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Moore, J.L.* ; Bhaskar, D.* ; Gao, F.* ; Matte-Martone, C.* ; Du, S.* ; Lathrop, E.* ; Ganesan, S.* ; Shao, L.* ; Norris, R.* ; Campamà Sanz, N.* ; Annusver, K.* ; Kasper, M.* ; Cox, A.* ; Hendry, C.* ; Rieck, B. ; Krishnaswamy, S.* ; Greco, V.*

Cell cycle controls long-range calcium signaling in the regenerating epidermis.

J. Cell Biol. 222:30 (2023)
Publ. Version/Full Text DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Skin homeostasis is maintained by stem cells, which must communicate to balance their regenerative behaviors. Yet, how adult stem cells signal across regenerative tissue remains unknown due to challenges in studying signaling dynamics in live mice. We combined live imaging in the mouse basal stem cell layer with machine learning tools to analyze patterns of Ca2+ signaling. We show that basal cells display dynamic intercellular Ca2+ signaling among local neighborhoods. We find that these Ca2+ signals are coordinated across thousands of cells and that this coordination is an emergent property of the stem cell layer. We demonstrate that G2 cells are required to initiate normal levels of Ca2+ signaling, while connexin43 connects basal cells to orchestrate tissue-wide coordination of Ca2+ signaling. Lastly, we find that Ca2+ signaling drives cell cycle progression, revealing a communication feedback loop. This work provides resolution into how stem cells at different cell cycle stages coordinate tissue-wide signaling during epidermal regeneration.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Transgenic Mice; Ca2+ Response; Expression; Differentiation; Activation; Keratinocytes; Pathway; Proliferation; Visualization; Specificity
ISSN (print) / ISBN 0021-9525
e-ISSN 1540-8140
Journal Journal of Cell Biology, The
Quellenangaben Volume: 222, Issue: 7, Pages: , Article Number: 30 Supplement: ,
Publisher Rockefeller University Press
Publishing Place 950 Third Ave, 2nd Flr, New York, Ny 10022 Usa
Reviewing status Peer reviewed
Institute(s) Helmholtz Pioneer Campus (HPC)
Grants
Chan Zuckerberg Foundation
Sloan Fellowship
National Science Foundation Career Grant
Yale-Boehringer Ingelheim Biomedical Data Science Fellowship
NIH
Lo Graduate Fellowship for Excellence in Stem Cell Research
National Institute On Aging of the National Institutes of Health
National Institute Of Arthritis And Musculoskeletal And Skin Diseases of the NIH
Howard Hughes Medical Institute Scholar award