Open AccessNfix Promotes Survival of Immature Hematopoietic Cells via Regulation of c‐Mpl
Author(s) -
Hall Trent,
Walker Megan,
Ganuza Miguel,
Holmfeldt Per,
Bordas Marie,
Kang Guolian,
Bi Wenjian,
Palmer Lance E.,
Finkelstein David,
McKinneyFreeman Shan
Publication year - 2018
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2800
Subject(s) - biology , haematopoiesis , progenitor cell , microbiology and biotechnology , ex vivo , stem cell , ectopic expression , thrombopoietin , cancer research , immunology , in vivo , cell culture , genetics
Hematopoietic stem and progenitor cells (HSPCs) are necessary for life‐long blood production and replenishment of the hematopoietic system during stress. We recently reported that nuclear factor I/X ( Nfix) promotes HSPC survival post‐transplant. Here, we report that ectopic expression of Nfix in primary mouse HSPCs extends their ex vivo culture from about 20 to 40 days. HSPCs overexpressing Nfix display hypersensitivity to supportive cytokines and reduced apoptosis when subjected to cytokine deprivation relative to controls. Ectopic Nfix resulted in elevated levels of c‐Mpl transcripts and cell surface protein on primary murine HSPCs as well as increased phosphorylation of STAT5, which is known to be activated down‐stream of c‐MPL. Blocking c‐MPL signaling by removal of thrombopoietin or addition of a c‐MPL neutralizing antibody negated the antiapoptotic effect of Nfix overexpression on cultured HSPCs. Furthermore, NFIX was capable of binding to and transcriptionally activating a proximal c‐Mpl promoter fragment. In sum, these data suggest that NFIX‐mediated upregulation of c‐Mpl transcription can protect primitive hematopoietic cells from stress ex vivo. S tem C ells 2018;36:943–950