEO | 2021/10/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation.

Project description:Single-cell transcriptional profiling has rapidly advanced our understanding of the embryonic hematopoiesis; however, whether and what role RNA alternative splicing (AS) plays remains an enigma. This is important for understanding the mechanisms underlying splicing-associated hematopoietic diseases and for the derivation of therapeutic stem cells. Here, we used single-cell full-length transcriptome data to construct an isoform-based transcriptional atlas of the murine endothelial-to-hematopoietic stem cell (HSC) transition, which enables the identification of hemogenic signature isoforms and stage-specific AS events. We showed that the inclusion of these hemogenic-specific AS events was essential for hemogenic function in vitro. Expression data and knockout mouse studies highlighted the critical role of Srsf2: Early Srsf2 deficiency from endothelial cells affected the splicing pattern of several master hematopoietic regulators and significantly impaired HSC generation. These results redefine our understanding of the dynamic HSC developmental transcriptome and demonstrate that elaborately controlled RNA splicing governs cell fate in HSC formation.

| S-EPMC8741192 | biostudies-literature

Single-cell Architecture and Functional Requirement of Alternative Splicing during Hematopoietic Stem Cell Emergence [RNA-Seq]

Project description:Hematopoietic stem cells (HSCs) are well known to generate from a rare hemogenic population of embryonic endothelial cells through a dynamic fate transition, accompanied by widespread changes in gene regulatory networks. Nevertheless, RNA splicing, a striking feature in shaping transcriptome and enabling the generation of vast transcripts and diverse proteins, has never been illustrated in this transient endothelial to HSC conversion. Here, we constructed an isoform-based transcriptome landscape during HSC development at single-cell resolution, which enables the identification of hemogenic signature isoforms, as well as stage-specific splicing events. Combining with functional screening, we showed that the inclusion of such hemogenic-specific exons was essential for hemogenic function in vitro. Moreover, their gradual appearance along with HSC specification from endothelial cells was orchestrated by the splicing regulator Srsf2. Therefore, early Srsf2 deficiency from endothelia cells dramatically impaired the HSC generation, which was accompanied by changes in the splicing pattern of several master hematopoietic regulators. These results redefine our understanding of the dynamic transcriptome diversity and demonstrate that the elaborate control of splicing governs cell fate in HSC formation.

2023-10-01 | GSE185554 | GEO

Single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation

Project description:Hematopoietic stem cells (HSCs) are well known to generate from a rare hemogenic population of embryonic endothelia cells through a dynamic fate transition, accompanied by widespread changes in gene regulatory networks. Nevertheless, RNA splicing, a striking feature in shaping transcriptome and enabling the generation of vast transcripts and diverse proteins, has never been illustrated in this transient endothelial to HSC conversion. Here, we constructed an isoform-based transcriptome landscape during HSC development at single-cell resolution, which enables the identification of hemogenic signature isoforms, as well as stage-specific splicing events. Combining with functional screening, we showed that the inclusion of such hemogenic-specific exons was essential for hemogenic function in vitro. Moreover, their gradual appearance along with HSC specification from endothelia cells was orchestrated by the splicing regulator Srsf2. Therefore, early Srsf2 deficiency from endothelia cells dramatically impaired the HSC generation, which was accompanied by changes in splicing pattern of several master hematopoietic regulators. These results redefine our understanding of the dynamic transcriptome diversity and demonstrate that the elaborate control of splicing governs cell fate in HSC formation.

2021-10-13 | GSE153653 | GEO

Single-cell Architecture and Functional Requirement of Alternative Splicing during Hematopoietic Stem Cell Emergence

Project description:Single-cell Architecture and Functional Requirement of Alternative Splicing during Hematopoietic Stem Cell Emergence

| PRJNA769627 | ENA

Single-cell Architecture and Functional Requirement of Alternative Splicing during Hematopoietic Stem Cell Emergence [RNA-Seq]

Project description:Single-cell Architecture and Functional Requirement of Alternative Splicing during Hematopoietic Stem Cell Emergence [RNA-Seq]

| PRJNA769638 | ENA

Single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation

Project description:Single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation

| PRJNA643551 | ENA

Clonal analysis reveals remarkable functional heterogeneity during hematopoietic stem cell emergence.

