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De novo generation of T cells depends on continual colonization of the thymus by bone marrow-derived progenitors. Thymus
seeding progenitors (TSPs) constitute a heterogeneous population comprising multipotent and lineage-restricted cell types.
Entry into the thymic microenvironment is tightly controlled and recent quantitative studies have revealed that the adult
murine thymus only contains approximately 160 niches to accommodate TSPs. Of these niches only about 6% are open for
seeding on average at steady-state. Here, I review the state of understanding of colonization of the adult murine thymus with
a particular focus on past and current controversies in the field. Improving thymus colonization and/or maintaining intact
TSP niches during the course of pre-conditioning regimens are likely to be critical for efficient T-cell regeneration after
hematopoietic stem cell transplantation.