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肾祖细胞的定向决定是一个受细胞迁移影响的随机过程。

Nephron progenitor commitment is a stochastic process influenced by cell migration.

机构信息

Murdoch Children's Research Institute, Parkville, Australia.

School of Biosciences, University of Melbourne, Melbourne, Australia.

出版信息

Elife. 2019 Jan 24;8:e41156. doi: 10.7554/eLife.41156.

DOI:10.7554/eLife.41156
PMID:30676318
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6363379/
Abstract

Progenitor self-renewal and differentiation is often regulated by spatially restricted cues within a tissue microenvironment. Here, we examine how progenitor cell migration impacts regionally induced commitment within the nephrogenic niche in mice. We identify a subset of cells that express , an early marker of nephron commitment, but migrate back into the progenitor population where they accumulate over time. Single cell RNA-seq and computational modelling of returning cells reveals that nephron progenitors can traverse the transcriptional hierarchy between self-renewal and commitment in either direction. This plasticity may enable robust regulation of nephrogenesis as niches remodel and grow during organogenesis.

摘要

祖细胞的自我更新和分化通常受到组织微环境中空间限制信号的调控。在这里,我们研究了祖细胞迁移如何影响小鼠肾发生龛内局部诱导的祖细胞向特定细胞分化。我们发现了一小部分表达早期肾单位分化标志物的细胞,但它们会迁移回祖细胞群体中,并随着时间的推移逐渐积累。对返回细胞的单细胞 RNA 测序和计算模型分析表明,肾祖细胞可以在自我更新和分化之间的转录层次结构中双向穿梭。这种可塑性可能使肾发生在器官发生过程中龛重塑和生长时能够得到稳健的调控。

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1
Nephron progenitor commitment is a stochastic process influenced by cell migration.肾祖细胞的定向决定是一个受细胞迁移影响的随机过程。
Elife. 2019 Jan 24;8:e41156. doi: 10.7554/eLife.41156.
2
Wnt11 directs nephron progenitor polarity and motile behavior ultimately determining nephron endowment.Wnt11 指导肾祖细胞的极性和运动行为,最终决定肾单位的数量。
Elife. 2018 Dec 5;7:e40392. doi: 10.7554/eLife.40392.
3
p53 Enables metabolic fitness and self-renewal of nephron progenitor cells.p53 使肾祖细胞能够适应代谢并实现自我更新。
Development. 2015 Apr 1;142(7):1228-41. doi: 10.1242/dev.111617.
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Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation.动态 MAPK/ERK 活性通过小生境调节维持肾祖细胞,并为分化前体细胞做好准备。
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Differential regulation of mouse and human nephron progenitors by the Six family of transcriptional regulators.转录调节因子Six家族对小鼠和人类肾单位祖细胞的差异调节。
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Nephron progenitor cell commitment: Striking the right balance.肾祖细胞的定向分化:把握恰当的平衡。
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Mdm2 is required for maintenance of the nephrogenic niche.Mdm2 对于肾源龛的维持是必需的。
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Osr1 acts downstream of and interacts synergistically with Six2 to maintain nephron progenitor cells during kidney organogenesis.Osr1 在肾脏器官发生过程中,作用于 Six2 的下游并与其协同作用,以维持肾祖细胞。
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Nephron progenitor fate is modulated by angiotensin type 1 receptor signaling in human kidney organoids.肾单位祖细胞命运受人类肾脏类器官中血管紧张素1型受体信号传导的调控。

本文引用的文献

1
Progressive Recruitment of Mesenchymal Progenitors Reveals a Time-Dependent Process of Cell Fate Acquisition in Mouse and Human Nephrogenesis.渐进式招募间充质祖细胞揭示了小鼠和人肾发生中细胞命运获得的时间依赖性过程。
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Disparate levels of beta-catenin activity determine nephron progenitor cell fate.β-连环蛋白活性水平的差异决定了肾单位祖细胞的命运。
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Nephron progenitors rhythmically alternate between renewal and differentiation phases that synchronize with kidney branching morphogenesis.肾单位祖细胞在与肾脏分支形态发生同步的更新和分化阶段之间有节奏地交替。
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整合不同条件、技术和物种的单细胞转录组数据。
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Conserved and Divergent Features of Human and Mouse Kidney Organogenesis.人类和小鼠肾脏发生的保守和分化特征。
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A step-by-step workflow for low-level analysis of single-cell RNA-seq data with Bioconductor.使用Bioconductor进行单细胞RNA测序数据低级分析的逐步工作流程。
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