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

Harnessing Hematopoietic Stem Cell Low Intracellular Calcium Improves Their Maintenance In Vitro.
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DOI:
10.1016/j.stem.2019.05.002
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发表时间:
2019-08-01
期刊:
影响因子:
23.9
通讯作者:
Snoeck HW
Snoeck HW
中科院分区:
医学1区
文献类型:
--
作者:
Luchsinger LL;Strikoudis A;Danzl NM;Bush EC;Finlayson MO;Satwani P;Sykes M;Yazawa M;Snoeck HW

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The specific cellular physiology of hematopoietic stem cells (HSCs) is underexplored and their maintenance in vitro remains challenging. We discovered that culture of HSC 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 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 than can be harnessed to improve their maintenance in vitro.
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