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The Journal of Immunology, 2001, 166: 6593-6601.
Copyright © 2001 by The American Association of Immunologists

The Fetal Liver Counterpart of Adult Common Lymphoid Progenitors Gives Rise to All Lymphoid Lineages, CD45+CD4+CD3- Cells, As Well As Macrophages1

Reina E. Mebius2,*, Toshihiro Miyamoto{dagger}, Julie Christensen{dagger}, Jos Domen{dagger}, Tom Cupedo*, Irving L. Weissman{dagger} and Koichi Akashi3,{dagger}

* Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands; and {dagger} Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305

We identified an IL-7R{alpha}+Sca-1lowc-Kitlow population in E14 fetal liver, which is the phenotypical analog of common lymphoid progenitors (CLP) in adult bone marrow. After transfer into newborn mice, the IL-7R{alpha}+Sca-1lowc-Kitlow population rapidly differentiated into CD45+CD4+CD3- cells, which are candidate cells for initiating lymph node and Peyer’s patch formation. In addition, this population also gave rise to B, T, NK, and CD8{alpha}+ and CD8{alpha}- dendritic cells. The fetal liver precursors expressed a significantly lower level of the myeloid-suppressing transcription factor Pax-5, than adult CLP, and retained differentiation activity for macrophages in vitro. We propose that the transition from fetal liver IL-7R{alpha}+Sca-1lowc-Kitlow cells to adult CLP involves a regulated restriction of their developmental potential, controlled, at least in part, by Pax-5 expression.




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