3 years ago

Molecular and Functional Characterization of Lymphoid Progenitor Subsets Reveals a Bipartite Architecture of Human Lymphopoiesis

Molecular and Functional Characterization of Lymphoid Progenitor Subsets Reveals a Bipartite Architecture of Human Lymphopoiesis
Jean Christophe Bories, Claire Berthault, Jean Claude Gluckman, Marc Dalod, Odile Burlen-Defranoux, Emna Chabaane, Bruno Canque, Thierry Wirth, Marc Delord, Nicolas Dulphy, Gerard Socié, Antonio José Alberdi, Elisabeth Nelson, Thien-Phong Vu Manh, Valérie Vanneaux, Maxime Barbier, Jerôme Larghero, Kutaiba Alhaj Hussen, Els Verhoeyen, Ana Cumano, Fabien Guimiot


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.

Publisher URL: http://www.cell.com/immunity/fulltext/S1074-7613(17)30420-X

DOI: 10.1016/j.immuni.2017.09.009

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