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Single cell transcriptomics of human epidermis identifies basal stem cell transition states

Author

Listed:
  • Shuxiong Wang

    (University of California, Irvine
    University of California, Irvine
    University of California, Irvine)

  • Michael L. Drummond

    (University of California, Irvine)

  • Christian F. Guerrero-Juarez

    (University of California, Irvine
    University of California, Irvine
    University of California, Irvine)

  • Eric Tarapore

    (University of California, Irvine)

  • Adam L. MacLean

    (University of California, Irvine
    University of California, Irvine)

  • Adam R. Stabell

    (University of California, Irvine)

  • Stephanie C. Wu

    (University of California, Irvine)

  • Guadalupe Gutierrez

    (University of California, Irvine)

  • Bao T. That

    (University of California, Irvine)

  • Claudia A. Benavente

    (University of California, Irvine
    University of California, Irvine
    Chao Family Comprehensive Cancer Center, University of California, Irvine)

  • Qing Nie

    (University of California, Irvine
    University of California, Irvine
    University of California, Irvine
    Chao Family Comprehensive Cancer Center, University of California, Irvine)

  • Scott X. Atwood

    (University of California, Irvine
    University of California, Irvine
    Chao Family Comprehensive Cancer Center, University of California, Irvine
    University of California, Irvine)

Abstract

How stem cells give rise to epidermis is unclear despite the crucial role the epidermis plays in barrier and appendage formation. Here we use single cell-RNA sequencing to interrogate basal stem cell heterogeneity of human interfollicular epidermis and find four spatially distinct stem cell populations at the top and bottom of rete ridges and transitional positions between the basal and suprabasal epidermal layers. Cell-cell communication modeling suggests that basal cell populations serve as crucial signaling hubs to maintain epidermal communication. Combining pseudotime, RNA velocity, and cellular entropy analyses point to a hierarchical differentiation lineage supporting multi-stem cell interfollicular epidermal homeostasis models and suggest that transitional basal stem cells are stable states essential for proper stratification. Finally, alterations in differentially expressed transitional basal stem cell genes result in severe thinning of human skin equivalents, validating their essential role in epidermal homeostasis and reinforcing the critical nature of basal stem cell heterogeneity.

Suggested Citation

  • Shuxiong Wang & Michael L. Drummond & Christian F. Guerrero-Juarez & Eric Tarapore & Adam L. MacLean & Adam R. Stabell & Stephanie C. Wu & Guadalupe Gutierrez & Bao T. That & Claudia A. Benavente & Qi, 2020. "Single cell transcriptomics of human epidermis identifies basal stem cell transition states," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18075-7
    DOI: 10.1038/s41467-020-18075-7
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    Cited by:

    1. Sarah M. Lloyd & Daniel B. Leon & Mari O. Brady & Deborah Rodriguez & Madison P. McReynolds & Junghun Kweon & Amy E. Neely & Laura A. Blumensaadt & Patric J. Ho & Xiaomin Bao, 2022. "CDK9 activity switch associated with AFF1 and HEXIM1 controls differentiation initiation from epidermal progenitors," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Jiwoon Park & Eliah G. Overbey & S. Anand Narayanan & JangKeun Kim & Braden T. Tierney & Namita Damle & Deena Najjar & Krista A. Ryon & Jacqueline Proszynski & Ashley Kleinman & Jeremy Wain Hirschberg, 2024. "Spatial multi-omics of human skin reveals KRAS and inflammatory responses to spaceflight," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Daniel Haensel & Sadhana Gaddam & Nancy Y. Li & Fernanda Gonzalez & Tiffany Patel & Jeffrey M. Cloutier & Kavita Y. Sarin & Jean Y. Tang & Kerri E. Rieger & Sumaira Z. Aasi & Anthony E. Oro, 2022. "LY6D marks pre-existing resistant basosquamous tumor subpopulations," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Christian Reuter & Laura Hauf & Fabian Imdahl & Rituparno Sen & Ehsan Vafadarnejad & Philipp Fey & Tamara Finger & Nicola G. Jones & Heike Walles & Lars Barquist & Antoine-Emmanuel Saliba & Florian Gr, 2023. "Vector-borne Trypanosoma brucei parasites develop in artificial human skin and persist as skin tissue forms," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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