The mouse thymus supports T-cell development, but also contains non-T-cell lineages such as dendritic cells (DC), macrophages, and granulocytes that are necessary for T-cell repertoire selection and apoptotic thymocyte clearance. Early thymic progenitors (ETP) are not committed to the T-cell lineage as demonstrated by both in vitro and in vivo assays. Whether ETP realize non-T-cell lineage potentials in vivo is not well understood and indeed controversial. Here, we examine whether ETP are the major precursors of any non-T-lineage cells in the thymus. We analyzed development of these populations under experimental circumstances in which ETP are nearly absent, either due to abrogated thymic settling, or due to inhibition of early thymic development by genetic ablation of IL-7Rα or Hes1. Results obtained using multiple in vivo approaches indicate that the majority of thymic granulocytes derive from ETP. These data indicate that myelo-lymphoid progenitors settle the thymus, and thus clarify the pathways by which stem cells give rise to downstream blood cell lineages.
- Submitted August 27, 2012.
- Accepted October 15, 2012.
- Copyright © 2005 American Society of Hematology