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

被引：0
|
作者：
Ni, Paige Dausinas [1 ,2 ]
Hartman, Melissa [1 ,2 ]
Slack, Jacob [1 ,2 ]
Basile, Christopher [1 ,2 ]
Liu, Sheng [3 ]
Wan, Jun [3 ]
O'Leary, Heather A. [1 ,2 ,4 ,5 ]
机构：
[1] Indiana Univ Sch Med, Dept Anat Cell Biol & Physiol, Indianapolis, IN USA
[2] Indiana Univ Sch Med, Dept Med, Indianapolis, IN USA
[3] Indiana Univ Sch Med, Ctr Computat Biol & Bioinformat, Dept Med & Mol Genet, Indianapolis, IN USA
[4] Northeast Ohio Med Univ, Dept Integrat Med Sci, Rootstown, OH USA
[5] Northeast Ohio Med Univ, Dept Integrat Med Sci, Rootstown, OH 44272 USA
来源：
JOURNAL OF CELLULAR PHYSIOLOGY | 2023年 / 238卷 / 07期
关键词：
ABC transporter; Ca2+; HSC; HSPC; low oxygen tension; NHE1; BONE-MARROW; INTRACELLULAR PH; GENE-EXPRESSION; ABC TRANSPORTERS; HYPOXIA; MAINTENANCE; EXPANSION; DISTINCT; SURVIVAL; PROFILE;
D O I：
10.1002/jcp.30942
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Low oxygen bone marrow (BM) niches (similar to 1%-4% low O-2) 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 O-2 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 O-2 that displayed enhanced frequency of phenotypic LSK/LSKCD150 in low O-2 replating assays compared to Ca2+ low populations. Inhibition of the Ca2+ regulator NHE1 (Cariporide) resulted in attenuation of both the low O-2 induced Ca2+ high population and subsequent enhanced maintenance of phenotypic LSK and LSKCD150 during low O-2 replating. These data reveal multiple levels of differential Ca2+ regulation in low O-2 resulting in phenotypic, signaling, and functional consequences in HSC/HSPCs.
引用
收藏
页码：1492 / 1506
页数：15
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