Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Depicting human endothelial to hematopoietic transition and the effects of modulating pyruvate catabolism on blood formation

ABSTRACT: Hematopoietic stem cell (HSC) quiescence, maintenance and differentiation are closely linked to changes in metabolism. However, the role of metabolism during the first emergence of HSCs from hemogenic endothelium (HE) is still unknown. In this study, we focus on the implication of energetic metabolic pathways during endothelial to hematopoietic transition (EHT). EHT is accompanied by a metabolic switch, with concomitant increases in glycolysis and oxidative phosphorylation (OXPHOS). Inhibiting glycolysis in HE cells leads to a block in hematopoietic lineage specification. An OXPHOS fuel, glutamine, is essential for HSC emergence and provides distinct intermediates to mediate differentiation towards the two major hematopoietic lineages, GPA+ and CD45+ cells. Strikingly, shifting the fate of pyruvate from glycolysis to the TCA cycle redirects HE specification towards CD45+ cells at the expense of GPA+ cells and vice versa. As such, our findings reveal the plasticity of hematopoietic lineage specification during EHT which can be modulated by metabolism.

ORGANISM(S): Homo sapiens

PROVIDER: GSE141189 | GEO | 2021/11/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Negative regulation of endothelial to haematopoietic transition by Nupr1

Project description:we uncovered that nuclear protein 1 (Nupr1), a transcription regulatory gene preferentially expressed in HECs, was a negative regulator of EHT. Nupr1 deficiency resulted in plentiful emergence of HSC-competent cells in the AGM region, including HECs and HSPCs. Further single-cell transcriptome combined serial functional assay revealed that loss of Nupr1 prominently accelerate EHT process, also promote the specification of HECs and strengthen their subsequent hematopoietic differentiation potential towards HSPC. Interestingly, we found that numerous inflammatory signals were specifically upregulated in Nupr1-/- EHT relevant populations, as elevated inflammatory response signals have been proved to promote EHT and HSPCs generation.

2022-06-10 | GSE205595 | GEO

Expression data from developing hematopoietic stem and progenitor cells

Project description:In the mouse embryo during midgestation, hematopoietic stem cells (HSCs) are generated from aortic endothelium through the transdifferentiation process known as endothelial-to-hematopoietic transition, or EHT. During EHT, flat-shaped hemogenic endothelium transform into round-shaped hematopoietic cells, which subsequently form cell aggregates, called hematopoietic clusters. To understand HSC specification during ontogeny and to search for nascent HSC markers, we performed single-cell microarray analysis of developing HSC populations.

2019-05-01 | GSE113892 | GEO

Whole-transcriptome analysis of endothelial-to-hematopoietic stem cell transition

Project description:Hematopoietic stem cells (HSCs) are generated via a natural transdifferentiation process known as endothelial-to-hematopoietic cell transition (EHT). Due to small numbers of embryonal arterial cells undergoing EHT and the paucity of markers to enrich for hemogenic endothelial cells, the genetic program driving HSC emergence is largely unknown. Here, we use a highly sensitive RNAseq method to examine the whole transcriptome of small numbers of enriched aortic HSCs (CD31+cKit+Ly6aGFP+), hemogenic endothelial cells (CD31+cKit-Ly6aGFP+) and endothelial cells (CD31+cKit-Ly6aGFP-). Comparison of mRNA profiles of endothelial cells, hemogenic endothelial cells, and hematopoietic stem cells generated by deep-sequencing of sorted populations from pool of embryos, in triplicate.

