Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeted CRISPR-Cas9 screening identifies core transcription factors controlling murine haemato-endothelial fate commitment [SORT-seq]

ABSTRACT: During development, blood generation begins in the yolk sac with the differentiation of haemato-endothelial mesoderm generating haematopoietic progenitors. This study aimed to identify the crucial molecular regulators of haemato-endothelial mesoderm formation and to extend our knowledge of the process in an unbiased way. We employed a murine embryonic stem cell model that recapitulates embryonic blood development, and performed targeted CRISPR-Cas9 knock out screens focusing on transcription factors and chromatin regulators, which highlighted the transcription factors Smad1, Ldb1, Six4 and Zbtb7b. Embryonic stem cells lacking these regulators gave rise to mesodermal subsets with a defined lineage differentiation bias, while transcriptome analysis of these cells uncovered the precise impact of each factor on gene expression in the developing mesoderm. Our study reveals novel molecular pathways governing mesodermal development crucial to allow endothelial and haematopoietic lineage specification and paves the way for future advances in haematopoietic stem cell applications.

ORGANISM(S): Mus musculus

PROVIDER: GSE302880 | GEO | 2025/10/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Targeted CRISPR-Cas9 screening identifies core transcription factors controlling murine haemato-endothelial fate commitment [RNA-seq]

Project description:During development, blood generation begins in the yolk sac with the differentiation of haemato-endothelial mesoderm generating haematopoietic progenitors. This study aimed to identify the crucial molecular regulators of haemato-endothelial mesoderm formation and to extend our knowledge of the process in an unbiased way. We employed a murine embryonic stem cell model that recapitulates embryonic blood development, and performed targeted CRISPR-Cas9 knock out screens focusing on transcription factors and chromatin regulators, which highlighted the transcription factors Smad1, Ldb1, Six4 and Zbtb7b. Embryonic stem cells lacking these regulators gave rise to mesodermal subsets with a defined lineage differentiation bias, while transcriptome analysis of these cells uncovered the precise impact of each factor on gene expression in the developing mesoderm. Our study reveals novel molecular pathways governing mesodermal development crucial to allow endothelial and haematopoietic lineage specification and paves the way for future advances in haematopoietic stem cell applications.

2025-10-12 | GSE302791 | GEO

Targeted CRISPR-Cas9 screening identifies core transcription factors controlling murine haemato-endothelial fate commitment

2025-10-12 | GSE287036 | GEO

Expression data from undifferentiated human embryonic stem cells (hESC) and Day 3.5 mesodermal progenitor (CD326neg CD56+) population

Project description:Our understanding of how mesodermal tissue is formed, has been limited by the absence of specific and reliable markers of early mesoderm commitment. We report that mesoderm commitment from human embryonic stem cells (hESC) is initiated by Epithelial to Mesenchymal transition (EMT) as shown by gene expression profiling and by reciprocal changes in expression of the cell surface proteins, EpCAM/CD326 and NCAM/CD56. Molecular and functional assays reveal that CD326negCD56+ cells, generated from hESC in the presence of activin A, BMP4, VEGF and FGF2, represent a novel, multi-potent mesoderm-committed progenitor population. CD326negCD56+ progenitors are unique in their ability to generate all mesodermal lineages including hematopoietic, endothelial, mesenchymal (bone, cartilage, fat, fibroblast), smooth muscle and cardiomyocytes, while lacking the pluripotency of hESC. CD326negCD56+ cells are the precursors of previously reported, more lineage-restricted mesodermal progenitors. These findings present a novel approach to study how germ layer specification is regulated, and offer a unique target for tissue engineering. We used microarrays to compare gene expression profile of early mesodermal progenitors with undifferentiated hESC (H9 line). Mesoderm induction from hESC was initiatiated with combination of morphogens and growth factors including activin A, bone morphogenic protein 4, basic fibroblast growth factor and vascular endothelial growth factor. Proposed mesodermal progenitor population was isolated by FACS on day 3.5 of culture based on the presence of CD56 expression and the absenbce of CD326 expression.

2010-05-27 | E-GEOD-21668 | biostudies-arrayexpress

Chromatin accessibility landscape upon induction of Msgn1, Pax3 and Myf5 in mesodermal cells and identification of conserved Pax3 binding sites and target genes during skeletal myogenesis

Project description:The transcriptional mechanisms driving lineage specification during development are still largely unknown as the interplay of multiple transcription factors makes it difficult to dissect these molecular events. Using a cell-based differentiation platform to probe transcription function, we investigated the role of the key paraxial mesoderm and skeletal myogenic commitment factors, Msgn1, Tbx6, Foxc1, Pax3, Paraxis, Meox1, Six1 and Myf5, in paraxial mesoderm and skeletal myogenesis. From this study, we define a genetic hierarchy, with Pax3 emerging as the gatekeeper between the presomitic mesoderm and the myogenic lineage. By assaying chromatin accessibility, genomic binding and transcription profiling in mesodermal cells from mouse and human Pax3-induced embryonic stem cells and Pax3-null E9.5 mouse embryos, we identified conserved Pax3 functions in the activation of the skeletal myogenic lineage through modulation of Hedgehog, Notch, and BMP signaling pathways. In addition, we demonstrate that Pax3 molecular function involves chromatin remodeling of its bound elements through an increase in chromatin accessibility and cooperation with Six4 and Tead2 factors. Together, our data provide the first integrated analysis of Pax3 function, demonstrating its ability to remodel chromatin in mesodermal cells from developing embryos and proving a mechanistic footing for the transcriptional hierarchy driving myogenesis.

