In vivo mapping of notch pathway activity in normal and stress hematopoiesis

Cell Stem Cell. 2013 Aug 1;13(2):190-204. doi: 10.1016/j.stem.2013.05.015. Epub 2013 Jun 20.


Accumulating evidence suggests that Notch signaling is active at multiple points during hematopoiesis. Until recently, the majority of such studies focused on Notch signaling in lymphocyte differentiation and knowledge of individual Notch receptor roles has been limited due to a paucity of genetic tools available. In this manuscript we generate and describe animal models to identify and fate-map stem and progenitor cells expressing each Notch receptor, delineate Notch pathway activation, and perform in vivo gain- and loss-of-function studies dissecting Notch signaling in early hematopoiesis. These models provide comprehensive genetic maps of lineage-specific Notch receptor expression and activation in hematopoietic stem and progenitor cells. Moreover, they establish a previously unknown role for Notch signaling in the commitment of blood progenitors toward the erythrocytic lineage and link Notch signaling to optimal organismal response to stress erythropoiesis.

Publication types

  • Research Support, N.I.H., Extramural
  • 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 Differentiation / genetics
  • Cell Division
  • Cell Lineage / genetics
  • Erythroid Cells / cytology
  • Erythroid Cells / metabolism
  • Fetus / cytology
  • Gene Expression Profiling
  • Genes, Reporter
  • Hematopoiesis*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Mice
  • Models, Biological
  • Receptor, Notch1 / metabolism*
  • Receptor, Notch2 / metabolism*
  • Signal Transduction*
  • Stress, Physiological* / genetics
  • Transcription Factor HES-1
  • Transcription, Genetic


  • Basic Helix-Loop-Helix Transcription Factors
  • Hes1 protein, mouse
  • Homeodomain Proteins
  • Receptor, Notch1
  • Receptor, Notch2
  • Transcription Factor HES-1