期刊
IMMUNITY
卷 47, 期 4, 页码 680-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2017.09.009
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类别
资金
- Agence de la Biomedecine
- Universite Paris-Diderot
- Comite de Paris de la Ligue contre le Cancer
- Institut National du Cancer
- Fondation Ramsay Generale de Sante
- Fondation pour la Recherche Medicale
The classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127(-) and CD127(+) early lymphoid progenitors (ELPs). Combining molecular analyses with in vitro and in vivo functional assays, we demonstrated that CD127(-) and CD127+ ELPs emerged independently from lympho-mono-dendritic progenitors, responded differently to Notch1 signals, underwent divergent modes of lineage restriction, and displayed both common and specific differentiation potentials. Whereas CD127(-) ELPs comprised precursors of T cells, marginal zone B cells, and natural killer (NK) and innate lymphoid cells (ILCs), CD127(+) ELPs supported production of all NK cell, ILC, and B cell populations but lacked T potential. On the basis of these results, we propose a two-family'' model of human lymphoid development that differs from the prevailing model of hematopoiesis.
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