Prdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress.
To better understand the mechanisms that regulate stem cell identity and function, we sought to identify genes that are preferentially expressed by stem cells and critical for their function in multiple tissues. Prdm16 is a transcription factor that regulates leukaemogenesis, palatogenesis and brown-fat development, but which was not known to be required for stem cell function. We demonstrate that Prdm16 is preferentially expressed by stem cells throughout the nervous and haematopoietic systems and is required for their maintenance. In the haematopoietic and nervous systems, Prdm16 deficiency led to changes in the levels of reactive oxygen species (ROS), depletion of stem cells, increased cell death and altered cell-cycle distribution. In neural stem/progenitor cells, Prdm16 binds to the Hgf promoter, and Hgf expression declined in the absence of Prdm16. Addition of recombinant HGF to Prdm16-deficient neural stem cells in cell culture reduced the depletion of these cells and partially rescued the increase in ROS levels. Administration of the anti-oxidant, N-acetyl-cysteine, to Prdm16-deficient mice partially rescued defects in neural stem/progenitor cell function and neural development. Prdm16 therefore promotes stem cell maintenance in multiple tissues, partly by modulating oxidative stress.
Chuikov
Sergei
S
Howard Hughes Medical Institute, Department of Internal Medicine, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109-2216, USA.
Levi
Boaz P
BP
Smith
Michael L
ML
Morrison
Sean J
SJ
D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle; D016923:Cell Death; D002470:Cell Survival; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053686:Fetal Stem Cells / Q000166:cytology / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009420:Nervous System / Q000166:cytology / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C521133:Prdm16 protein, mouse; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D017228:Hepatocyte Growth Factor