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Cell fate specification and differentiation in the adult mammalian intestine. ​

文献信息 ​

DOI10.1038/s41580-020-0278-0
PMID32958874
期刊Nature reviews. Molecular cell biology
影响因子90.2
JCR 分区Q1
发表年份2021
被引次数291
关键词肠道干细胞, 细胞命运特化, 组织再生
文献类型Journal Article, Review
ISSN1471-0072
页码39-53
期号22(1)
作者Joep Beumer, Hans Clevers

一句话小结 ​

本研究揭示了肠道干细胞的谱系可塑性及其在组织修复中的重要性，表明环境信号能诱导干细胞形成六种不同的肠道细胞谱系。此发现为利用肠道再生能力开发新的治疗方法提供了潜在的依据。

在麦伴科研 (maltsci.com) 搜索更多文献 ​

肠道干细胞 · 细胞命运特化 · 组织再生

摘要 ​

肠道干细胞位于隐窝底部，驱动着构成多任务组织的不同细胞类型的快速更新。肠上皮不仅促进营养物质的选择性吸收，还充当抵御有害腔内物质的屏障。近期的发现揭示，承诺细胞的谱系可塑性，加上冗余的生态位信号来源，使得上皮能够高效修复组织损伤。单细胞转录组学和类器官模型等新方法的应用，促使研究人员识别出引导干细胞后代命运特定形成六种肠道细胞谱系的信号。这些细胞类型展现出依赖于环境的功能性，并能够根据微环境的要求在其生命周期内进行适应。这些关于干细胞调控和命运特定的新见解可能有助于开发利用肠道再生能力和功能性的治疗方法。

英文摘要 ​

Intestinal stem cells at the bottom of crypts fuel the rapid renewal of the different cell types that constitute a multitasking tissue. The intestinal epithelium facilitates selective uptake of nutrients while acting as a barrier for hostile luminal contents. Recent discoveries have revealed that the lineage plasticity of committed cells - combined with redundant sources of niche signals - enables the epithelium to efficiently repair tissue damage. New approaches such as single-cell transcriptomics and the use of organoid models have led to the identification of the signals that guide fate specification of stem cell progeny into the six intestinal cell lineages. These cell types display context-dependent functionality and can adapt to different requirements over their lifetime, as dictated by their microenvironment. These new insights into stem cell regulation and fate specification could aid the development of therapies that exploit the regenerative capacity and functionality of the gut.

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主要研究问题 ​

  1. 成体哺乳动物肠道中的干细胞如何受到微环境信号的影响以决定细胞命运？
  2. 在肠道上皮中，承诺细胞的谱系可塑性是如何促进组织修复的？
  3. 单细胞转录组学在识别肠道干细胞后代命运规范信号方面发挥了哪些具体作用？
  4. 有哪些新的治疗策略可以利用肠道干细胞的再生能力来治疗相关疾病？
  5. 不同肠道细胞类型的功能如何根据其微环境的变化而适应？

核心洞察 ​

1. 研究背景和目的 ​

成人哺乳动物的肠道是一个复杂的多功能组织，其表面由多种细胞类型组成。这些细胞类型的快速更新主要依赖于肠道干细胞，这些干细胞位于肠道隐窝的底部。肠道上皮不仅负责选择性营养物质的吸收，还充当对抗有害内容物的屏障。因此，研究肠道干细胞的命运决定和分化过程对于理解肠道的再生能力和功能至关重要。本研究旨在揭示肠道干细胞及其后代细胞的命运决定机制，以便为开发新型治疗方法提供理论基础。

2. 主要方法和发现 ​

本研究采用了单细胞转录组学和类器官模型等新方法，对肠道干细胞的分化过程进行了深入分析。研究发现，承诺细胞的谱系可塑性与冗余的微环境信号来源相结合，使得肠道上皮能够高效修复组织损伤。通过这些方法，研究识别了指导肠道干细胞后代命运决定的信号，这些后代细胞能分化为六种不同的肠道细胞谱系。这些细胞类型在功能上表现出依赖于环境的适应性，能够根据微环境的变化满足不同的生理需求。

3. 核心结论 ​

研究表明，肠道干细胞的命运决定是一个受多种信号调控的复杂过程，细胞谱系的可塑性和微环境的信号在其中发挥了关键作用。这种机制使得肠道上皮能够快速响应损伤并进行有效修复，展现了其卓越的再生能力。

