A dynamic niche provides Kit ligand in a stage-specific manner to the earliest thymocyte progenitors

Nat Cell Biol. 2016 Feb;18(2):157-67. doi: 10.1038/ncb3299. Epub 2016 Jan 18.


Thymic T cell development is initiated from bone-marrow-derived multi potent thymus-seeding progenitors. During the early stages of thymocyte differentiation, progenitors become T cell restricted. However, the cellular environments supporting these critical initial stages of T cell development within the thymic cortex are not known. Here we use the dependence of early, c-Kit-expressing thymic progenitors on Kit ligand (KitL) to show that CD4(-)CD8(-)c-Kit(+)CD25(-) DN1-stage progenitors associate with, and depend on, the membrane-bound form of KitL (mKitL) provided by a cortex-specific KitL-expressing vascular endothelial cell (VEC) population. In contrast, the subsequent CD4(-)CD8(-)c-Kit(+)CD25(+) DN2-stage progenitors associate selectively with cortical thymic epithelial cells (cTECs) and depend on cTEC-presented mKitL. These results show that the dynamic process of early thymic progenitor differentiation is paralleled by migration-dependent change to the supporting niche, and identify VECs as a thymic niche cell, with mKitL as a critical ligand.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation* / genetics
  • Cell Lineage
  • Cell Movement* / genetics
  • Cells, Cultured
  • Coculture Techniques
  • Endothelial Cells / metabolism*
  • Gene Expression Regulation, Developmental
  • Mice, Transgenic
  • Multipotent Stem Cells / metabolism*
  • Paracrine Communication* / genetics
  • Phenotype
  • Signal Transduction
  • Stem Cell Factor / genetics
  • Stem Cell Factor / metabolism*
  • Stem Cell Niche*
  • Thymocytes / metabolism*


  • Stem Cell Factor