INSERM U1126, Université Paris-Diderot, École Pratique des Hautes Etudes/PSL Research University, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.
Aix Marseille Univ, CNRS, INSERM, CIML, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
Immunity. 2017 Oct 17;47(4):680-696.e8. doi: 10.1016/j.immuni.2017.09.009.
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.
造血的经典模型是在小鼠中建立的，该模型假设淋巴细胞起源于一个共同淋巴祖细胞的创始群体。在这里，我们使用人类化小鼠的建模方法表明，人类淋巴样发育源于 CD127 和 CD127 早期淋巴祖细胞（ELP）的不同群体。通过结合分子分析以及体外和体内功能测定，我们证明 CD127 和 CD127 ELP 独立于淋巴单核树突状祖细胞产生，对 Notch1 信号的反应不同，经历不同的谱系限制模式，并表现出共同和特定的分化潜能。虽然 CD127 ELP 包含 T 细胞、边缘区 B 细胞以及自然杀伤（NK）和先天淋巴样细胞（ILC）的前体，但 CD127 ELP 支持所有 NK 细胞、ILC 和 B 细胞群体的产生，但缺乏 T 细胞潜能。基于这些结果，我们提出了一个“两大家族”的人类淋巴样发育模型，与造血的主流模型不同。
