Isolation of long-term hematopoietic stem cell (HSC) is possible by utilizing flow cytometry with multiple cell surface markers. However, those cell surface phenotypes do not represent functional HSCs after culture. Here we show that cultured HSCs express mast cell-related genes including . After culture, phenotypic HSCs were divided into CD244 and CD244 subpopulations, and only CD244 cells that have low mast cell gene expression and maintain HSC-related genes sustain reconstitution potential. The result was same when HSCs were cultured in an efficient expansion medium containing polyvinyl alcohol. Chemically induced endoplasmic reticulum (ER) stress signal increased the CD244 subpopulation, whereas ER stress suppression using a molecular chaperone, TUDCA, decreased CD244 population, which was correlated to improved reconstitution output. These data suggest CD244 is a potent marker to exclude non-functional HSCs after culture thereby useful to elucidate mechanism of functional decline of HSCs during treatment.
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| http://dx.doi.org/10.1016/j.isci.2021.103603 | DOI Listing |
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