Title
Brief report: serpin Spi2A as a novel modulator of hematopoietic progenitor cell formation.
Document Type
Article
Publication Date
9-1-2014
Institution/Department
MMCRI
Journal Title
Stem cells (Dayton, Ohio)
MeSH Headings
Animals, Hematopoietic Stem Cells, Mice, Serpins
ISSN
1549-4918
Abstract
Prime regulation over hematopoietic progenitor cell (HPC) production is exerted by hematopoietins (HPs) and their Janus kinase-coupled receptors (HP-Rs). For HP/HP-R studies, one central challenge in determining specific effects involves the delineation of nonredundant signal transduction factors and their lineage restricted actions. Via loss-of-function studies, we define roles for an HP-regulated Serpina3g/Spi2A intracellular serpin during granulomyelocytic, B-cell, and hematopoietic stem cell (HSC) formation. In granulomyelocytic progenitors, granulocyte macrophage colony stimulating factor (GMCSF) strongly induced Serpina3g expression with Stat5 dependency. Spi2A-knockout (KO) led to 20-fold decreased CFU-GM formation, limited GMCSF-dependent granulocyte formation, and compromised neutrophil survival upon tumor necrosis factor alpha (TNF-α) exposure. In B-cell progenitors, Serpina3g was an interleukin-7 (IL7) target. Spi2A-KO elevated CFU-preB greater than sixfold and altered B-cell formation in competitive bone marrow transplant (BMT), and CpG challenge experiments. In HSCs, Serpina3g/Spi2A expression was also elevated. Spi2A-KO compromised LT-HSC proliferation (as well as lineage(neg) Sca1(pos) Kit(pos) (LSK) cell lysosomal integrity), and skewed LSK recovery post 5-FU. Spi2A therefore functions to modulate HP-regulated immune cell and HSC formation post-5-FU challenge.
First Page
2550
Recommended Citation
Li, Lei; Byrne, Susan M; Rainville, Nicole; Su, Su; Jachimowicz, Edward; Aucher, Anne; Davis, Daniel M; Ashton-Rickardt, Philip G; and Wojchowski, Don M, "Brief report: serpin Spi2A as a novel modulator of hematopoietic progenitor cell formation." (2014). Maine Medical Center. 221.
https://knowledgeconnection.mainehealth.org/mmc/221
Last Page
2556