Reduced lymphomyeloid repopulating activity from adult bone marrow and fetal liver of mice lacking expression of STAT5

Author:

Bunting Kevin D.1,Bradley Heath L.1,Hawley Teresa S.1,Moriggl Richard1,Sorrentino Brian P.1,Ihle James N.1

Affiliation:

1. From the Hematopoiesis Department, American Red Cross Holland Laboratory, Rockville, MD; the Research Institute of Molecular Pathology, Vienna, Austria; the Division of Experimental Hematology and the Biochemistry Department, St Jude Children's Research Hospital, Memphis, TN; and the Howard Hughes Medical Institute, Chevy Chase, MD.

Abstract

AbstractSignal transducers and activators of transcription (STATs) are intracellular mediators of cytokine receptor signals. Because many early-acting growth factors have been implicated in STAT5 activation, this study sought to investigate whether STAT5 may be a transcriptional regulator of hematopoietic stem cell (HSC) long-term repopulating activity. To test this possibility, bone marrow (BM) and fetal liver (FL) cells from mice containing homozygous deletions of both STAT5a and STAT5b genes (STAT5ab−/−) were characterized for hematopoietic repopulating activities. BM and FL grafts were capable of repopulating lymphoid and myeloid lineages of lethally irradiated primary and secondary hosts, with defects observed primarily in T-lymphocyte engraftment. Because only a fraction of normal HSC function is required to reconstitute hematopoiesis, competitive repopulation assays of adult BM or FL cells were used against wild type adult BM or FL cells to quantitate stem cell function. In these analyses, average 25-, 28-, 45-, and 68-fold decreases in normal repopulating activity were evident in granulocyte (Gr-1+), macrophage (Mac-1+), erythroid progenitor (Ter119+), and B-lymphocyte (B220+) populations, respectively, with T lymphocytes (CD4+) always undetectable from the STAT5ab−/− graft. Consistent with previous reports of divergence between stem cell phenotype and function in cases of perturbed hematopoiesis, the absolute number of cells within Sca-1+c-kit+lin− or lin− Hoechst 33342 side population fractions was not significantly different between wild type and STAT5ab−/−BM or FL cells. These results demonstrate that a significant proportion of the growth factor signals required for multilineage reconstitution potential of HSCs is STAT5 dependent.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3