Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Embryonic Endothelial Evolution towards First Hematopoietic Stem Cells Revealed by Single-Cell Transcriptomic and Functional Analyses

ABSTRACT: Hematopoietic stem cells (HSCs) in adults are believed to be born from hemogenic endothelial cells (HECs) in mid-gestational mouse embryos. Due to rare and transient nature, the HSC-competent ECs have never been stringently identified and accurately captured, let alone their genuine vasculature precursors. Here, we firstly used high-precision single-cell transcriptomics to unbiasedly examine relevant EC populations at continuous developmental stages and transcriptomically identified putative HSC-primed HECs. Combining computational prediction and in vivo functional validation, we precisely captured HSC-competent HECs by newly constructed Neurl3-EGFP reporter mouse model, and realized enrichment further by surface marker combination. Surprisingly, endothelial-hematopoietic bi-potential was rarely but reliably witnessed in culture of single HECs. Noteworthy, primitive vascular ECs experienced two-step fate choices to become HSC-primed HECs, resolving several previously observed contradictions. Taken together, comprehensive understanding of endothelial evolutions and molecular programs underlying HSC-primed HEC specification in vivo will facilitate future investigations directing HSC production in vitro.

ORGANISM(S): Mus musculus

PROVIDER: GSE139389 | GEO | 2020/03/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Tracing the first hematopoietic stem cell generation in human embryo by single-cell RNA sequencing

Project description:Tracing the emergence of the first hematopoietic stem cells (HSCs) in human embryos, particularly the scarce and transient precursors thereof, is so far challenging, largely due to technical limitations and material rarity. Here, using single-cell RNA sequencing, we constructed the first genome-scale gene expression landscape covering the entire course of endothelial-to-HSC transition during human embryogenesis. The transcriptomically defined HSC-primed hemogenic endothelial cells (ECs) were captured at Carnegie stage 12-14 in an unbiased way, showing an unambiguous arterial EC feature with the up-regulation of RUNX1, MYB and ANGPT1. Importantly, subcategorizing CD34+CD45- ECs into CD44+ population strikingly enriched hemogenic ECs by over 10-fold. We further mapped the developmental path from arterial ECs via HSC-primed hemogenic ECs to hematopoietic stem progenitor cells, and revealed a distinct expression pattern of genes that were transiently over-represented upon the hemogenic fate choice of arterial ECs, including EMCN, PROCR and RUNX1T1. We also uncovered another temporally and molecularly distinct intra-embryonic hemogenic EC population, which was detected mainly at earlier CS 10 and lacked the arterial feature. Finally, we revealed the cellular components of the putative aortic niche and potential cellular interactions acting on the HSC-primed hemogenic ECs. The cellular and molecular programs and interactions that underlie the generation of the first HSCs from hemogenic ECs in human embryos, together with distinguishing HSC-primed hemogenic ECs from others, will shed light on the strategies for the production of clinically useful HSCs from pluripotent stem cells.

2019-09-09 | GSE135202 | GEO

Spatiotemporal and functional heterogeneity of the hematopoietic stem cell-competent hemogenic endothelial cells in mouse embryos

Project description:Hematopoietic stem cells (HSCs) are derived from hemogenic endothelial cells (HECs) during embryogenesis. The HSC-primed HECs are peak at embryonic day (E) 10 and have been efficiently captured by the marker combination CD41-CD43-CD45-CD31+CD201+Kit+CD44+ (PK44) in the aorta-gonad-mesonephros (AGM) region of mouse embryos most recently. In the present study, we investigated the spatiotemporal and functional heterogeneity of PK44 cells around the time of emergence of HSCs. First, PK44 cells in E10 AGM region could be further divided into three molecularly different populations showing endothelial- or hematopoietic-biased characteristics. Specifically, with the combination of Kit, the expression of CD93 or CD146 could divide PK44 cells into endothelial- and hematopoietic-feature biased populations, which was further functionally validated at single cell level. Next, PK44 population could also be detected in the yolk sac, showing a developmental dynamics and functional diversification similar to those in the AGM region. Importantly, PK44 cells in the yolk sac demonstrated an unambiguous multi-lineage reconstitution capacity after in vitro incubation. Regardless of the functional similarity, PK44 cells in the yolk sac displayed transcriptional features different to those in the AGM region. Taken together, our work delineated the spatiotemporal characteristics of HECs represented by PK44, and revealed a previously unknown HSC competence of HECs in the yolk sac. These findings provided a fundamental basis for in-depth studying the different origins and molecular programs of HSC generation in the future.

