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Updated: Jan 23, 2026

Derivation of Hematopoietic Stem Cells from Murine Embryonic Stem Cells
Published on: February 25, 2007
Harnessing Hematopoietic Stem Cell Low Intracellular Calcium Improves Their Maintenance In Vitro
Larry L Luchsinger1, Alexandros Strikoudis2, Nichole M Danzl3
1Columbia Center of Human Development, Columbia University Irving Medical Center, New York, NY 10032, USA; Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA; New York Blood Center, Lindsley F. Kimball Research Institute, New York, NY 10065, USA.
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.
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