title: Brief report: serpin Spi2A as a novel modulator of hematopoietic progenitor cell formation.
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.
authors: COBRE Center of Excellence in Stem Cell Biology and Regenerative Medicine, Maine Medical Center Research Institute, Scarborough, Maine, USA; Department of Pediatrics, Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors: Lei
authors: L
authors: Li
authors: Susan M
authors: SM
authors: Byrne
authors: Nicole
authors: N
authors: Rainville
authors: Su
authors: S
authors: Su
authors: Edward
authors: E
authors: Jachimowicz
authors: Anne
authors: A
authors: Aucher
authors: Daniel M
authors: DM
authors: Davis
authors: Philip G
authors: PG
authors: Ashton-Rickardt
authors: Don M
authors: DM
authors: Wojchowski
mesh_terms: D000818:Animals; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D015843:Serpins / Q000378:metabolism*
chemical_list: C490400:Serpina3k protein, mouse; D015843:Serpins
keywords: B cells; GMCSF; Granulomyelocytes; HPC; HSC; Hematopoiesis; Neutrophils; Serpins