美国丹娜-法伯癌症研究所Ramesh A. Shivdasani研究组发现了肠道分泌分化反映了一个共同的信号响应终端细胞的生态位驱动的表型和表观遗传可塑性。这一研究成果于2025年4月8日发表在国际顶尖学术期刊《细胞—干细胞》上。

研究组报告了它们的转录本和可接近染色质位点的高度重叠，与它们的肠内分泌或簇状细胞兄弟姐妹形成鲜明对比。小鼠和人类杯状细胞和Paneth细胞表达少数抗菌基因的特殊部分，这反映了对当地生态位的特定反应。Wnt信号在隐窝底部保留了一些ATOH1⁺分泌细胞，在那里缺乏BMP信号可能会诱导Paneth特征。从隐窝底部迁移的细胞遇到BMP，从而获得高脚杯特性。这些表型和潜在的可接近的顺式元件在有丝分裂后的细胞中相互转换。因此，杯状物和Paneth特性代表了一种常见信号反应终端细胞类型的替代表型表现。这些发现揭示了精致的小生境依赖性细胞可塑性和顺式调控动力学可能对抗菌需求的反应。

研究人员表示，肠细胞及其典型的分泌细胞类型来源于肠上皮干细胞。基于形态、位置和典型标记，杯状细胞和Paneth细胞被认为是不同的分泌类型。

附：英文原文

Title: Intestinal secretory differentiation reflects niche-driven phenotypic and epigenetic plasticity of a common signal-responsive terminal cell

Author: Swarnabh Bhattacharya, Guodong Tie, Pratik N.P. Singh, Ermanno Malagola, Onur Eskiocak, Ruiyang He, Judith Kraiczy, Wei Gu, Yakov Perlov, Aybuke Alici-Garipcan, Semir Beyaz, Timothy C. Wang, Qiao Zhou, Ramesh A. Shivdasani

Issue&Volume: 2025-04-08

Abstract: Enterocytes and four classic secretory cell types derive from intestinal epithelial stem cells. Based on morphology, location, and canonical markers, goblet and Paneth cells are considered distinct secretory types. Here, we report high overlap in their transcripts and sites of accessible chromatin, in marked contrast to those of their enteroendocrine or tuft cell siblings. Mouse and human goblet and Paneth cells express extraordinary fractions of few antimicrobial genes, which reflect specific responses to local niches. Wnt signaling retains some ATOH1+ secretory cells in crypt bottoms, where the absence of BMP signaling potently induces Paneth features. Cells that migrate away from crypt bottoms encounter BMPs and thereby acquire goblet properties. These phenotypes and underlying accessible cis-elements interconvert in post-mitotic cells. Thus, goblet and Paneth properties represent alternative phenotypic manifestations of a common signal-responsive terminal cell type. These findings reveal exquisite niche-dependent cell plasticity and cis-regulatory dynamics in likely response to antimicrobial needs.

DOI: 10.1016/j.stem.2025.03.005

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00095-5