The mechanisms that induce dedifferentiation to drive regeneration in the absence of stem cells (360G-Wellcome-210722_Z_18_Z)
Cell fate stability maintains functionality and counteracts malignancy in complex organisms. However, lack of exit gateways from the differentiated state impedes regeneration in mammals. Other animals regenerate by allowing differentiated cells to dedifferentiate, making progenitors to replace lost cells; however, the mechanisms that induce reprogramming are unknown. Based on our preliminary results we hypothesize that senescent cells can provide a signal instructing neighboring cells to exit the differentiated state and regain stemness under specific circumstances. Hence, this project's primary objective is to identify the nature of this signal and the context in which it operates. We will use Hydractinia, a highly regenerative invertebrate model animal in which reprogramming to pluripotency occurs naturally; Hydractinia is genetically tractable and optically translucent, uniquely allowing in vivo experiments. Our specific aims are (1) to characterize the transcriptome, epigenome and developmental potential of the animal's stem cells; (2) to identify the factors that cause differentiated cells to reprogram and become stem cells; (3) to dissect the transcriptional network acting during natural cellular reprogramming. This research will provide novel information on how cell fate is kept stable, and what are the mechanisms that allow non-malignant destabilization of cell fate to regain plasticity and contribute to regeneration.
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Grant Details
Amount Awarded | 473364 |
Applicant Surname | Frank |
Approval Committee | Science Interview Panel |
Award Date | 2018-04-10T00:00:00+00:00 |
Financial Year | 2017/18 |
Grant Programme: Title | Investigator Award in Science |
Internal ID | 210722/Z/18/Z |
Lead Applicant | Prof Uri Frank |
Partnership Name | SFI-HRB-Wellcome Trust partnership |
Partnership Value | 946728 |
Planned Dates: End Date | 2025-12-31T00:00:00+00:00 |
Planned Dates: Start Date | 2019-01-01T00:00:00+00:00 |
Recipient Org: Country | Ireland |
Region | Ireland |