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Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes

Author

Listed:
  • Mark E. Lush

    (Stowers Institute for Medical Research)

  • Ya-Yin Tsai

    (Stowers Institute for Medical Research)

  • Shiyuan Chen

    (Stowers Institute for Medical Research)

  • Daniela Münch

    (Stowers Institute for Medical Research)

  • Julia Peloggia

    (Stowers Institute for Medical Research
    Los Angeles (UCLA))

  • Jeremy E. Sandler

    (Stowers Institute for Medical Research)

  • Tatjana Piotrowski

    (Stowers Institute for Medical Research)

Abstract

Regeneration and homeostatic turnover of solid tissues depend on the proliferation of symmetrically dividing adult stem cells, which either remain stem cells or differentiate based on their niche position. Here we demonstrate that in zebrafish lateral line sensory organs, stem and progenitor cell proliferation are independently regulated by two cyclinD genes. Loss of ccnd2a impairs stem cell proliferation during development, while loss of ccndx disrupts hair cell progenitor proliferation but allows normal differentiation. Notably, ccnd2a can functionally replace ccndx, indicating that the respective effects of these Cyclins on proliferation are due to cell type-specific expression. However, even though hair cell progenitors differentiate normally in ccndx mutants, they are mispolarized due to hes2 and Emx2 downregulation. Thus, regulated proliferation ensures that equal numbers of hair cells are polarized in opposite directions. Our study reveals cell type-specific roles for cyclinD genes in regulating the different populations of symmetrically dividing cells governing organ development and regeneration, with implications for regenerative medicine and disease.

Suggested Citation

  • Mark E. Lush & Ya-Yin Tsai & Shiyuan Chen & Daniela Münch & Julia Peloggia & Jeremy E. Sandler & Tatjana Piotrowski, 2025. "Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60251-0
    DOI: 10.1038/s41467-025-60251-0
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    References listed on IDEAS

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    1. Andrew S. Yoo & Brett T. Staahl & Lei Chen & Gerald R. Crabtree, 2009. "MicroRNA-mediated switching of chromatin-remodelling complexes in neural development," Nature, Nature, vol. 460(7255), pages 642-646, July.
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    3. Joaquin Navajas Acedo & Matthew G. Voas & Richard Alexander & Thomas Woolley & Jay R. Unruh & Hua Li & Cecilia Moens & Tatjana Piotrowski, 2019. "PCP and Wnt pathway components act in parallel during zebrafish mechanosensory hair cell orientation," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
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