A Transit-amplifying Progenitor with Biphasic Behavior Contributes to Epidermal Renewal

Overview

Journal Development

Specialty Biology

Date 2024 Jun 27

PMID 38934416

Authors

Sangeeta Ghuwalewala

Kevin Jiang

Sara Ragi

David Shalloway

Tudorita Tumbar

Affiliations

Soon will be listed here.

Abstract

Transit-amplifying (TA) cells are progenitors that undergo an amplification phase followed by transition into an extinction phase. A long postulated epidermal TA progenitor with biphasic behavior has not yet been experimentally observed in vivo. Here, we identify such a TA population using clonal analysis of Aspm-CreER genetic cell-marking in mice, which uncovers contribution to both homeostasis and injury repair of adult skin. This TA population is more frequently dividing than a Dlx1-CreER-marked long-term self-renewing (e.g. stem cell) population. Newly developed generalized birth-death modeling of long-term lineage tracing data shows that both TA progenitors and stem cells display neutral competition, but only the stem cells display neutral drift. The quantitative evolution of a nascent TA cell and its direct descendants shows that TA progenitors indeed amplify the basal layer before transition and that the homeostatic TA population is mostly in extinction phase. This model will be broadly useful for analyzing progenitors whose behavior changes with their clone age. This work identifies a long-missing class of non-self-renewing biphasic epidermal TA progenitors and has broad implications for understanding tissue renewal mechanisms.

References

Gomez C, Chua W, Miremadi A, Quist S, Headon D, Watt F . The interfollicular epidermis of adult mouse tail comprises two distinct cell lineages that are differentially regulated by Wnt, Edaradd, and Lrig1. Stem Cell Reports. 2013; 1(1):19-27. PMC: 3757744. DOI: 10.1016/j.stemcr.2013.04.001. View

Potten C, Loeffler M . Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development. 1990; 110(4):1001-20. DOI: 10.1242/dev.110.4.1001. View

Furuyama K, Kawaguchi Y, Akiyama H, Horiguchi M, Kodama S, Kuhara T . Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine. Nat Genet. 2010; 43(1):34-41. DOI: 10.1038/ng.722. View

Blanpain C, Simons B . Unravelling stem cell dynamics by lineage tracing. Nat Rev Mol Cell Biol. 2013; 14(8):489-502. DOI: 10.1038/nrm3625. View

Hsu Y, Fuchs E . Building and Maintaining the Skin. Cold Spring Harb Perspect Biol. 2021; 14(7). PMC: 8977401. DOI: 10.1101/cshperspect.a040840. View

Rompolas P, Mesa K, Kawaguchi K, Park S, Gonzalez D, Brown S . Spatiotemporal coordination of stem cell commitment during epidermal homeostasis. Science. 2016; 352(6292):1471-4. PMC: 4958018. DOI: 10.1126/science.aaf7012. View

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

Tian H, Biehs B, Warming S, Leong K, Rangell L, Klein O . A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature. 2011; 478(7368):255-9. PMC: 4251967. DOI: 10.1038/nature10408. View

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

10.

Pei W, Shang F, Wang X, Fanti A, Greco A, Busch K . Resolving Fates and Single-Cell Transcriptomes of Hematopoietic Stem Cell Clones by PolyloxExpress Barcoding. Cell Stem Cell. 2020; 27(3):383-395.e8. DOI: 10.1016/j.stem.2020.07.018. View

11.

Haensel D, Jin S, Sun P, Cinco R, Dragan M, Nguyen Q . Defining Epidermal Basal Cell States during Skin Homeostasis and Wound Healing Using Single-Cell Transcriptomics. Cell Rep. 2020; 30(11):3932-3947.e6. PMC: 7218802. DOI: 10.1016/j.celrep.2020.02.091. View

12.

Kang S, Long K, Wang S, Sada A, Tumbar T . Histone H3 K4/9/27 Trimethylation Levels Affect Wound Healing and Stem Cell Dynamics in Adult Skin. Stem Cell Reports. 2019; 14(1):34-48. PMC: 6962642. DOI: 10.1016/j.stemcr.2019.11.007. View

13.

Madisen L, Zwingman T, Sunkin S, Oh S, Zariwala H, Gu H . A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci. 2009; 13(1):133-40. PMC: 2840225. DOI: 10.1038/nn.2467. View

14.

Chen E, Tan C, Kou Y, Duan Q, Wang Z, Meirelles G . Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics. 2013; 14:128. PMC: 3637064. DOI: 10.1186/1471-2105-14-128. View

15.

Enzo E, Secone Seconetti A, Forcato M, Tenedini E, Polito M, Sala I . Single-keratinocyte transcriptomic analyses identify different clonal types and proliferative potential mediated by FOXM1 in human epidermal stem cells. Nat Commun. 2021; 12(1):2505. PMC: 8097075. DOI: 10.1038/s41467-021-22779-9. View

16.

Potten C . The epidermal proliferative unit: the possible role of the central basal cell. Cell Tissue Kinet. 1974; 7(1):77-88. DOI: 10.1111/j.1365-2184.1974.tb00401.x. View

17.

Ghuwalewala S, Lee S, Jiang K, Baidya J, Chovatiya G, Kaur P . Binary organization of epidermal basal domains highlights robustness to environmental exposure. EMBO J. 2022; 41(18):e110488. PMC: 9475544. DOI: 10.15252/embj.2021110488. View

18.

Tumbar T, Guasch G, Greco V, Blanpain C, Lowry W, Rendl M . Defining the epithelial stem cell niche in skin. Science. 2003; 303(5656):359-63. PMC: 2405920. DOI: 10.1126/science.1092436. View

19.

Potten C, Wichmann H, Loeffler M, Dobek K, Major D . Evidence for discrete cell kinetic subpopulations in mouse epidermis based on mathematical analysis. Cell Tissue Kinet. 1982; 15(3):305-29. DOI: 10.1111/j.1365-2184.1982.tb01050.x. View

20.

Bryder D, Rossi D, Weissman I . Hematopoietic stem cells: the paradigmatic tissue-specific stem cell. Am J Pathol. 2006; 169(2):338-46. PMC: 1698791. DOI: 10.2353/ajpath.2006.060312. View