A functional screen to identify novel effectors of hematopoietic stem cell activity

Cell. 2009 Apr 17;137(2):369-79. doi: 10.1016/j.cell.2009.03.026.

Abstract

Despite tremendous progress made toward the identification of the molecular circuitry that governs cell fate in embryonic stem cells, genes controlling this process in the adult hematopoietic stem cell have proven to be more difficult to unmask. We now report the results of a novel gain-of-function screening approach, which identified a series of 18 nuclear factors that affect hematopoietic stem cell activity. Overexpression of ten of these factors resulted in an increased repopulating activity compared to unmanipulated cells. Interestingly, at least four of the 18 factors, Fos, Tcfec, Hmgb1, and Sfpi1, show non-cell-autonomous functions. The utilization of this screening method together with the creation of a database enriched for potential determinants of hematopoietic stem cell self-renewal will serve as a resource to uncover regulatory networks in these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology*
  • Adult Stem Cells / metabolism
  • Animals
  • Bone Marrow Cells
  • Cell Differentiation
  • Gene Regulatory Networks*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • NIH 3T3 Cells
  • Nuclear Proteins / analysis*
  • Specific Pathogen-Free Organisms

Substances

  • Nuclear Proteins