Cell and molecular transitions during efficient dedifferentiation.
John Me Nichols, Vlatka Antolović, Jacob D Reich, Sophie Brameyer, Peggy Paschke, Jonathan R Chubb
Author Information
John Me Nichols: MRC Laboratory for Molecular Cell Biology and Department of Cell and Developmental Biology, University College London, London, United Kingdom. ORCID
Vlatka Antolović: MRC Laboratory for Molecular Cell Biology and Department of Cell and Developmental Biology, University College London, London, United Kingdom. ORCID
Jacob D Reich: MRC Laboratory for Molecular Cell Biology and Department of Cell and Developmental Biology, University College London, London, United Kingdom.
Sophie Brameyer: Ludwig-Maximilians-University Munich, Martinsried, Germany. ORCID
Peggy Paschke: CRUK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, Glasgow, United Kingdom.
Jonathan R Chubb: MRC Laboratory for Molecular Cell Biology and Department of Cell and Developmental Biology, University College London, London, United Kingdom. ORCID
Dedifferentiation is a critical response to tissue damage, yet is not well understood, even at a basic phenomenological level. Developing cells undergo highly efficient dedifferentiation, completed by most cells within 24 hr. We use this rapid response to investigate the control features of dedifferentiation, combining single cell imaging with high temporal resolution transcriptomics. Gene expression during dedifferentiation was predominantly a simple reversal of developmental changes, with expression changes not following this pattern primarily associated with ribosome biogenesis. Mutation of genes induced early in dedifferentiation did not strongly perturb the reversal of development. This apparent robustness may arise from adaptability of cells: the relative temporal ordering of cell and molecular events was not absolute, suggesting cell programmes reach the same end using different mechanisms. In addition, although cells start from different fates, they rapidly converged on a single expression trajectory. These regulatory features may contribute to dedifferentiation responses during regeneration.
