Novel differential calcium regulation of hematopoietic stem and progenitor cells under physiological low oxygen conditions

Novel differential calcium regulation of hematopoietic stem and progenitor cells under physiological low oxygen conditions

Paige Dausinas Ni

Melissa Hartman

Jacob Slack

Christopher Basile

Sheng Liu

Jun Wan

Heather A O'Leary

Journal of Cell Physiology

2023 Apr 13

Low oxygen bone marrow (BM) niches (~1%-4% low O₂ ) provide critical signals for hematopoietic stem/progenitor cells (HSC/HSPCs). Our presented data are the first to investigate live, sorted HSC/HSPCs in their native low O₂ conditions. Transcriptional and proteomic analysis uncovered differential Ca²⁺ regulation that correlated with overlapping phenotypic populations consisting of robust increases of cytosolic and mitochondrial Ca²⁺ , ABC transporter (ABCG2) expression and sodium/hydrogen exchanger (NHE1) expression in live, HSC/HSPCs remaining in constant low O_2. We identified a novel Ca²⁺ high population in HSPCs predominantly detected in low O₂ that displayed enhanced frequency of phenotypic LSK/LSKCD150 in low O₂ replating assays compared to Ca²⁺ low populations. Inhibition of the Ca²⁺ regulator NHE1 (Cariporide) resulted in attenuation of both the low O₂ induced Ca²⁺ high population and subsequent enhanced maintenance of phenotypic LSK and LSKCD150 during low O₂ replating. These data reveal multiple levels of differential Ca²⁺ regulation in low O₂ resulting in phenotypic, signaling, and functional consequences in HSC/HSPCs.

doi: 10.1002/jcp.30942. Online ahead of print.

English