Low Intracellular Calcium is an Essential Feature of Hematopoietic Stem Cells
78 Pages Posted: 16 Aug 2018 Last revised: 27 Aug 2018 Publication Status: Review CompleteMore...
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. HSC maintenance in low calcium conditions was mediated by inhibition of calpain proteases. Consistent with the fact that TET enzymes are targets of calpains, low calcium increased TET protein expression and 5-hydroxymethyl cytosine deposition and maintained TET2-asssociated single cell gene signature. Deletion of the TET homologue required for normal HSC function and identity, TET2, rendered HSC impervious to the effect low calcium conditions. These observations reveal a physiological feature of HSCs than can be harnessed to improve their maintenance in vitro.
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