Unit for Lymphopoiesis, Pasteur Institute, Paris, France. Immunology department.
INSERM U1223, Paris, France.
Nat Immunol. 2017 Oct;18(10):1139-1149. doi: 10.1038/ni.3820. Epub 2017 Aug 21.
The molecular events that initiate lymphoid-lineage specification remain unidentified because the stages of differentiation during which lineage commitment occurs are difficult to characterize. We isolated fetal liver progenitor cells undergoing restriction of their differentiation potential toward the T cell-innate lymphoid cell lineage or the B cell lineage. Transcripts that defined the molecular signatures of these two subsets were sequentially upregulated in lympho-myeloid precursor cells and in common lymphoid progenitor cells, respectively, and this preceded lineage restriction; this indicates that T cell-versus-B cell commitment is not a binary fate 'decision'. The T cell-bias and B cell-bias transcriptional programs were frequently co-expressed in common lymphoid progenitor cells and were segregated in subsets biased toward T cell differentiation or B cell differentiation, after interleukin 7 (IL-7) signaling that controlled the number of progenitor cells engaging in T cell differentiation versus B cell differentiation.
启动淋巴谱系特化的分子事件仍未被鉴定，因为发生谱系决定的分化阶段难以被描述。我们分离了正在限制其向 T 细胞先天淋巴样细胞谱系或 B 细胞谱系分化潜能的胎肝祖细胞。分别在淋巴髓系前体细胞和共同淋巴祖细胞中，相继上调了定义这两个亚群分子特征的转录本，且该过程发生在谱系决定之前；这表明 T 细胞与 B 细胞的决定不是一个二元命运“决策”。在共同淋巴祖细胞中，T 细胞偏向性和 B 细胞偏向性转录程序经常共同表达，并在经历了控制参与 T 细胞分化与 B 细胞分化的祖细胞数量的白细胞介素 7（IL-7）信号之后，在偏向 T 细胞分化或 B 细胞分化的亚群中被分离。
