aPKCλ controls epidermal homeostasis and stem cell fate through regulation of division orientation.
aPKCλ controls epidermal homeostasis and stem cell fate through regulation of division orientation.
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DOI：
10.1083/jcb.201307001
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发表时间：
2013-09-16
期刊：
影响因子：
--
通讯作者：
Niessen CM
中科院分区：
文献类型：
--
作者：
Niessen MT;Scott J;Zielinski JG;Vorhagen S;Sotiropoulou PA;Blanpain C;Leitges M;Niessen CM
aPKCλ 的缺失会通过向不对称分裂的转变驱动细胞命运变化，从而破坏表皮稳态和凸起干细胞的维持。非典型蛋白激酶 C (aPKC) 是低等生物极性和细胞命运的关键调节因子。然而，哺乳动物 aPKC 是否在体内控制干细胞和命运尚不清楚。在这里，我们表明，自我更新的上皮、表皮中 aPKCλ 的丢失，会扰乱组织稳态、分化和干细胞动力学，从而导致该组织发生渐进性变化。伴随着静止毛囊干细胞的逐渐丧失和增殖祖细胞的暂时增加。谱系追踪分析表明，aPKCλ 的缺失改变了下部凸起/毛发生殖干细胞的命运。这最终导致增殖潜力丧失、干细胞耗竭、脱发和过早衰老。 aPKCλ 失活在不同区室中产生更多不对称分裂，包括凸起。因此，aPKCλ对于自我更新复层上皮细胞的稳态以及调节细胞命运、分化和表皮隆起干细胞的维持至关重要，可能是通过其平衡对称和不对称分裂的作用来实现的。
Loss of aPKCλ disrupts epidermal homeostasis and bulge stem cell maintenance by driving cell fate changes via a shift toward asymmetric division The atypical protein kinase C (aPKC) is a key regulator of polarity and cell fate in lower organisms. However, whether mammalian aPKCs control stem cells and fate in vivo is not known. Here we show that loss of aPKCλ in a self-renewing epithelium, the epidermis, disturbed tissue homeostasis, differentiation, and stem cell dynamics, causing progressive changes in this tissue. This was accompanied by a gradual loss of quiescent hair follicle bulge stem cells and a temporary increase in proliferating progenitors. Lineage tracing analysis showed that loss of aPKCλ altered the fate of lower bulge/hair germ stem cells. This ultimately led to loss of proliferative potential, stem cell exhaustion, alopecia, and premature aging. Inactivation of aPKCλ produced more asymmetric divisions in different compartments, including the bulge. Thus, aPKCλ is crucial for homeostasis of self-renewing stratifying epithelia, and for the regulation of cell fate, differentiation, and maintenance of epidermal bulge stem cells likely through its role in balancing symmetric and asymmetric division.
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影响因子：
9.2
作者：
Hao, Yi;Du, Quansheng;Chen, Xinyu;Zheng, Zhen;Balsbaugh, Jeremy L.;Maitra, Sushmit;Shabanowitz, Jeffrey;Hunt, Donald F.;Macara, Ian G.
通讯作者：
Macara, Ian G.
影响因子：
64.5
作者：
Hsu YC;Pasolli HA;Fuchs E
通讯作者：
Fuchs E
影响因子：
64.5
作者：
Horsley, Valerie;Aliprantis, Antonios O.;Fuchs, Elaine
通讯作者：
Fuchs, Elaine
影响因子：
1.2
作者：
Kovac, Judit;Oster, Henrik;Leitges, Michael
通讯作者：
Leitges, Michael
影响因子：
5.3
作者：
Baye, Lisa M.;Link, Brian A.
通讯作者：
Link, Brian A.