Mutation of STAT1/3 binding sites in gp130FXXQ knock-in mice does not alter hematopoietic stem cell repopulation or self-renewal potential

• Type of Material: Article
• Authors: Zhengqi Wang, Emory University; Zizhen Kang, Cleveland Clinic; Yi Zhang, Institute of Basic Medical Sciences; William Tse, West Virginia University Health Science Center; Kevin Bunting, Emory University
• Language: English
• Date: 2012-06-30
• Publisher: e-Century Publishing
• Publication Version: Final Published Version
• Copyright Statement: © 2012
• License: Creative Commons Attribution-Noncommercial 3.0 Unported
• Title of Journal or Parent Work: American Journal of Stem Cells
• ISSN: 2160-4150
• Volume: 1
• Issue: 2
• Start Page: 146
• End Page: 153
• Grant/Funding Information: This work was supported by NIH R01DK059380 (K.D. Bunting), the Flow Cytometry and Radiation Resources Core Facilities of the Case Comprehensive Cancer Center (P30CA43703), and the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta Flow Cytometry Core facility.
• Keywords: Signal transducer and activator of transcription; hematopoietic stem cell; cytokine signaling; fetal liver
• Research Categories: Health Sciences, Immunology; Health Sciences, Oncology

Abstract

Interleukin (IL)-6 family cytokine signaling through gp130 and signal transducer and activator of transcription (STAT) activation is believed important for early hematopoiesis. To determine whether gp130/STAT1/3 physical interaction is required, we compared hematopoietic repopulating activities of embryonic day (E)14.5 fetal liver cells from gp130FXXQ/FXXQ knock-in mice, which have four mutated STAT1/3 binding sites. In hematopoietic cells, failure to tyrosine phosphorylate STAT3 by gp130 did not cause any significant effects on myeloid progenitor colony forming units (CFU) in vitro and or on competitive multilineage hematopoietic reconstitution. Serial transplantation of fetal liver (FL) cells was unaffected throughout primary, secondary, and tertiary transplants indicating normal self-renewal capacity. Even gp130FXXQ/FXXQ on the background of STAT5 deficiency, with known hematopoietic stem cell (HSC) repopulating dysfunction, did not further impair HSCs beyond that of STAT5 alone. Overall, the defective gp130-mediated STAT1/3 signaling is surprisingly dispensable for HSC function. However, since these mice lack both STAT1/3 binding sites there are several possible explanations for this result and these are discussed.