Project description: Not available

| S-EPMC5539347 | biostudies-literature

Single-Cell Alternative Splicing Analysis with Expedition Reveals Splicing Dynamics during Neuron Differentiation.

Project description:Alternative splicing (AS) generates isoform diversity for cellular identity and homeostasis in multicellular life. Although AS variation has been observed among single cells, little is known about the biological or evolutionary significance of such variation. We developed Expedition, a computational framework consisting of outrigger, a de novo splice graph transversal algorithm to detect AS; anchor, a Bayesian approach to assign modalities; and bonvoyage, a visualization tool using non-negative matrix factorization to display modality changes. Applying Expedition to single pluripotent stem cells undergoing neuronal differentiation, we discover that up to 20% of AS exons exhibit bimodality. Bimodal exons are flanked by more conserved intronic sequences harboring distinct cis-regulatory motifs, constitute much of cell-type-specific splicing, are highly dynamic during cellular transitions, preserve reading frame, and reveal intricacy of cell states invisible to conventional gene expression analysis. Systematic AS characterization in single cells redefines our understanding of AS complexity in cell biology.

| S-EPMC5540791 | biostudies-literature

Functional requirement of alternative splicing in epithelial-mesenchymal transition of pancreatic circulating tumor.

Project description:Circulating tumor cells (CTCs) that undergo epithelial-to-mesenchymal transition (EMT) can provide valuable information regarding metastasis and potential therapies. However, current studies on the EMT overlook alternative splicing. Here, we used single-cell full-length transcriptome data and mRNA sequencing of CTCs to identify stage-specific alternative splicing of partial EMT and mesenchymal states during pancreatic cancer metastasis. We classified definitive tumor and normal epithelial cells via genetic aberrations and demonstrated dynamic changes in the epithelial-mesenchymal continuum in both epithelial cancer cells and CTCs. We provide the landscape of alternative splicing in CTCs at different stages of EMT, uncovering cell-type-specific splicing patterns and splicing events in cell surface proteins suitable for therapies. We show that MBNL1 governs cell fate through alternative splicing independently of changes in gene expression and affects the splicing pattern during EMT. We found a high frequency of events that contained multiple premature termination codons and were enriched with C and G nucleotides in close proximity, which influence the likelihood of stop codon readthrough and expand the range of potential therapeutic targets. Our study provides insights into the EMT transcriptome's dynamic changes and identifies potential diagnostic and therapeutic targets in pancreatic cancer.

| S-EPMC10869908 | biostudies-literature

The human XPG gene: gene architecture, alternative splicing and single nucleotide polymorphisms.

Project description:Defects in the XPG DNA repair endonuclease gene can result in the cancer-prone disorders xeroderma pigmentosum (XP) or the XP-Cockayne syndrome complex. While the XPG cDNA sequence was known, determination of the genomic sequence was required to understand its different functions. In cells from normal donors, we found that the genomic sequence of the human XPG gene spans 30 kb, contains 15 exons that range from 61 to 1074 bp and 14 introns that range from 250 to 5763 bp. Analysis of the splice donor and acceptor sites using an information theory-based approach revealed three splice sites with low information content, which are components of the minor (U12) spliceosome. We identified six alternatively spliced XPG mRNA isoforms in cells from normal donors and from XPG patients: partial deletion of exon 8, partial retention of intron 8, two with alternative exons (in introns 1 and 6) and two that retained complete introns (introns 3 and 9). The amount of alternatively spliced XPG mRNA isoforms varied in different tissues. Most alternative splice donor and acceptor sites had a relatively high information content, but one has the U12 spliceosome sequence. A single nucleotide polymorphism has allele frequencies of 0.74 for 3507G and 0.26 for 3507C in 91 donors. The human XPG gene contains multiple splice sites with low information content in association with multiple alternatively spliced isoforms of XPG mRNA.

| S-EPMC31292 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data