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Harnessing Hematopoietic Stem Cell Low Intracellular Calcium Improves Their Maintenance In Vitro.

Cell Stem Cell. 2019; 
Luchsinger LL, Strikoudis A, Danzl NM, Bush EC, Finlayson MO, Satwani P, Sykes M, Yazawa M, Snoeck HW.
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摘要

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 revea... More

关键词

TET enzymes; calcium; calpains; culture; hematopoiesis; hematopoietic stem cells