2019-02-26 | GSE125203 | GEO

Expression data from undifferentiated human embryonic stem cells (hESC) and Day 3.5 mesodermal progenitor (CD326neg CD56+) population

2010-05-06 | GSE21668 | GEO

A trio of bipotent precursors seeds the mesenchymal, haematopoietic, and endothelial lineages of the yolk sac

Project description:During embryogenesis, haematopoietic and endothelial lineages emerge closely in time and space. It is thought that the first blood and endothelium derive from a common clonal ancestor, the haemangioblast. However, investigation of candidate haemangioblasts in vitro has revealed a mesenchymal differentiation potential, a feature more compatible with an earlier mesodermal precursor. To date, no evidence for an in vivo haemangioblast has been discovered. Using single cell RNA-Sequencing and in vivo cellular barcoding, we have unraveled the ancestral relationships that give rise to the haematopoietic lineages of the yolk sac, the endothelium, and the mesenchyme. We show that the mesodermal derivatives of the yolk sac are produced by three distinct bipotential precursors: the haemangioblast, mesenchymoangioblast, and a novel cell type: the haematomesoblast. Between E6.5 and E7.5, this trio of precursors seeds haematopoietic, endothelial, and mesenchymal trajectories.

2022-12-21 | GSE204896 | GEO

In vivo clonal tracking reveals evidence of haemangioblast and haematomesoblast contribution to yolk sac haematopoiesis

Project description:During embryogenesis, haematopoietic and endothelial lineages emerge closely in time and space. It is thought that the first blood and endothelium derive from a common clonal ancestor, the haemangioblast. However, investigation of candidate haemangioblasts in vitro revealed the capacity for mesenchymal differentiation, a feature more compatible with an earlier mesodermal precursor. To date, no evidence for an in vivo haemangioblast has been discovered. Using single cell RNA-Sequencing and in vivo cellular barcoding, we have unraveled the ancestral relationships that give rise to the haematopoietic lineages of the yolk sac, the endothelium, and the mesenchyme. We show that the mesodermal derivatives of the yolk sac are produced by three distinct precursors with dual-lineage outcomes: the haemangioblast, the mesenchymoangioblast, and a previously undescribed cell type: the haematomesoblast. Between E5.5 and E7.5, this trio of precursors seeds haematopoietic, endothelial, and mesenchymal trajectories.

2022-12-21 | GSE164336 | GEO

Cardiac organoids reveal mechanisms of human cardiogenesis

Project description:Self-organisation and coordinated morphogenesis of multiple cardiac lineages is essential for the development and function of the heart1-3. However, the absence of a human in vitro model that mimics the basic lineage architecture of the heart hinders research into developmental mechanisms and congenital defects4. Here, we describe the establishment of a reliable, lineage-controlled and high-throughput cardiac organoid platform. We show that cardiac mesoderm derived from human pluripotent stem cells robustly self-organises and differentiates into cardiomyocytes forming a cavity. Co-differentiation of cardiomyocytes and endothelial cells from cardiac mesoderm within these structures is required to form a separate endothelial layer. As in vivo, the epicardium engulfs these cardiac organoids, migrates into the cardiomyocyte layer and differentiates. We use this model to demonstrate that cardiac cavity formation is controlled by a mesodermal WNT-BMP signalling axis. Disruption of one of the key BMP targets in cardiac mesoderm, the transcription factor HAND1, interferes with cavity formation, which is consistent with its role in early heart tube and left chamber development5. Thus, the cardiac organoid platform represents a powerful resource for the quantitative and mechanistic analysis of early human cardiogenesis and defects that are otherwise inaccessible. Beyond understanding congenital heart disease, cardiac organoids provide a foundation for future translational research into human cardiac disorders.

2021-05-18 | PXD018306 | Pride

Transcriptional silencers in Drosophila serve a dual role as transcriptional enhancers in alternate cellular contexts [HiChIP]

Project description:Silencers active in the Drosophila embryonic mesoderm were identified by reporter assays in dissociated embryonic cells. We find that, despite the presence of ChIP peaks for known transcriptional corepressors and marks of repressed chromatin, the only significantly enriched source of mesodermal silencers is non-mesodermal enhancers. We present evidence that a subset of silencers acts by looping to target promoters.

2019-09-25 | GSE137949 | GEO

Epigenetic and transcriptional analysis of mesoderm progenitor cells identifies HOPX as a novel regulator of hemogenic endothelium

Project description:We analyzed chromatin dynamics and transcriptional activity of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) and KDR+/CD34+ endothelial cells generated from cardiogenic or hemogenic mesoderm. Using an unbiased algorithm to hierarchically rank genes modulated at the level of chromatin and transcription, we identified novel candidate regulators of mesodermal lineage determination. HOPX, a non-DNA binding homeodomain protein, was identified as a candidate regulator of blood-forming endothelial cells. We used HOPX reporter and knockout hESCs, as well as hopx loss of function studies in zebrafish, to show the requirement of HOPX in vivo and in vitro in hemato-endothelial lineage specification. Loss of HOPX does not impact endothelial fate specification but markedly reduces primitive hematopoiesis acting at least in part through suppression of Wnt/β-catenin signaling. Single cell RNA-seq data during mouse hematopoietic development in vivo confirm a role for HOPX in hematopoietic fate. Taken together, we show that HOPX is a novel regulator of hemato-endothelial fate specification in vitro and in vivo that functionally regulates Wnt signaling to modulate primitive hematopoiesis.

2017-08-16 | GSE97080 | GEO

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