A developmental switch in thymic lymphocyte maturation potential occurs at the level of hematopoietic stem cells

TLDR

Mouse fetal liver HSCs share the Thy‑1lo Lin‑ Sca‑1+ phenotype with adult HSCs. Fetal HSCs, but not adult HSCs, generate Vγ3⁺ T cells in the fetal thymus, and neither fetal nor adult HSCs produce these cells in adult thymus, indicating a developmental switch in HSC differentiation potential during ontogeny.

Abstract

Hematopoietic stem cells (HSCs) isolated from mouse fetal liver, like adult HSCs, are Thy-1lo Lin- Sca-1+. Donor-derived V gamma 3+ T cells were detected in fetal thymic lobes repopulated in vitro with fetal liver HSCs, but not in those with adult bone marrow HSCs. Single clonogenic fetal HSCs gave rise to thymic progeny that include V gamma 3+, other gamma delta+, and alpha beta+ T cells. No V gamma 3+ T cells were detected in adult thymus injected intrathymically with either fetal or adult HSCs. These results support the hypothesis that only fetal HSCs have the capacity to differentiate into V gamma 3+ T cells in the fetal thymic microenvironment and that the developmental potential of HSCs may change during ontogeny.