| Literature DB >> 31178255 |
Larry L Luchsinger1, Alexandros Strikoudis2, Nichole M Danzl3, Erin C Bush4, Michael O Finlayson4, Prakash Satwani5, Megan Sykes6, Masayuki Yazawa7, Hans-Willem Snoeck8.
Abstract
The specific cellular physiology of hematopoietic stem cells (HSCs) is underexplored, and their maintenance in vitro remains challenging. We discovered that culture of HSCs in low calcium increased their maintenance as determined by phenotype, function, and single-cell expression signature. HSCs are endowed with low intracellular calcium conveyed by elevated activity of glycolysis-fueled plasma membrane calcium efflux pumps and a low-bone-marrow interstitial fluid calcium concentration. Low-calcium conditions inhibited calpain proteases, which target ten-eleven translocated (TET) enzymes, of which TET2 was required for the effect of low calcium conditions on HSC maintenance in vitro. These observations reveal a physiological feature of HSCs that can be harnessed to improve their maintenance in vitro.Entities:
Keywords: TET enzymes; calcium; calpains; culture; hematopoiesis; hematopoietic stem cells
Mesh:
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Year: 2019 PMID: 31178255 PMCID: PMC7649753 DOI: 10.1016/j.stem.2019.05.002
Source DB: PubMed Journal: Cell Stem Cell ISSN: 1875-9777 Impact factor: 24.633