2021-08-20 | GSE173833 | GEO

Adult-repopulating lymphoid potential is not confined to the arterial endothelial cells in yolk sac

Project description:During embryogenesis, hematopoietic stem progenitor cells (HSPCs) are believed to be derived from hemogenic endothelial cells (HECs). Moreover, arterial feature is proposed to be a prerequisite for the HECs to generate HSPCs with lymphoid potential. Whereas the molecular basis of the hematopoietic stem cell-competent HECs has been delicately elucidated within the embryo proper, the functional and molecular heterogeneity of HECs in the extra-embryonic yolk sac (YS) remains largely unresolved. In this study, we firstly identified six molecularly different endothelial populations in the mid-gestational YS through integrated analysis of several single-cell RNA sequencing (scRNA-seq) datasets, and validated the arterial vasculature distribution of Gja5+ ECs by using a Gja5-EGFP reporter mouse model. We further explored the hemogenic potential of different EC populations based on their Gja5- EGFP and CD44 expression. The lineage differentiation potentials of ECs were spatiotemporally different and the B lymphoid potential was detected in the YS ECs as early as embryonic day (E) 8.5 regardless of their arterial feature. Unexpectedly, capacity of generating hematopoietic progenitors with in vivo lymphoid potential was found in non-arterial in addition to arterial YS ECs at E10.0-E10.5. Importantly, the distinct identities of E10.0-E10.5 ECs with a hemogenic potential between those from YS and from intra-embryonic caudal region were revealed by further scRNA-seq analysis. Taken together, these findings extend our knowledge about the hemogenic potential of ECs from anatomically and molecularly different vascular beds, providing a theoretical basis for better understanding the sources of HSPCs during mammalian development.

2021-07-12 | GSE167588 | GEO

Single cell RNA-sequencing of Tumor-Associated High Endothelial Cells (TA-HECs) and comparison to their counterparts in homeostatic and inflamed mouse lymph nodes

Project description:High endothelial venules (HEVs) are specialized postcapillary venules that mediate lymphocyte trafficking from the blood into lymph nodes. HEV-like blood vessels are found in solid tumors in association with CD8+ T cell infiltration.This study uses single cell RNA-sequencing using the Fluidigm C1 system as a method to evaluate the transcriptome in lymph node and tumor-associated HEV endothelial cells (LN-HECs and TA-HECs). We isolated MECA-79+ TA-HECs and CD31+MECA-79- tumor-associated endothelial cells (TA-ECs) by cell sorting and we compared their transcriptome to those of their counterparts in homeostatic (LN-HECs and LN-ECs) or inflamed (iLN-HECs) lymph nodes. TA-HECs express high levels of endothelial cell markers Cdh5 and Pecam1 (CD31), post-capillary venule marker Ackr1 (DARC) and venous transcription factor Nr2f2, indicating that they correspond to post-capillary venule endothelium, like their lymph node counterparts. The genes encoding HEV sialomucins decorated by the sulfated MECA-79 epitope (CD34 and Emcn, endomucin) and the core 1 branching enzyme B3gnt3 that is essential for its biosynthesis, are equally expressed in all HEC populations, whereas sulfotransferases Chst2 and Chst4 are expressed at lower levels in TA-HECs. Although TA-HECs are molecularly distinct from lymph node HECs, they share several important characteristics with iLN-HECs, including the upregulation of endothelial selectins (Selp, Sele) and inflammatory chemokines CXCL9 and CXCL10, the ligands for chemokine receptor CXCR3 on effector T cells. Finally, endothelial cell adhesion molecules ICAM1, ICAM2 and VCAM1 that are important for lymphocyte sticking to HEVs, are expressed at similar levels in all HECs. Together, these findings indicated that MECA-79+ TA-HECs, similar to HECs in immune-stimulated lymph nodes, exhibit an inflamed phenotype characterized by co-expression of MECA-79+ antigens with endothelial selectins and inflammatory chemokines.

