title: aPKCλ controls epidermal homeostasis and stem cell fate through regulation of division orientation.
abstract: 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.
authors.affiliation: 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.
authors.forename: Michaela T
authors.initials: MT
authors.lastname: Niessen
authors.forename: Jeanie
authors.initials: J
authors.lastname: Scott
authors.forename: Julia G
authors.initials: JG
authors.lastname: Zielinski
authors.forename: Susanne
authors.initials: S
authors.lastname: Vorhagen
authors.forename: Panagiota A
authors.initials: PA
authors.lastname: Sotiropoulou
authors.forename: Cédric
authors.initials: C
authors.lastname: Blanpain
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
authors.forename: Carien M
authors.initials: CM
authors.lastname: Niessen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000502:physiology*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011493:Protein Kinase C / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D000099293:Protein Kinase C-lambda
chemical_list: D007527:Isoenzymes; D011493:Protein Kinase C; D012333:RNA, Messenger; D000099293:Protein Kinase C-lambda
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