Multipotent and unipotent progenitors contribute to prostate postnatal development
Multipotent and unipotent progenitors contribute to prostate postnatal development
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DOI：
10.1038/ncb2600
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发表时间：
2012-11-01
影响因子：
21.3
通讯作者：
Blanpain, Cedric
中科院分区：
文献类型：
--
作者：
Ousset, Marielle;Van Keymeulen, Alexandra;Blanpain, Cedric
前列腺是一种腺上皮，由基细胞、腔细胞和神经内分泌细胞组成，在胚胎发育过程中起源于泌尿生殖窦。出生后，前列腺一直发育到青春期结束。在这里，我们使用可诱导的小鼠遗传谱系追踪实验来研究控制前列腺出生后发育的细胞层次。我们发现，前列腺出生后的发育是由分化为基细胞、腔细胞和神经内分泌细胞的基底多能干细胞以及单能的基础和腔祖细胞介导的。对基底细胞的克隆分析表明，存在双能和单能的基底祖细胞，以及已经致力于腔系的基底细胞，中间细胞共同表达与这一承诺步骤相关的基础和腔标记。在前列腺生后发育过程中，多能基祖细胞的存在与介导成人前列腺再生的单能基干细胞池和腔干细胞池形成了鲜明的对比。我们的结果揭示了在前列腺发育过程中起作用的细胞层次结构，并将有助于确定细胞起源和前列腺癌发生的机制。
The prostate is a glandular epithelium composed of basal, luminal and neuroendocrine cells that originate from the urogenital sinus during embryonic development. After birth, the prostate keeps developing until the end of puberty. Here, we used inducible genetic lineage tracing experiments in mice to investigate the cellular hierarchy that governs prostate postnatal development. We found that prostate postnatal development is mediated by basal multipotent stem cells that differentiate into basal, luminal and neuroendocrine cells, as well as by unipotent basal and luminal progenitors. Clonal analysis of basal cells revealed the existence of bipotent and unipotent basal progenitors as well as basal cells already committed to the luminal lineage with intermediate cells co-expressing basal and luminal markers associated with this commitment step. The existence of multipotent basal progenitors during prostate postnatal development contrasts with the distinct pools of unipotent basal and luminal stem cells that mediate adult prostate regeneration. Our results uncover the cellular hierarchy acting during prostate development and will be instrumental in defining the cellular origin and the mechanisms underlying prostate cancer initiation.