The notch pathway: modulation of cell fate decisions in hematopoiesis

Int J Hematol. 2002 Jun;75(5):449-59. doi: 10.1007/BF02982106.

Abstract

The hematopoietic system is maintained by a rare population of hematopoietic stem cells (HSC) that are thought to undergo self-renewal as well as continuously produce progeny that differentiate into the various hematopoietic lineages. However, the mechanisms regulating cell fate choices by HSC and their progeny have not been understood. Results of most studies support a stochastic model of cell fate determination in which growth factors support only the survival or proliferation of the progeny specified along a particular lineage. In other developmental systems, however, Notch signaling has been shown to play a central role in regulating fate decisions of numerous types of precursors, often inhibiting a particular (default) pathway while permitting self-renewal or differentiation along an alternative pathway. There is also accumulating evidence that the Notch pathway affects survival, proliferation, and cell fate choices at various stages of hematopoietic cell development, including the decisions of HSC to self-renew or differentiate and of common lymphoid precursors to undergo T- or B-cell differentiation. These data suggest that the Notch pathway plays a fundamental role in the development and maintenance of the hematopoietic system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation
  • Hematopoiesis / physiology*
  • Humans
  • Ligands
  • Membrane Proteins / metabolism*
  • Membrane Proteins / physiology
  • Receptors, Notch
  • Signal Transduction
  • Trans-Activators / metabolism*
  • Trans-Activators / physiology

Substances

  • Ligands
  • Membrane Proteins
  • Receptors, Notch
  • Trans-Activators