APKCλ Controls Epidermal Homeostasis and Stem Cell Fate Through Regulation of Division Orientation

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2013 Sep 11

PMID 24019538

Citations 49

Authors

Michaela T Niessen

Jeanie Scott

Julia G Zielinski

Susanne Vorhagen

Panagiota A Sotiropoulou

Cedric Blanpain

Michael Leitges

Carien M Niessen

Affiliations

Soon will be listed here.

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.

Citing Articles

Rare variants in cause Van der Woude syndrome and other features of peridermopathy.

Robinson K, Robinson K, Singh S, Walkup R, Fawwal D, Adeyemo W medRxiv. 2025; .

PMID: 39867391 PMC: 11759255. DOI: 10.1101/2025.01.17.25320742.

The role of cell-cell and cell-matrix junctional complexes in sebaceous gland homeostasis and differentiation.

Yaba A, Thalheim T, Schneider M Cell Commun Signal. 2024; 22(1):445.

PMID: 39313816 PMC: 11421122. DOI: 10.1186/s12964-024-01835-z.

Polarity signaling balances epithelial contractility and mechanical resistance.

Rubsam M, Pullen R, Tellkamp F, Bianco A, Peskoller M, Bloch W Sci Rep. 2023; 13(1):7743.

PMID: 37173371 PMC: 10182030. DOI: 10.1038/s41598-023-33485-5.

Distinct types of stem cell divisions determine organ regeneration and aging in hair follicles.

Matsumura H, Liu N, Nanba D, Ichinose S, Takada A, Kurata S Nat Aging. 2023; 1(2):190-204.

PMID: 37118636 DOI: 10.1038/s43587-021-00033-7.

Polarity in skin development and cancer.

Prado-Mantilla A, Lechler T Curr Top Dev Biol. 2023; 154:317-336.

PMID: 37100522 PMC: 10288382. DOI: 10.1016/bs.ctdb.2023.02.003.

References

Zhang Y, Cheong J, Ciapurin N, McDermitt D, Tumbar T . Distinct self-renewal and differentiation phases in the niche of infrequently dividing hair follicle stem cells. Cell Stem Cell. 2009; 5(3):267-78. PMC: 2756832. DOI: 10.1016/j.stem.2009.06.004. View

Goulas S, Conder R, Knoblich J . The Par complex and integrins direct asymmetric cell division in adult intestinal stem cells. Cell Stem Cell. 2012; 11(4):529-40. PMC: 3465556. DOI: 10.1016/j.stem.2012.06.017. View

Encinas J, Michurina T, Peunova N, Park J, Tordo J, Peterson D . Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell. 2011; 8(5):566-79. PMC: 3286186. DOI: 10.1016/j.stem.2011.03.010. View

Poulson N, Lechler T . Asymmetric cell divisions in the epidermis. Int Rev Cell Mol Biol. 2012; 295:199-232. PMC: 3549531. DOI: 10.1016/B978-0-12-394306-4.00012-5. View

Jaks V, Kasper M, Toftgard R . The hair follicle-a stem cell zoo. Exp Cell Res. 2010; 316(8):1422-8. DOI: 10.1016/j.yexcr.2010.03.014. View

Schweizer J, Langbein L, Rogers M, Winter H . Hair follicle-specific keratins and their diseases. Exp Cell Res. 2007; 313(10):2010-20. DOI: 10.1016/j.yexcr.2007.02.032. View

Miyata T, Kawaguchi D, Kawaguchi A, Gotoh Y . Mechanisms that regulate the number of neurons during mouse neocortical development. Curr Opin Neurobiol. 2010; 20(1):22-8. DOI: 10.1016/j.conb.2010.01.001. View

Helfrich I, Schmitz A, Zigrino P, Michels C, Haase I, Le Bivic A . Role of aPKC isoforms and their binding partners Par3 and Par6 in epidermal barrier formation. J Invest Dermatol. 2006; 127(4):782-91. DOI: 10.1038/sj.jid.5700621. View

Horsley V, Aliprantis A, Polak L, Glimcher L, Fuchs E . NFATc1 balances quiescence and proliferation of skin stem cells. Cell. 2008; 132(2):299-310. PMC: 2546702. DOI: 10.1016/j.cell.2007.11.047. View

10.

Blanpain C, Fuchs E . Epidermal homeostasis: a balancing act of stem cells in the skin. Nat Rev Mol Cell Biol. 2009; 10(3):207-17. PMC: 2760218. DOI: 10.1038/nrm2636. View

11.

Murray N, Weems J, Braun U, Leitges M, Fields A . Protein kinase C betaII and PKCiota/lambda: collaborating partners in colon cancer promotion and progression. Cancer Res. 2009; 69(2):656-62. PMC: 2688739. DOI: 10.1158/0008-5472.CAN-08-3001. View

12.

Mascre G, Dekoninck S, Drogat B, Youssef K, Brohee S, Sotiropoulou P . Distinct contribution of stem and progenitor cells to epidermal maintenance. Nature. 2012; 489(7415):257-62. DOI: 10.1038/nature11393. View

13.

Bandyopadhyay G, Standaert M, Sajan M, Kanoh Y, Miura A, Braun U . Protein kinase C-lambda knockout in embryonic stem cells and adipocytes impairs insulin-stimulated glucose transport. Mol Endocrinol. 2003; 18(2):373-83. DOI: 10.1210/me.2003-0087. View

14.

St Johnston D, Ahringer J . Cell polarity in eggs and epithelia: parallels and diversity. Cell. 2010; 141(5):757-74. DOI: 10.1016/j.cell.2010.05.011. View

15.

Fields A, Frederick L, Regala R . Targeting the oncogenic protein kinase Ciota signalling pathway for the treatment of cancer. Biochem Soc Trans. 2007; 35(Pt 5):996-1000. DOI: 10.1042/BST0350996. View

16.

Tunggal J, Helfrich I, Schmitz A, Schwarz H, Gunzel D, Fromm M . E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions. EMBO J. 2005; 24(6):1146-56. PMC: 556407. DOI: 10.1038/sj.emboj.7600605. View

17.

Snippert H, van der Flier L, Sato T, van Es J, van den Born M, Kroon-Veenboer C . Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell. 2010; 143(1):134-44. DOI: 10.1016/j.cell.2010.09.016. View

18.

Jaks V, Barker N, Kasper M, van Es J, Snippert H, Clevers H . Lgr5 marks cycling, yet long-lived, hair follicle stem cells. Nat Genet. 2008; 40(11):1291-9. DOI: 10.1038/ng.239. View

19.

Smart I . Variation in the plane of cell cleavage during the process of stratification in the mouse epidermis. Br J Dermatol. 1970; 82(3):276-82. DOI: 10.1111/j.1365-2133.1970.tb12437.x. View

20.

Williams S, Beronja S, Pasolli H, Fuchs E . Asymmetric cell divisions promote Notch-dependent epidermal differentiation. Nature. 2011; 470(7334):353-8. PMC: 3077085. DOI: 10.1038/nature09793. View