美国国家心肺血液研究所系统生物学中心Keji Zhao团队近期取得重要工作进展，他们研究发现转录因子TCF-1和GATA3，是早期先天性淋巴祖细胞走向不同细胞命运的表观遗传诱导的关键因素。该项研究成果2022年7月25日在线出版于《免疫》。

研究人员报告了所有淋巴祖细胞 (ALPs)、EILPs 和 ILC 前体 (ILCPs) 中不同的可接近染色质区域的鉴定。单细胞MNase-seq分析表明，EILPs包含不同的亚群，这些亚群在表观遗传上倾向于树突细胞谱系或ILC谱系。研究人员发现TCF-1和GATA3与 ILC (LDS-Is) 的谱系定义位点共同结合，而PU.1结合在替代树突细胞 (LDS-As) 的LDS中富集。TCF-1和GATA3对于EILP阶段LDS的表观遗传启动是必不可少的。

他们的研究结果表明，祖细胞的多能性是由异质细胞群的存在来定义的，这些细胞群在表观遗传上引发了不同的下游谱系，这些谱系受关键转录因子的调节。

据介绍，从造血干细胞分化出先天淋巴样细胞(ILCs)需要经历几个多能祖细胞阶段。然而，目前尚不清楚多能祖细胞的命运是否由表观遗传状态预先确定。

附：英文原文

Title: Transcription factors TCF-1 and GATA3 are key factors for the epigenetic priming of early innate lymphoid progenitors toward distinct cell fates

Author: Gang Ren, Binbin Lai, Christelle Harly, Songjoon Baek, Yi Ding, Mingzhu Zheng, Yaqiang Cao, Kairong Cui, Yu Yang, Jinfang Zhu, Gordon L. Hager, Avinash Bhandoola, Keji Zhao

Issue&Volume: 2022-07-25

Abstract: The differentiation of innate lymphoid cells (ILCs) from hematopoietic stem cellsneeds to go through several multipotent progenitor stages. However, it remains unclearwhether the fates of multipotent progenitors are predefined by epigenetic states.Here, we report the identification of distinct accessible chromatin regions in alllymphoid progenitors (ALPs), EILPs, and ILC precursors (ILCPs). Single-cell MNase-seqanalyses revealed that EILPs contained distinct subpopulations epigenetically primedtoward either dendritic cell lineages or ILC lineages. We found that TCF-1 and GATA3co-bound to the lineage-defining sites for ILCs (LDS-Is), whereas PU.1 binding wasenriched in the LDSs for alternative dendritic cells (LDS-As). TCF-1 and GATA3 wereindispensable for the epigenetic priming of LDSs at the EILP stage. Our results suggestthat the multipotency of progenitor cells is defined by the existence of a heterogeneouspopulation of cells epigenetically primed for distinct downstream lineages, whichare regulated by key transcription factors.

DOI: 10.1016/j.immuni.2022.06.019

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00292-8