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

Published in: Immunity 2017 Oct; 47(4): 680-696.e8

Authors: Kutaiba Alhaj Hussen, Thien-Phong Vu Manh, Fabien Guimiot, Elisabeth Nelson, Emna Chabaane, Marc Delord, Maxime Barbier, Claire Berthault, Nicolas Dulphy, Antonio José Alberdi, Odile Burlen-Defranoux, Gérard Socié, Jean Christophe Bories, Jerome Larghero, Valérie Vanneaux, Els Verhoeyen, Thierry Wirth, Marc Dalod, Jean Claude Gluckman, Ana Cumano, Bruno Canque

Summary

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.

Link to Pubmed [PMID] – 29045900

Link to HAL – inserm-01624830

Link to DOI – 10.1016/j.immuni.2017.09.009