美国丹娜-法伯癌症研究所Ramesh A. Shivdasani等研究人员合作揭示人类肠内分泌细胞分化过程中转录因子的动态、振荡和功能。该研究于2024年5月10日在线发表于国际一流学术期刊《细胞—干细胞》。

据了解，EEC分泌血清素（EC细胞）或特定的肽类激素（非EC细胞），发挥着重要的新陈代谢功能。终端EEC多样性的基础仍然模糊不清。

附：英文原文

Title: Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation

Author: Pratik N.P. Singh, Wei Gu, Shariq Madha, Allen W. Lynch, Paloma Cejas, Ruiyang He, Swarnabh Bhattacharya, Miguel Muoz Gomez, Matthew G. Oser, Myles Brown, Henry W. Long, Clifford A. Meyer, Qiao Zhou, Ramesh A. Shivdasani

Issue&Volume: 2024-05-10

Abstract: Enteroendocrine cells (EECs) secrete serotonin (enterochromaffin [EC] cells) or specificpeptide hormones (non-EC cells) that serve vital metabolic functions. The basis forterminal EEC diversity remains obscure. By forcing activity of the transcription factor(TF) NEUROG3 in 2D cultures of human intestinal stem cells, we replicated physiologicEEC differentiation and examined transcriptional and cis-regulatory dynamics that culminate in discrete cell types. Abundant EEC precursorsexpressed stage-specific genes and TFs. Before expressing pre-terminal NEUROD1, post-mitoticprecursors oscillated between transcriptionally distinct ASCL1+ and HES6hi cell states. Loss of either factor accelerated EEC differentiation substantiallyand disrupted EEC individuality; ASCL1 or NEUROD1 deficiency had opposing consequenceson EC and non-EC cell features. These TFs mainly bind cis-elements that are accessible in undifferentiated stem cells, and they tailor subsequentexpression of TF combinations that underlie discrete EEC identities. Thus, early TFoscillations retard EEC maturation to enable accurate diversity within a medicallyimportant cell lineage.

DOI: 10.1016/j.stem.2024.04.015

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00142-5