时间解析命运映射确定肠道上密室区域为Lgr5+密室基柱状细胞的来源
Claudia Capdevila1, Jonathan Miller2, Liang Cheng1
1Department of Medicine, Division of Digestive & Liver Diseases, Columbia University Irving Medical Center, New York, NY, USA; Department of Genetics & Development, Columbia University Irving Medical Center, New York, NY, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA; Digestive & Liver Diseases Research Center, Columbia University Irving Medical Center, New York, NY, USA.
Cell
|June 7, 2024
概括
新研究确定Fgfbp1+上密室细胞是产生Lgr5+细胞并驱动上皮再生的关键肠道干细胞 (ISC). 这些Fgfbp1+细胞对于维持肠道平衡至关重要.
科学领域:
- 胃肠病学
- 细胞生物学
- 发育生物学
背景情况:
- 主流模型将Lgr5+细胞确定为唯一负责上皮再生的肠干细胞 (ISC).
- Lgr5+细胞的后代通过过渡放大 (TA) 中间体向上迁移,这一过程尚未完全理解.
研究的目的:
- 识别和描述参与肠上皮再生的新细胞群.
- 为了阐明高层密室中假定TA细胞的起源和功能.
主要方法:
- 使用动力记者进行时间解决的命运映射.
- 使用Fgfbp1-CreERT2血统追踪来追踪细胞群.
- 进行转录分析以区分细胞类型.
主要成果:
- 在上层密室中发现了明显的增殖Fgfbp1+细胞群.
- 已确定Fgfbp1+细胞是产生Lgr5+细胞的多能ISC.
- 证明Fgfbp1+细胞维持上皮再生,即使Lgr5+细胞耗尽.
- 显示FGFBP1对于密码增殖和肠道平衡至关重要.
结论:
- 提出了一个修订后的模型,上面的Fgfbp1+细胞启动组织再生.
- 这些Fgfbp1+细胞产生双向迁移并补充Lgr5+细胞的后代.
- FGFBP1是维持肠表皮平衡的关键因素.
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