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 Blood, 22 January 2009, Vol. 113, No. 4, pp. 807-815.
Prepublished online as a Blood First Edition Paper on October 16, 2008; DOI 10.1182/blood-2008-08-173682.

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HEMATOPOIESIS AND STEM CELLS

Reductive isolation from bone marrow and blood implicates common lymphoid progenitors as the major source of thymopoiesis

Thomas Serwold1,*, Lauren I. Richie Ehrlich1,*, and Irving L. Weissman13

1 Stanford Institute of Stem Cell Biology and Regenerative Medicine, 2 Ludwig Center at Stanford, and 3 Departments of Pathology and Developmental Biology, Stanford University, CA

Ongoing thymopoiesis requires continual seeding from progenitors that reside within the bone marrow (BM), but the identity of the most proximate prethymocytes has remained controversial. Here we take a comprehensive approach to prospectively identify the major source of thymocyte progenitors that reside within the BM and blood, and find that all thymocyte progenitor activity resides within a rare Flk2+CD27+ population. The BM Flk2+CD27+ subset is predominantly composed of common lymphoid progenitors (CLPs) and multipotent progenitors. Of these 2 populations, only CLPs reconstitute thymopoiesis rapidly after intravenous injection. In contrast, multipotent progenitor-derived cells reconstitute the thymus with delayed kinetics only after they have reseeded the BM, self-renewed, and generated CLPs. These results identify CLPs as the major source of thymocyte progenitors within the BM.


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