Notch-dependent T-lineage commitment occurs at extrathymic sites following bone marrow transplantation

I Maillard, BA Schwarz, A Sambandam, T Fang… - Blood, 2006 - ashpublications.org
I Maillard, BA Schwarz, A Sambandam, T Fang, O Shestova, L Xu, A Bhandoola, WS Pear
Blood, 2006ashpublications.org
Early T-lineage progenitors (ETPs) arise after colonization of the thymus by multipotent bone
marrow progenitors. ETPs likely serve as physiologic progenitors of T-cell development in
adult mice, although alternative T-cell differentiation pathways may exist. While we were
investigating mechanisms of T-cell reconstitution after bone marrow transplantation (BMT),
we found that efficient donor-derived thymopoiesis occurred before the pool of ETPs had
been replenished. Simultaneously, T lineage–restricted progenitors were generated at …
Early T-lineage progenitors (ETPs) arise after colonization of the thymus by multipotent bone marrow progenitors. ETPs likely serve as physiologic progenitors of T-cell development in adult mice, although alternative T-cell differentiation pathways may exist. While we were investigating mechanisms of T-cell reconstitution after bone marrow transplantation (BMT), we found that efficient donor-derived thymopoiesis occurred before the pool of ETPs had been replenished. Simultaneously, T lineage–restricted progenitors were generated at extrathymic sites, both in the spleen and in peripheral lymph nodes, but not in the bone marrow or liver. The generation of these T lineage–committed cells occurred through a Notch-dependent differentiation process. Multipotent bone marrow progenitors efficiently gave rise to extrathymic T lineage–committed cells, whereas common lymphoid progenitors did not. Our data show plasticity of T-lineage commitment sites in the post-BMT environment and indicate that Notch-driven extrathymic Tlineage commitment from multipotent progenitors may contribute to early T-lineage reconstitution after BMT.
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