puc-header

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 Complete

See all articles by Larry L. Luchsinger

Larry L. Luchsinger

Columbia University - Columbia Center for Human Development (CCHD)

Alexandros Strikoudis

Columbia University - Columbia Center for Human Development (CCHD)

Nichole M. Danzl

Columbia University - Department of Medicine

Prakesh Satwani

Columbia University - Columbia Center for Translational Immunology

Megan Sykes

Columbia University - Department of Medicine

Masayuki Yasawa

Columbia University - Department of Rehabilitation and Regenerative Medicine

Hans-Willem Snoeck

Columbia University - Columbia Center for Human Development (CCHD)

More...

Abstract

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.

Suggested Citation

Luchsinger, Larry L. and Strikoudis, Alexandros and Danzl, Nichole M. and Satwani, Prakesh and Sykes, Megan and Yasawa, Masayuki and Snoeck, Hans-Willem, Low Intracellular Calcium is an Essential Feature of Hematopoietic Stem Cells. Available at SSRN: https://ssrn.com/abstract=3231849 or http://dx.doi.org/10.2139/ssrn.3231849
This version of the paper has not been formally peer reviewed.

Larry L. Luchsinger (Contact Author)

Columbia University - Columbia Center for Human Development (CCHD)

New York, NY 10032
United States

Alexandros Strikoudis

Columbia University - Columbia Center for Human Development (CCHD)

New York, NY 10032
United States

Nichole M. Danzl

Columbia University - Department of Medicine

630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Prakesh Satwani

Columbia University - Columbia Center for Translational Immunology

College of Physicians and Surgeons
630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Megan Sykes

Columbia University - Department of Medicine

630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Masayuki Yasawa

Columbia University - Department of Rehabilitation and Regenerative Medicine

630 West 168th Street, 3rd Floor, Suite 3-470
New York, NY 10032
United States

Hans-Willem Snoeck

Columbia University - Columbia Center for Human Development (CCHD)

New York, NY 10032
United States

Click here to go to Cell.com

Paper statistics

Abstract Views
680
Downloads
32
PlumX Metrics