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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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Submitted August 13, 2008
Accepted September 25, 2008

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

Thomas Serwold, Lauren I Richie Ehrlich*, and Irving L. Weissman

Stanford Institute of Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, United States
Stanford Ludwig Center for Stem Cell Research, Stanford University, Stanford, CA, United States

* Corresponding author; email: lauren.ehrlich{at}stanford.edu.

Ongoing thymopoiesis requires continual seeding from progenitors that reside within the bone marrow (BM), but the identity of the most proximate pre-thymocytes 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 (CLP) and multipotent progenitors (MPP). Of these two populations, only CLP reconstitute thymopoiesis rapidly after intravenous injection. In contrast, MPP-derived cells reconstitute the thymus with delayed kinetics only after they have reseeded the BM, self-renewed and generated CLP. These results identify CLP as the major source of thymocyte progenitors within the BM.


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