Atypical PKC-iota Controls Stem Cell Expansion via Regulation of the Notch Pathway.
Atypical PKC-iota Controls Stem Cell Expansion via Regulation of the Notch Pathway.
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DOI：
10.1016/j.stemcr.2015.09.021
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发表时间：
2015-11-10
影响因子：
5.9
通讯作者：
Mariani FV
中科院分区：
文献类型：
--
作者：
Mah IK;Soloff R;Hedrick SM;Mariani FV
可用的干细胞/祖细胞的数量可以深刻地影响组织的动态平衡和对损伤或疾病的反应。在这里，我们认为一个非典型的PKC，PrkCi，是通过调节Notch调控从扩增到分化/维持阶段的关键角色，从而将极性途径与干细胞自我更新的控制联系在一起。已知Prkci影响无脊椎动物的对称细胞分裂；然而，在哺乳动物中还没有出现明确的作用。使用遗传学方法，我们发现Prkci的丢失导致各种干/祖细胞数量的显著增加。使用的机制可能涉及Numb的失活和对称局部化，导致NOTCH1及其下游效应器的激活。抑制非典型的PKC可能有助于促进多能干细胞、多能干细胞的产生，甚至可能通过促进干细胞/祖细胞的命运来促进原始生殖细胞的产生。PRKCi是一种极性蛋白质，通过Notch依赖的途径调节各种干/祖细胞的扩张。因此，PRKCi在极性和干细胞自我更新之间起到了连接作用。抑制APKC的自我更新通常对扩大祖细胞种群有用。Mariani及其同事证明，PRKCi是一种控制细胞极性的非典型PKC，通过Notch途径调节各种干/祖细胞的扩张。因此，PRKCi将极性的控制与干细胞自我更新的途径联系起来。抑制aPKC可能有助于促进某些祖细胞/干细胞群体的产生。
The number of stem/progenitor cells available can profoundly impact tissue homeostasis and the response to injury or disease. Here, we propose that an atypical PKC, Prkci, is a key player in regulating the switch from an expansion to a differentiation/maintenance phase via regulation of Notch, thus linking the polarity pathway with the control of stem cell self-renewal. Prkci is known to influence symmetric cell division in invertebrates; however a definitive role in mammals has not yet emerged. Using a genetic approach, we find that loss of Prkci results in a marked increase in the number of various stem/progenitor cells. The mechanism used likely involves inactivation and symmetric localization of NUMB, leading to the activation of NOTCH1 and its downstream effectors. Inhibition of atypical PKCs may be useful for boosting the production of pluripotent stem cells, multipotent stem cells, or possibly even primordial germ cells by promoting the stem cell/progenitor fate. PRKCi, a polarity protein, regulates expansion of various stem/progenitor cells PRKCi acts in this capacity via a Notch-dependent pathway Thus, PRKCi acts as a link between polarity and stem cell self-renewal Inhibition of aPKCs may be generally useful for expanding progenitor populations Mariani and colleagues show that PRKCi, an atypical PKC that controls cell polarity, regulates the expansion of various stem/progenitor cells via the Notch pathway. Thus, PRKCi links the control of polarity with a pathway for stem cell self-renewal. Inhibition of aPKCs may be useful for boosting the production of certain progenitor/stem cell populations.