STAT5 promotes multilineage hematolymphoid development in vivo through effects on early hematopoietic progenitor cells.
The transcription factor signal transducers and activators of transcription 5 (STAT5) is activated by numerous cytokines that orchestrate blood cell development. Multilineage peripheral blood cytopenias were observed in adult mice lacking both isoforms of STAT5 (STAT5A and STAT5B) as well as accelerated rates of apoptosis in the bone marrow. Although the hematopoietic stem cell (HSC) population was preserved in a number of these mice, the post-HSC progenitor populations were diminished and a marked reduction in functional progenitors (spleen colony-forming units) was detected. Competitive bone marrow transplantation studies in vivo revealed a profound impairment of repopulation potential of STAT5-null HSCs, leading to complete lack of contribution to the myeloid, erythroid, and lymphoid lineages. These abnormalities were associated with heightened proliferation activity in the HSC fraction, suggesting the action of homeostatic mechanisms to maintain sufficient levels of diverse blood cell types for viability. Thus, STAT5 normally sustains the robust hematopoietic reserve that contributes to host viability through crucial survival effects on early progenitor cells.
Snow
Jonathan W
JW
Gladstone Institute of Virology and Immunology, Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, CA, USA.
Abraham
Ninan
N
Ma
Melissa C
MC
Abbey
Nancy W
NW
Herndier
Brian
B
Goldsmith
Mark A
MA
D000380:Agranulocytosis; D000818:Animals; D017209:Apoptosis; D001772:Blood Cell Count; D001854:Bone Marrow Cells; D002452:Cell Count; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000502:physiology*; D004912:Erythrocytes / Q000166:cytology; D006098:Granulocytes / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006706:Homeostasis; D008214:Lymphocytes / Q000166:cytology; D008231:Lymphopenia; D051379:Mice; D018345:Mice, Knockout; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; D013154:Spleen / Q000166:cytology; D015534:Trans-Activators / Q000172:deficiency / Q000502:physiology*
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse; D015534:Trans-Activators