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

Abstract：

: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.

journal_name

Immunity

journal_title

Immunity

authors

Alhaj Hussen K,Vu Manh TP,Guimiot F,Nelson E,Chabaane E,Delord M,Barbier M,Berthault C,Dulphy N,Alberdi AJ,Burlen-Defranoux O,Socié G,Bories JC,Larghero J,Vanneaux V,Verhoeyen E,Wirth T,Dalod M,Gluckman JC,Cumano A

doi

10.1016/j.immuni.2017.09.009

subject

Has Abstract

pub_date

2017-10-17 00:00:00

pages

680-696.e8

issue

4

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(17)30420-X

journal_volume

47

pub_type

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