先天性淋巴细胞
祖细胞
生物
细胞生物学
祖细胞
转录因子
先天免疫系统
转录组
细胞分化
谱系(遗传)
效应器
干细胞
造血
免疫学
淋巴细胞生成
髓样
免疫系统
作者
Corey R. Seehus,Parinaz Aliahmad,Brian de la Torre,Iliyan D. Iliev,Lindsay Spurka,Vincent Funari,Jonathan Kaye
摘要
Diverse innate lymphoid cell (ILC) subtypes have been defined on the basis of effector function and transcription factor expression. ILCs derive from common lymphoid progenitors, although the transcriptional pathways that lead to ILC-lineage specification remain poorly characterized. Here we found that the transcriptional regulator TOX was required for the in vivo differentiation of common lymphoid progenitors into ILC lineage-restricted cells. In vitro modeling demonstrated that TOX deficiency resulted in early defects in the survival or proliferation of progenitor cells, as well as ILC differentiation at a later stage. In addition, comparative transcriptome analysis of bone marrow progenitors revealed that TOX-deficient cells failed to upregulate many genes of the ILC program, including genes that are targets of Notch, which indicated that TOX is a key determinant of early specification to the ILC lineage.
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