4. 研究意义和影响 ​

本研究的发现为理解肠道再生和损伤修复提供了新的视角，揭示了肠道干细胞及其后代细胞在适应性和功能性方面的灵活性。这些洞察不仅丰富了我们对肠道生物学的理解，还为未来的治疗策略提供了潜在的靶点，有助于开发针对肠道疾病的再生医学方法，进一步推动临床应用的发展。通过利用肠道的再生能力，未来可能会在治疗肠道疾病、促进组织修复方面取得重要进展。

参考文献 ​

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  5. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian Theory of the origin of the four epithelial cell types. - H Cheng;C P Leblond - The American journal of anatomy (1974)
  6. Clonal analysis of mouse intestinal epithelial progenitors. - M Bjerknes;H Cheng - Gastroenterology (1999)
  7. A clonal marker induced by mutation in mouse intestinal epithelium. - D J Winton;M A Blount;B A Ponder - Nature (1988)
  8. Identification of stem cells in small intestine and colon by marker gene Lgr5. - Nick Barker;Johan H van Es;Jeroen Kuipers;Pekka Kujala;Maaike van den Born;Miranda Cozijnsen;Andrea Haegebarth;Jeroen Korving;Harry Begthel;Peter J Peters;Hans Clevers - Nature (2007)
  9. Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium. - François Gerbe;Johan H van Es;Leila Makrini;Bénédicte Brulin;Georg Mellitzer;Sylvie Robine;Béatrice Romagnolo;Noah F Shroyer;Jean-François Bourgaux;Christine Pignodel;Hans Clevers;Philippe Jay - The Journal of cell biology (2011)
  10. Peyer's patch M cells derived from Lgr5(+) stem cells require SpiB and are induced by RankL in cultured "miniguts". - Wim de Lau;Pekka Kujala;Kerstin Schneeberger;Sabine Middendorp;Vivian S W Li;Nick Barker;Anton Martens;Frans Hofhuis;Rodney P DeKoter;Peter J Peters;Edward Nieuwenhuis;Hans Clevers - Molecular and cellular biology (2012)

引用本文的文献 ​

  1. Organoid-based modeling of intestinal development, regeneration, and repair. - Joep Sprangers;Irene C Zaalberg;Madelon M Maurice - Cell death and differentiation (2021)
  2. The Hippo-YAP Signaling as Guardian in the Pool of Intestinal Stem Cells. - Yoojin Seo;So-Yeon Park;Hyung-Sik Kim;Jeong-Seok Nam - Biomedicines (2020)
  3. The 3D Pattern of the Rainbow Trout (Oncorhynchus mykiss) Enterocytes and Intestinal Stem Cells. - Nicole Verdile;Rolando Pasquariello;Tiziana A L Brevini;Fulvio Gandolfi - International journal of molecular sciences (2020)
  4. A bioengineering perspective on modelling the intestinal epithelial physiology in vitro. - Maria Antfolk;Kim B Jensen - Nature communications (2020)
  5. Cytoskeletal Control and Wnt Signaling-APC's Dual Contributions in Stem Cell Division and Colorectal Cancer. - M Angeles Juanes - Cancers (2020)
  6. Spatiotemporal analysis of human intestinal development at single-cell resolution. - David Fawkner-Corbett;Agne Antanaviciute;Kaushal Parikh;Marta Jagielowicz;Ana Sousa Gerós;Tarun Gupta;Neil Ashley;Doran Khamis;Darren Fowler;Edward Morrissey;Chris Cunningham;Paul R V Johnson;Hashem Koohy;Alison Simmons - Cell (2021)
  7. A centric view of JAK/STAT5 in intestinal homeostasis, infection, and inflammation. - Marta Surbek;William Tse;Richard Moriggl;Xiaonan Han - Cytokine (2021)
  8. Transit-Amplifying Cells Coordinate Changes in Intestinal Epithelial Cell-Type Composition. - Laura E Sanman;Ina W Chen;Jake M Bieber;Veronica Steri;Coralie Trentesaux;Byron Hann;Ophir D Klein;Lani F Wu;Steven J Altschuler - Developmental cell (2021)
  9. JAK-STAT Pathway Inhibition Partially Restores Intestinal Homeostasis in Hdac1- and Hdac2-Intestinal Epithelial Cell-Deficient Mice. - Alexis Gonneaud;Naomie Turgeon;Francois-Michel Boisvert;Francois Boudreau;Claude Asselin - Cells (2021)
  10. Subversion of Niche-Signalling Pathways in Colorectal Cancer: What Makes and Breaks the Intestinal Stem Cell. - Nathalie Sphyris;Michael C Hodder;Owen J Sansom - Cancers (2021)

... (281 更多 篇文献)

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