Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes
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 progenito...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60251-0 |
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| author | Mark E. Lush Ya-Yin Tsai Shiyuan Chen Daniela Münch Julia Peloggia Jeremy E. Sandler Tatjana Piotrowski |
| author_facet | Mark E. Lush Ya-Yin Tsai Shiyuan Chen Daniela Münch Julia Peloggia Jeremy E. Sandler Tatjana Piotrowski |
| author_sort | Mark E. Lush |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-aabe9388eff64a82ae6f2b9168b8ed1e |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-aabe9388eff64a82ae6f2b9168b8ed1e2025-08-20T03:43:14ZengNature PortfolioNature Communications2041-17232025-07-0116111910.1038/s41467-025-60251-0Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genesMark E. Lush0Ya-Yin Tsai1Shiyuan Chen2Daniela Münch3Julia Peloggia4Jeremy E. Sandler5Tatjana Piotrowski6Stowers Institute for Medical ResearchStowers Institute for Medical ResearchStowers Institute for Medical ResearchStowers Institute for Medical ResearchStowers Institute for Medical ResearchStowers Institute for Medical ResearchStowers Institute for Medical ResearchAbstract 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.https://doi.org/10.1038/s41467-025-60251-0 |
| spellingShingle | Mark E. Lush Ya-Yin Tsai Shiyuan Chen Daniela Münch Julia Peloggia Jeremy E. Sandler Tatjana Piotrowski Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes Nature Communications |
| title | Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes |
| title_full | Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes |
| title_fullStr | Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes |
| title_full_unstemmed | Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes |
| title_short | Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes |
| title_sort | stem and progenitor cell proliferation are independently regulated by cell type specific cyclind genes |
| url | https://doi.org/10.1038/s41467-025-60251-0 |
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