2014-12-14 | E-GEOD-63316 | biostudies-arrayexpress

Overexpression of GATA2 enhances development and maintenance of human embryonic stem cell-derived hematopoietic stem cell-like progenitors

Project description:GATA2 is essential for the endothelial-to-hematopoietic transition (EHT) and generation of hematopoietic stem cells (HSCs). It is poorly understood how GATA2 controls the development of human pluripotent stem cell (hPSC)-derived HSC-like cells. Here, using human embryonic stem cells (hESCs) in which GATA2 overexpression was induced by doxycycline (Dox), we elucidated the dual functions of GATA2 in definitive hematopoiesis before and after the emergence of CD34+CD45+CD90+CD38- HSC-like cells. Specifically, GATA2 promoted expansion of hemogenic precursors via the EHT and then helped to maintain HSC-like cells in a quiescent state by arresting the cell cycle at G0/G1 phase. RNA-sequencing showed that hPSC-derived-HSC-like cells were very similar to human fetal liver-derived HSCs. Our findings will help to elucidate the mechanism that controls the early stages of human definitive hematopoiesis and may help to generate hPSC-derived HSCs.

2019-12-04 | GSE122207 | GEO

Transcriptome analysis of nascent hematopoietic cells II

Project description:During ontogeny, HSCs or progenitors are generated from endothelial cells through the process known as endothelial-to-hematopoietic transition (EHT). After EHT, hematopoietic cells form cell aggregates, called hematopoietic clusters. To obtain mechanistic insight into HSC specification, we compared the gene expression profiles of hematopoietic clusters between caudal half region and yolk sac.

2022-06-22 | GSE168054 | GEO

Whole-transcriptome analysis of endothelial-to-hematopoietic stem cell transition

2014-12-14 | GSE63316 | GEO

Cooperative Transcription Factor Induction Mediates Hemogenic Reprogramming

Project description:During development, hematopoietic stem/progenitor cells (HSPCs) arise from specialized endothelial cells by a process termed endothelial-to-hematopoietic transition (EHT). The genetic program driving human HSPC emergence remains largely unknown. We previously reported that the generation of hemogenic precursor cells from mouse fibroblasts recapitulates developmental hematopoiesis. Here, we demonstrate that human fibroblasts can be reprogrammed into hemogenic cells by the same transcription factors. Induced cells display dynamic EHT transcriptional programs, generate hematopoietic progeny, possess HSPC cell surface phenotype and repopulate immunodeficient mice for three months. Mechanistically, GATA2 and GFI1B interact and co-occupy a cohort of targets. This cooperative binding is reflected by engagement of open enhancers and promoters, initiating silencing of fibroblast genes and activating the hemogenic program. However, GATA2 displays dominant and independent targeting activity during the early phases of reprogramming. These findings shed light on the processes controlling human HSC specification and support generation of reprogrammed HSCs for clinical applications.

2018-12-04 | GSE51025 | GEO

Meis1 establishes the pre-hemogenic endothelial state prior to Runx1 expression [CITE-seq]

Project description:Hematopoietic stem and progenitor cells (HSPCs) originate from an endothelial-to-hematopoietic transition (EHT) during embryogenesis. Characterization of early hemogenic endothelial (HE) cells is required to understand what drives hemogenic specification and to accurately define cells capable of undergoing EHT. Using Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq), we defined the early subpopulation of pre-HE cells based on both surface markers and transcriptomes. We identified the transcription factor Meis1 as an essential regulator of hemogenic cell specification in the embryo prior to Runx1 expression. Meis1 is expressed at the earliest stages of EHT and distinguishes pre-HE cells primed towards the hemogenic trajectory from the arterial endothelial cells that continue towards a vascular fate. Endothelial-specific deletion of Meis1 impaired the formation of functional Runx1-expressing HE which significantly impeded the emergence of pre-HSPC via EHT. Our findings implicate Meis1 in a critical fate-determining step for establishing EHT potential in endothelial cells.

2023-02-22 | GSE197244 | GEO

Meis1 establishes the pre-hemogenic endothelial state prior to Runx1 expression II

2023-02-22 | GSE197400 | GEO

Meis1 establishes the pre-hemogenic endothelial state prior to Runx1 expression

2023-02-02 | GSE196047 | GEO