期刊
ELIFE
卷 11, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.64835
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资金
- National Heart, Lung, and Blood Institute [R01HL142998]
- National Institute of Diabetes and Digestive and Kidney Diseases [K01DK103908]
- American Heart Association [19POST34380221]
- Institute of Neurological Disorders and Stroke [1U24NS120055-01]
- National Institute of General Medical Sciences [R24 GM137200]
- American Society of Hematology
This study tracks single endogenous HSPCs using light microscopy and identifies their exact location and contacts with surrounding cells using scanning electron microscopy. It reveals the interactions and ultrastructure between hematopoietic stem cells and their microenvironment.
The blood system is supported by hematopoietic stem and progenitor cells (HSPCs) found in a specialized microenvironment called the niche. Many different niche cell types support HSPCs, however how they interact and their ultrastructure has been difficult to define. Here, we show that single endogenous HSPCs can be tracked by light microscopy, then identified by serial block-face scanning electron microscopy (SBEM) at multiscale levels. Using the zebrafish larval kidney marrow (KM) niche as a model, we followed single fluorescently labeled HSPCs by light sheet microscopy, then confirmed their exact location in a 3D SBEM dataset. We found a variety of different configurations of HSPCs and surrounding niche cells, suggesting there could be functional heterogeneity in sites of HSPC lodgement. Our approach also allowed us to identify dopamine beta-hydroxylase (dbh) positive ganglion cells as a previously uncharacterized functional cell type in the HSPC niche. By integrating multiple imaging modalities, we could resolve the ultrastructure of single rare cells deep in live tissue and define all contacts between an HSPC and its surrounding niche cell types.
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