一个对肠道分泌物分化的修订模型的利基驱动的表型可塑性和cis-regulatory动态
bioRxiv : the preprint server for biology
|February 20, 2025
概括
肠道中的玻璃杯和帕内斯细胞不是不同的,而是可以互换的细胞类型. 它们的特性是由利基信号决定的,揭示了肠道上皮的显著细胞可塑性.
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:
- 肠上皮细胞,包括肠细胞和四种分泌细胞类型,起源于密室中的干细胞.
- 古布莱特细胞和帕内特细胞传统上被视为不同的分泌细胞系.
研究的目的:
- 为了研究玻璃杯和帕内斯细胞之间的关系和潜在的可塑性.
- 探索肠道分泌细胞分化背后的调节机制.
主要方法:
- 肠道分泌细胞的比较转录基因分析.
- 在小鼠和人类肠道组织中进行染色体可访问性分析 (ATAC-seq).
- 对与Wnt和BMP信号通路相关的基因表达模式的分析.
主要成果:
- 玻璃杯和帕内斯细胞在转录和可访问的染色质中表现出显著的重叠,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,对利基信号作出动态反应.
- Wnt信号促进了密室底部的ATOH1+分泌细胞,而BMP信号的缺失诱导了Paneth细胞特征;接近密室底部驱动了杯细胞特征.
- 细胞表型和 cis 调节元件表明了相互可转换性.
结论:
- 杯子和帕内特细胞的特性代表单一的多功能分泌细胞类型的替代状态.
- 肠上皮细胞分化的特点是显著的利基依赖可塑性.
- 这些发现支持肠道上皮质谱系发展的更新的单元模型,强调cis-regulatory动态.
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