C/EBPa controls acquisition and maintenance of adult hematopoietic stem cell quiescence

Details

• Alternative Title:
  Nat Cell Biol
• Personal Author:
  Ye, Min ; Zhang, Hong ; Amabile, Giovanni ; Yang, Henry ; Staber, Philipp B. ; Zhang, Pu ; Levantini, Elena ; Alberich-Jordà, Meritxell ; Zhang, Junyan ; Kawasaki, Akira ; Tenen, Daniel G.
• Description:
  In blood, the transcription factor C/EBPa is essential for myeloid differentiation and has been implicated in regulating self-renewal of fetal liver haematopoietic stem cells (HSCs). However, its function in adult HSCs has remained unknown. Here, using an inducible knockout model we found that C/EBPa-deficient adult HSCs underwent a pronounced increase in number with enhanced proliferation, characteristics resembling fetal liver HSCs. Consistently, transcription profiling of C/EBPa-deficient HSCs revealed a gene expression program similar to fetal liver HSCs. Moreover, we observed that age-specific Cebpa expression correlated with its inhibitory effect on the HSC cell cycle. Mechanistically we identified N-Myc as a downstream target of C/EBPa, and loss of C/EBPa resulted in de-repression of N-Myc. Our data establish C/EBPa as a central determinant in the switch from fetal to adult HSCs.
• Subjects:
  Adult Stem Cells Animals Apoptosis Article Biomarkers, Tumor Blotting, Western Bone Marrow Transplantation C/EBPa CCAAT-Enhancer-Binding Proteins Cell Cycle Cell Differentiation Cell Proliferation Chromatin Immunoprecipitation Fetal Stem Cells Flow Cytometry Gene Expression Profiling Hematopoietic Stem Cell Hematopoietic Stem Cells Integrases Luciferases Mice Mice, Knockout N-Myc Oligonucleotide Array Sequence Analysis Proliferation Proto-Oncogene Proteins C-myc Quiescence Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Transcription Factor

  More +
• Source:
  Nat Cell Biol. 15(4):385-394.
• Pubmed ID:
  23502316
• Pubmed Central ID:
  PMC3781213
• Document Type:
  Journal Article
• Funding:
  K01 DP000086/DP/NCCDPHP CDC HHS/United States ; R01 CA118316/CA/NCI NIH HHS/United States ; HL 56745/HL/NHLBI NIH HHS/United States ; P01 CA066996/CA/NCI NIH HHS/United States ; R01 HL056745/HL/NHLBI NIH HHS/United States ; R01 CA041456/CA/NCI NIH HHS/United States ; R01 HL112719/HL/NHLBI NIH HHS/United States ; T32 HL007917/HL/NHLBI NIH HHS/United States
• Volume:
  15
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:ca36d0ead5cff246d5fcf0036a8bd30ed7ab9bb80a52c99b1aa525afa8020e83
• Download URL:
  https://stacks.cdc.gov/view/cdc/41917/cdc_41917_DS1.pdf
• File Type:
  [PDF - 1.73 MB ]