2021-12-14 | GSE154898 | GEO

The para-aortic splanchnopleure (P-Sp) of mouse embryos

Project description:The hematopoietic stem cells (HSCs) arise from hemogenic endothelial cells (HECs) in the para-aortic splanchnopleure (P-Sp)/aorta-gonad-mesonephros (AGM) region of mouse embryos. HECs differentiate into HSC precursors and blood progenitors and form intra-aortic hematopoietic clusters (IAHCs) in the aorta. To identify HECs in distinction from endothelial cells, we performed single-cell RNA-seq analysis of cells isolated from the dorsal aorta and its surrounding tissues at E9.5. We found the population of HECs in the arterial endothelial cell cluster. Therefore, our data might elucidate the mechanism of HEC development.

2024-10-16 | GSE271523 | GEO

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

Runx1+ vascular smooth muscle cells are essential for hematopoietic stem and progenitor cell development in vivo

Project description:We sequenced 4 sorted cell populations: ECs, HECs, Runx1+ IAHCs and Runx1- IAHCs.

2023-11-27 | GSE229850 | GEO

Pre-configuring chromatin architecture with histone modifications guide hematopoietic stem cell formation in mouse embryos [ChIP-seq]

Project description:We performed multi-omics exploration of early aorta endothelial cells (AECs), hemogenic endothelial cells (HECs), pre-HSCs and long-term HSCs (LT-HSCs) along definitive HSC emergence in mouse embryos. Globally, we find that most hematopoiesis related enhancers were already pre-activated at the beginning, followed by strengthened looping structure of enhancers and promoters. After the stronger interactions forming, enhancers can be further activated to promote hematopoiesis gene expressions. Specifically, the important hematopoietic transcription factor (TF) RUNX1 can mediate enhancer-promoter interactions, which starts from a subset of early AECs, prior to appearance of HECs. Thus, the stepwise and asynchrony cooperation of multi-omics and TFs in definitive hematopoiesis has been revealed holistically in vivo. It may also reflect general epigenetic regulation models of developmental processes.

2021-12-12 | GSE161327 | GEO

Pre-configuring chromatin architecture with histone modifications guide hematopoietic stem cell formation in mouse embryos [Hi-C]

2021-12-12 | GSE161326 | GEO

The Fc receptor CD32 identifies primed human hemogenic endothelial cells [RNA-seq]

Project description:During embryonic development, blood cells emerge from a subset of specialized endothelial cells, named hemogenic endothelial cells (HECs), via a process known as endothelial-to-hematopoietic transition (EHT). A thorough characterization of HECs and their EHT is essential to guide the efforts to derive this population from human pluripotent stem cells (hPSCs), a critical step to generate therapeutic blood products in vitro. However, current known markers used to isolate HECs are insufficient as they also enrich for arterial endothelial cells that are associated with HECs. To identify specific human HEC markers, we performed transcriptomic analysis of 28-32-day human embryos, a developmental stage characterized by active EHT. We observed that the expression of FCGR2B, encoding for the Fc receptor CD32 previously associated with other specialized endothelia, is highly enriched in the ACE+CD34+ endothelial cell population that contains HECs. Functional ex vivo analyses confirmed that multilineage hematopoietic potential is highly enriched in CD32+ endothelial cells isolated from the aorta-gonad-mesonephros region and yolk sac of human embryos. In addition, CD32 emerged as selective marker for hPSC-derived HECs across different hematopoietic programs. Remarkably, our analyses showed that CD32 expression identifies HECs that are irreversibly bound to undergo EHT. As such, CD32 expression enriches for cells with hemogenic potential with a higher specificity for hPSC-derived HECs than other known HEC markers. These findings provide a simple method for isolating HECs from human embryos and hPSC cultures, allowing the efficient generation of hematopoietic cells in vitro.

2024-02-09 | GSE223221 | 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