Signals controlling maintenance and differentiation of embryonic gastric epithelial progenitors
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ABSTRACT:
PROVIDER: PRJNA573843 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10172300.fastq.gz | Fastqsanger.gz | |||
| SRR10172400.fastq.gz | Fastqsanger.gz | |||
| SRR10172500.fastq.gz | Fastqsanger.gz | |||
| SRR10172600.fastq.gz | Fastqsanger.gz | |||
| SRR10172700.fastq.gz | Fastqsanger.gz |
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Project description:A dozen of cells expressing various marker genes was defined as adult gastric epithelial stem cells. Do these cells represent different cell types or they are just the same cell with cycling expression of different marker genes? The origin of the adult stem cells could answer this question. Yet, the identity of the embryonic gastric progenitors was not known. We performed single cell RNA-sequencing to characterize cellular composition of the embryonic stomach at the time of initiation of cytodifferentiation. Our analysis of the scRNA-seq data led to identification of two different embryonic gastric epithelial progenitors. Further, we have defined signals that control their maintenance and differentiation along four main lineages, such as mucous pit, zymogenic, parietal and endocrine cells.
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Project description:Hematopoietic stem cells (HSCs) primarily reside in the bone marrow where signals generated by stromal cells regulate their self-renewal, proliferation, and trafficking. Endosteal osteoblasts and perivascular stromal cells including endothelial cells3, CXCL12-abundant reticular (CAR) cells, leptin-receptor positive stromal cells, and nestin-GFP positive mesenchymal progenitors have all been implicated in HSC maintenance. However, it is unclear if specific hematopoietic progenitor cell (HPC) subsets reside in distinct niches defined by the surrounding stromal cells and the regulatory molecules they produce. CXCL12 (stromal-derived factor-1, SDF-1) regulates both HSCs and lymphoid progenitors and is expressed by all of these stromal cell populations. Here, we selectively deleted Cxcl12 from candidate niche stromal cell populations and characterized the effect on HPCs. Deletion of Cxcl12 from mineralizing osteoblasts has no effect on HSCs or lymphoid progenitors. Deletion of Cxcl12 from osterix-expressing stromal cells, which includes CAR cells and osteoblasts, results in constitutive HPC mobilization and a loss of B lymphoid progenitors, but HSC function is normal. Cxcl12 deletion in endothelial cells results in a modest loss of long-term repopulating activity. Strikingly, deletion of Cxcl12 in nestin-negative mesenchymal progenitors using Prx1-Cre is associated with a marked loss of HSCs, long-term repopulating activity, HSC quiescence, and common lymphoid progenitors. These data suggest that osterix-expressing stromal cells comprise a distinct niche that supports B lymphoid progenitors and retains HPC in the bone marrow, while expression of CXCL12 from stromal cells in the perivascular region, including endothelial cells and mesenchymal progenitors, support HSCs.
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