Scl regulates the quiescence and the long-term competence of hematopoietic stem cells

Blood. 2010 Jan 28;115(4):792-803. doi: 10.1182/blood-2009-01-201384. Epub 2009 Oct 22.


The majority of long-term reconstituting hematopoietic stem cells (LT-HSCs) in the adult is in G(0), whereas a large proportion of progenitors are more cycling. We show here that the SCL/TAL1 transcription factor is highly expressed in LT-HSCs compared with short-term reconstituting HSCs and progenitors and that SCL negatively regulates the G(0)-G(1) transit of LT-HSCs. Furthermore, when SCL protein levels are decreased by gene targeting or by RNA interference, the reconstitution potential of HSCs is impaired in several transplantation assays. First, the mean stem cell activity of HSCs transplanted at approximately 1 competitive repopulating unit was 2-fold decreased when Scl gene dosage was decreased. Second, Scl(+/-) HSCs were at a marked competitive disadvantage with Scl(+/+) cells when transplanted at 4 competitive repopulating units equivalent. Third, reconstitution of the stem cell pool by adult HSCs expressing Scl-directed shRNAs was decreased compared with controls. At the molecular level, we found that SCL occupies the Cdkn1a and Id1 loci in primary hematopoietic cells and that the expression levels of these 2 regulators of HSC cell cycle and long-term functions are sensitive to Scl gene dosage. Together, our observations suggest that SCL impedes G(0)-G(1) transition in HSCs and regulates their long-term competence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • G1 Phase / physiology
  • Gene Expression / physiology
  • Graft Survival
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / physiology*
  • Inhibitor of Differentiation Protein 1 / genetics
  • Interleukin-11 / pharmacology
  • Interleukin-6 / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism*
  • RNA Interference
  • Resting Phase, Cell Cycle / physiology
  • Stem Cell Factor / pharmacology
  • T-Cell Acute Lymphocytic Leukemia Protein 1


  • Basic Helix-Loop-Helix Transcription Factors
  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Idb1 protein, mouse
  • Inhibitor of Differentiation Protein 1
  • Interleukin-11
  • Interleukin-6
  • Proto-Oncogene Proteins
  • Stem Cell Factor
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Tal1 protein, mouse