Spatiotemporal regulation of multipotency during prostate development

Elisavet Tika, Marielle Ousset, Anne Dannau, C. Blanpain
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引用次数: 19

Abstract

ABSTRACT The prostate is formed by a branched glandular epithelium composed of basal cells (BCs) and luminal cells (LCs). Multipotent and unipotent stem cells (SCs) mediate the initial steps of prostate development whereas BCs and LCs are self-sustained in adult mice by unipotent lineage-restricted SCs. The spatiotemporal regulation of SC fate and the switch from multipotency to unipotency remain poorly characterised. Here, by combining lineage tracing, whole-tissue imaging, clonal analysis and proliferation kinetics, we uncover the cellular dynamics that orchestrate prostate postnatal development in mouse. We found that at an early stage of development multipotent basal SCs are located throughout the epithelium and are progressively restricted at the distal tip of the ducts, where, together with their progeny, they establish the different branches and the final structure of prostate. In contrast, pubertal development is mediated by unipotent lineage-restricted SCs. Our results uncover the spatiotemporal regulation of the switch from multipotency to unipotency during prostate development. Highlighted Article: A combination of lineage tracing and whole-mount imaging uncovers how the multipotency of basal stem cells is regulated during postnatal prostate development in mouse.
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前列腺发育过程中多能性的时空调控
前列腺是由基底细胞(BCs)和管腔细胞(LCs)组成的支状腺上皮形成的。多能性和单能性干细胞(SCs)介导前列腺发育的初始阶段,而BCs和LCs通过单能性谱系限制SCs在成年小鼠中自我维持。SC命运的时空调节和从多能性到单能性的转换仍然缺乏特征。在这里,通过结合谱系追踪、全组织成像、克隆分析和增殖动力学,我们揭示了协调小鼠前列腺出生后发育的细胞动力学。我们发现,在发育的早期阶段,多能基底SCs遍布上皮,并逐渐局限于导管的远端,在那里,它们与后代一起,建立了不同的分支和前列腺的最终结构。相反,青春期发育是由单能系限制性SCs介导的。我们的研究结果揭示了前列腺发育过程中从多能性到单能性转换的时空调节。谱系追踪和全贴装成像的结合揭示了小鼠出生后前列腺发育过程中基底干细胞的多能性是如何被调节的。
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