Mapping Differentiation Pathways From Hematopoietic Stem Cells Using Flk2/Flt3 Lineage Tracing

Cell Cycle. 2012 Sep 1;11(17):3180-8. doi: 10.4161/cc.21279. Epub 2012 Aug 16.

Abstract

Genetic fate-mapping approaches provide a unique opportunity to assess differentiation pathways under physiological conditions. We have recently employed a lineage tracing approach to define hematopoietic differentiation pathways in relation to expression of the tyrosine kinase receptor Flk2.1 Based on our examination of reporter activity across all stem, progenitor and mature populations in our Flk2-Cre lineage model, we concluded that all mature blood lineages are derived through a Flk2+ intermediate, both at steady-state and under stress conditions. Here, we re-examine in depth our initial conclusions and perform additional experiments to test alternative options of lineage specification. Our data unequivocally support the conclusion that onset of Flk2 expression results in loss of self-renewal but preservation of multilineage differentiation potential. We discuss the implications of these data for defining stem cell identity and lineage potential among hematopoietic populations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cell Lineage / physiology*
  • Flow Cytometry
  • Gene Expression Regulation, Developmental / physiology*
  • Gene Transfer Techniques
  • Green Fluorescent Proteins
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / physiology
  • Mice
  • Models, Biological
  • fms-Like Tyrosine Kinase 3 / metabolism*

Substances

  • Green Fluorescent Proteins
  • Flt3 protein, mouse
  • fms-Like Tyrosine Kinase 3