细胞内pH动力学调节肠道干细胞谱系规范 肠道干细胞谱系规范
Yi Liu1, Efren Reyes2, David Castillo-Azofeifa2,3
1Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA, 94143, USA.
Nature communications
|June 23, 2023
概括
细胞内pH梯度调节老鼠肠道中成年干细胞的命运. 破坏这种pH梯度会阻断干细胞芽和帕内斯细胞分化,这对肠道维护至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 干细胞生物学 干细胞生物学
- 胃肠道生理学 胃肠道生理学
背景情况:
- 细胞内pH动态是各种细胞功能的关键调节者.
- 成人干细胞谱系的规范对于组织恒温和再生至关重要.
- 细胞内pH在成年干细胞命运决定中的作用在很大程度上仍未被探索.
研究的目的:
- 为了研究细胞内pH动态在成年干细胞谱系规范中的作用,在小鼠小肠密室内.
- 确定参与pH介导干细胞命运决定的特定机制和分子参与者.
主要方法:
- 利用小鼠小肠来分析细胞内pH梯度.
- 采用Na+/H+交换器1 (NHE1) 抑制来破坏pH梯度.
- 应用外部WNT来评估救援效应.
- 进行单细胞RNA测序和谱系追踪以阐明分子通路.
主要成果:
- 在肠道密室中确定了明显的细胞内pH梯度,在干细胞中最低,沿密室轴增加.
- 通过NHE1废除了密室芽和Paneth细胞分化来抑制H+流量.
- 外源性WNT治疗挽救了观察到的密室芽和Paneth细胞分化的缺陷.
- 证明细胞内pH动态作用于ATOH1的下游,高pH促进分泌系的分化.
结论:
- 细胞内pH动态在调节肠道密室中成年干细胞谱系规范方面发挥着至关重要的作用.
- 细胞内pH值的增加对于血统规范至关重要,有助于密室维护.
- 这些发现确立了细胞内pH动态在管理成年干细胞群体内的细胞命运决定中的新角色.
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