Department of Dermatology, Center for Molecular Medicine Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany.
J Cell Biol. 2013 Sep 16;202(6):887-900. doi: 10.1083/jcb.201307001. Epub 2013 Sep 9.
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.
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，自我更新上皮组织（表皮）中 aPKCλ 的缺失扰乱了组织稳态、分化和干细胞动力学，导致该组织的进行性变化。这伴随着静止的毛囊隆突干细胞逐渐丧失和增殖祖细胞的暂时增加。谱系追踪分析表明，aPKCλ 的缺失改变了较低隆突/毛囊生殖干细胞的命运。这最终导致增殖潜能丧失、干细胞衰竭、脱发和过早衰老。aPKCλ 的失活在不同隔室（包括隆突）中产生了更多的不对称分裂。因此，aPKCλ 对于自我更新的分层上皮组织的稳态，以及通过其在平衡对称和不对称分裂中的作用来调节细胞命运、分化和维持表皮隆突干细胞至关重要。
