Lineage-specific CDK activity dynamics characterize early mammalian development
Summary: Cyclin-dependent kinases (CDKs) regulate proliferation dynamics and cell fate in response to extracellular inputs. It remains largely unknown how CDK activity fluctuates and influences cell commitment during early mammalian development. Here, we generated a mouse model expressing a CDK tran...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-04-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725003298 |
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| author | Bechara Saykali Andy D. Tran James A. Cornwell Matthew A. Caldwell Paniz Rezvan Sangsari Nicole Y. Morgan Michael J. Kruhlak Steven D. Cappell Sergio Ruiz |
| author_facet | Bechara Saykali Andy D. Tran James A. Cornwell Matthew A. Caldwell Paniz Rezvan Sangsari Nicole Y. Morgan Michael J. Kruhlak Steven D. Cappell Sergio Ruiz |
| author_sort | Bechara Saykali |
| collection | DOAJ |
| description | Summary: Cyclin-dependent kinases (CDKs) regulate proliferation dynamics and cell fate in response to extracellular inputs. It remains largely unknown how CDK activity fluctuates and influences cell commitment during early mammalian development. Here, we generated a mouse model expressing a CDK translocation reporter that enabled quantification of CDK activity in live single cells. By examining pre- and post-implantation mouse embryos at different stages, we observed a progressive decrease in CDK activity in cells from the trophectoderm (TE) prior to implantation. This drop seems to correlate with the available levels of ICM-derived FGF4 as CDK activity downregulation is rescued by exogenous FGF4. Furthermore, we showed that cell fate decisions in the pre-implantation embryo are not determined by the establishment of oscillatory CDK activity or overall changes in CDK activity. Finally, we uncovered the existence of conserved regulatory mechanisms in mammals by revealing lineage-specific regulation of CDK activity in TE-like human cells. |
| format | Article |
| id | doaj-art-6e475c16f77146c8ae19754922ecbdb1 |
| institution | DOAJ |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-6e475c16f77146c8ae19754922ecbdb12025-08-20T03:09:01ZengElsevierCell Reports2211-12472025-04-0144411555810.1016/j.celrep.2025.115558Lineage-specific CDK activity dynamics characterize early mammalian developmentBechara Saykali0Andy D. Tran1James A. Cornwell2Matthew A. Caldwell3Paniz Rezvan Sangsari4Nicole Y. Morgan5Michael J. Kruhlak6Steven D. Cappell7Sergio Ruiz8Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USALaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USALaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USALaboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USABiomedical Engineering and Physical Science Shared Resource, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USABiomedical Engineering and Physical Science Shared Resource, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USALaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USALaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USALaboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Corresponding authorSummary: Cyclin-dependent kinases (CDKs) regulate proliferation dynamics and cell fate in response to extracellular inputs. It remains largely unknown how CDK activity fluctuates and influences cell commitment during early mammalian development. Here, we generated a mouse model expressing a CDK translocation reporter that enabled quantification of CDK activity in live single cells. By examining pre- and post-implantation mouse embryos at different stages, we observed a progressive decrease in CDK activity in cells from the trophectoderm (TE) prior to implantation. This drop seems to correlate with the available levels of ICM-derived FGF4 as CDK activity downregulation is rescued by exogenous FGF4. Furthermore, we showed that cell fate decisions in the pre-implantation embryo are not determined by the establishment of oscillatory CDK activity or overall changes in CDK activity. Finally, we uncovered the existence of conserved regulatory mechanisms in mammals by revealing lineage-specific regulation of CDK activity in TE-like human cells.http://www.sciencedirect.com/science/article/pii/S2211124725003298CP: Developmental biology |
| spellingShingle | Bechara Saykali Andy D. Tran James A. Cornwell Matthew A. Caldwell Paniz Rezvan Sangsari Nicole Y. Morgan Michael J. Kruhlak Steven D. Cappell Sergio Ruiz Lineage-specific CDK activity dynamics characterize early mammalian development Cell Reports CP: Developmental biology |
| title | Lineage-specific CDK activity dynamics characterize early mammalian development |
| title_full | Lineage-specific CDK activity dynamics characterize early mammalian development |
| title_fullStr | Lineage-specific CDK activity dynamics characterize early mammalian development |
| title_full_unstemmed | Lineage-specific CDK activity dynamics characterize early mammalian development |
| title_short | Lineage-specific CDK activity dynamics characterize early mammalian development |
| title_sort | lineage specific cdk activity dynamics characterize early mammalian development |
| topic | CP: Developmental biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725003298 |
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