Stem cell fate and plasticity in oesophageal wound healing. (360G-Wellcome-105942_Z_14_Z)
Wounds are thought to be repaired by a reserve stem cell population activated in response to injury. However, excisional wounding in mouse oesophagus has revealed a new model of tissue repair. The same progenitor population that maintains the tissue is able to switch its behaviour, tilting fate towards proliferation to generate the excess of cycling cells that will repair the tissue (Doupe, 2012). Progenitor cells are then able to regain stem cells properties to achieve a rapid and efficient hea ling response. This illustrates recent findings that show how cells committed to differentiation acquire stem cell-like behaviour upon damage in other epithelial tissues (van Es, 2012; Tata, 2013). Although this cellular plasticity is a strictly controlled and limited process, if inadequately activated in cells with pre-existing tumour initiating mutations it will have implications for cancer development. In the current proposal I set up to use my expertise in in vivo single cell lineage tracing to investigate short and long term changes in epithelial cell fate in response to injury, as well as the mesenchymal contribution to this process. Mechanistic insights will be gained by transcriptional network analysis and organotypic cultures specifically designed to recapitulate the epithelial wound response in vitro.
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Grant Details
Amount Awarded | 1073743 |
Applicant Surname | Alcolea |
Approval Committee | Sir Henry Dale Fellowship Interview Committee |
Award Date | 2014-10-29T00:00:00+00:00 |
Financial Year | 2014/15 |
Grant Programme: Title | Sir Henry Dale Fellowship |
Internal ID | 105942/Z/14/Z |
Lead Applicant | Dr Maria Alcolea |
Partnership Name | Royal Society/Wellcome Trust Sir Henry Dale Fellowship |
Partnership Value | 1073743 |
Planned Dates: End Date | 2025-01-04T00:00:00+00:00 |
Planned Dates: Start Date | 2016-01-05T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | East of England |
Sponsor(s) | Dr Bruce Ponder, Prof Austin Smith |