PUBLICATION
Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes
- Authors
- Lush, M.E., Tsai, Y.Y., Chen, S., Münch, D., Peloggia, J., Sandler, J.E., Piotrowski, T.
- ID
- ZDB-PUB-250715-13
- Date
- 2025
- Source
- Nature communications 16: 59135913 (Journal)
- Registered Authors
- Lush, Mark E., Piotrowski, Tatjana
- Keywords
- none
- Datasets
- GEO:GSE268255
- MeSH Terms
-
- Gene Expression Regulation, Developmental
- Cell Proliferation*/genetics
- Stem Cells*/cytology
- Stem Cells*/metabolism
- Cell Differentiation/genetics
- Animals
- Hair Cells, Auditory/cytology
- Hair Cells, Auditory/metabolism
- Zebrafish*/genetics
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Cyclin D*/genetics
- Cyclin D*/metabolism
- Cyclin D2/genetics
- Cyclin D2/metabolism
- PubMed
- 40659618 Full text @ Nat. Commun.
Citation
Lush, M.E., Tsai, Y.Y., Chen, S., Münch, D., Peloggia, J., Sandler, J.E., Piotrowski, T. (2025) Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes. Nature communications. 16:59135913.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping