Tracing the first hematopoietic stem cell generation in human embryo by single-cell RNA sequencing
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ABSTRACT:
PROVIDER: PRJNA557711 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9875920_1.fastq.gz | Fastqsanger.gz | |||
| SRR9875920_2.fastq.gz | Fastqsanger.gz | |||
| SRR9875930_1.fastq.gz | Fastqsanger.gz | |||
| SRR9875930_2.fastq.gz | Fastqsanger.gz | |||
| SRR9875921_1.fastq.gz | Fastqsanger.gz |
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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
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 the technical limitations and the 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 (HECs) were captured at Carnegie stage (CS) 12-14 in an unbiased way, showing an unambiguous feature of arterial endothelial cells (ECs) with the up-regulation of RUNX1, MYB and ANGPT1. Importantly, subcategorizing CD34+CD45- ECs into a CD44+ population strikingly enriched HECs by over 10-fold. We further mapped the developmental path from arterial ECs via HSC-primed HECs 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 HEC 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 HECs. The cellular and molecular programs that underlie the generation of the first HSCs from HECs in human embryos, together with the ability to distinguish the HSC-primed HECs from others, will shed light on the strategies for the production of clinically useful HSCs from pluripotent stem cells.
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Project description:In vivo lineage tracing holds great potential to reveal fundamental principles of tissue development and homeostasis. However, lineage tracing in humans relies on DNA mutations that are extremely rare. In mice, the improved genetic labeling approach has low resolution over cell division histories. Here, we demonstrated for the first time that frequent epimutations on DNA methylation can be exploited to infer lineage histories in normal cells, enabled by our newly developed computational method MethyTree. Using both in-house and public sparse single-cell DNA methylation datasets with known lineage labels, MethyTree reconstructed lineage histories at high resolution and accuracy across different cell types, stages, and species. Applying MethyTree, we identified the first fate decision in human embryo development and pinpointed in total ~230 clones of hematopoietic stem cells in mice. Our study opens the door for high-resolution, noninvasive lineage tracing in mice, humans and beyond.
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Project description:In vivo lineage tracing holds great potential to reveal fundamental principles of tissue development and homeostasis. However, lineage tracing in humans relies on DNA mutations that are extremely rare. In mice, the improved genetic labeling approach has low resolution over cell division histories. Here, we demonstrated for the first time that frequent epimutations on DNA methylation can be exploited to infer lineage histories in normal cells, enabled by our newly developed computational method MethyTree. Using both in-house and public sparse single-cell DNA methylation datasets with known lineage labels, MethyTree reconstructed lineage histories at high resolution and accuracy across different cell types, stages, and species. Applying MethyTree, we identified the first fate decision in human embryo development and pinpointed in total ~230 clones of hematopoietic stem cells in mice. Our study opens the door for high-resolution, noninvasive lineage tracing in mice, humans and beyond.
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Project description:Whereas hundreds of endothelial cells in the aorta-gonad-mesonephros (AGM) region transdifferentiate to hematopoietic cells, only 1-2 of these cells take on hematopoietic stem cell (HSC) identity at a single time point. Gata2 is one of a few transcription factors essential for HSC generation and function. In contrast to cell surface marker-based HSC enrichment approaches, enrichment based on Gata2 expression is directly linked to the internal regulatory network critical for HSC identity. Here we use index sorting of highly enriched Gata2-expressing intra-aortic hematopoietic cluster (IAHC) cells, iterative single cell transcriptomics and functional analyses to examine the relationship between HSC identity and expression of pivotal factors. Functional HSCs are enriched in Gata2 medium-expressing IAHC cells, which can be further subdivided based on Gata2, cKit and CD27 expression, where each subpopulation is not only associated with a specific molecular profile, but also distinct functionality in both in vitro and in vivo stem/progenitor assays. Immunohistochemical analysis localizes the first putative functional HSCs in vivo to small clusters in the AGM region, thus integrating molecular, functional and spatial information about the first cells in a mammalian embryo that acquire full HSC identity.
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