肠道分泌分化反映了一个常见的信号响应终端细胞的利基驱动的表型和表观遗传可塑性
Swarnabh Bhattacharya1, Guodong Tie2, Pratik N P Singh1
1Department of Medical Oncology and Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Cell stem cell
|April 9, 2025
概括
肠道中的戈布莱特细胞和帕内斯细胞具有许多共同的分子特征,这表明它们来自一种共同的细胞类型. 利基信号,如Wnt和BMP通路,驱动它们的独特特征和抗微生物基因表达.
科学领域:
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
背景情况:
- 肠上皮干细胞分化成各种细胞类型,包括肠细胞和四种分泌细胞类型.
- 古布莱特细胞和帕内特细胞传统上被视为基于形态和标记物的独特分泌细胞系.
研究的目的:
- 为了研究玻璃杯和帕内斯细胞之间的分子关系和潜在的可塑性.
- 了解信号通路和利基环境在确定肠道分泌细胞表型中的作用.
主要方法:
- 鼠标和人类杯子和帕内斯细胞的比较转录基因分析.
- 染色体可访问性分析,以确定监管要素.
- 对信号通路参与 (Wnt,BMP) 在细胞命运决定中的分析.
主要成果:
- 玻璃杯和帕内斯细胞在基因表达和染色质可访问性方面表现出显著的重叠,与肠内分泌或细胞不同.
- 这两种细胞类型都表达出高比例的抗微生物基因,这表明了利基特异性反应.
- Wnt信号维护了密室底部的细胞,而BMP信号则促进了从密室中分离的杯状细胞,而其缺失则促进了帕内斯细胞的特征.
结论:
- 玻璃杯和帕内特细胞表型不是固定的,而是代表一个常见的信号响应细胞类型的相互可转换状态.
- 利基依赖信号通路 (Wnt,BMP) 在肠表皮中协调细胞可塑性和 cis 调节动力学.
- 这些发现凸显了肠道细胞在应对局部抗微生物需求时的适应性.
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