Am J Stem Cell 2012;1(2):146-153

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

Zhengqi Wang, Zizhen Kang, Yi Zhang, William Tse, Kevin D Bunting

Aflac Cancer Center of Children’s Healthcare of Atlanta and Emory University Department of Pediatrics, Atlanta, GA, USA; Department of
Immunology, Cleveland Clinic, Cleveland, OH, USA; Department of Biology, Institute of Basic Medical Sciences, Beijing, China; Mary
Babb Randolph Cancer Center, Department of Medicine, West Virginia University Health Science Center, Morgantown, WV, USA.

Received April 30, 2012; accepted May 15, 2012; Epub May 18, 2012; Published June 30, 2012

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. (AJSC1204002).

Keywords: Signal transducer and activator of transcription, hematopoietic stem cell, cytokine signaling, fetal liver

Address all correspondence to:
Dr. Kevin D Bunting
Division of Hem/Onc/BMT
Aflac Cancer Center and Blood Disorders Service
2015 Uppergate Dr. NE, ECC #444, Atlanta, GA 30322, USA.
Tel: 404-778-4039; Fax: 404-727-4455

Dr. William Tse
Mary Babb Randolph Cancer Center
Department of Medicine, 2nd Fl Cancer Center
P.O. Box 9162, Morgantown, WV 26506, USA.
Tel: 304-293-4980; Fax: 304-293-2519
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