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Blood, 15 June 2008, Vol. 111, No. 12, pp. 5562-5570.
Prepublished online as a Blood First Edition Paper on April 18, 2008; DOI 10.1182/blood-2007-11-126219.
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Submitted November 29, 2007
Accepted March 27, 2008
Flk2+ common lymphoid progenitors possess equivalent differentiation potential for the B and T lineages
Holger Karsunky*, Matthew A Inlay, Thomas Serwold, Deepta Bhattacharya, and Irving L Weissman
Department of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA, United States
* Corresponding author; email: karsunky{at}sbcglobal.net.
Mature blood cells develop from multipotent hematopoietic stem cells through a series of sequential intermediates in which the developmental potential for particular blood lineages is progressively extinguished. We previously reported the identification of one of these developmental intermediates, the common lymphoid progenitor (CLP), which can give rise to T, B, dendritic, and NK cells but lacks myeloid and erythroid potential. Recently, several studies, have suggested that the T and dendritic cell potential of CLP is limited or absent, and/or that CLP contain significant myeloid potential. Here, we show that the originally identified CLP population can be divided into functionally distinct subsets based on the expression of the tyrosine kinase receptor, Flk2. The Flk2+ subset, contains robust in vivo and in vitro T, B, DC, and NK potential, but lacks myeloid potential and therefore, represents an oligopotent, lymphoid-restricted progenitor. This population of cells does not appear to be B cell-biased and robustly reconstitutes both B and T lineages in vivo, consistent with it being a physiological progenitor of both of these subsets. Thus, Flk2 expression defines a homogeneous, readily obtainable subset of bone marrow CLP that is completely lymphoid committed and can differentiate equivalently well into both B and T lineages.
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