MaRMN Special Seminar: Mekayla Storer, Hospital for Sick Children, Toronto
|Starts:||11:30 31 Jan 2020|
|Ends:||12:30 31 Jan 2020|
|What is it:||Seminar|
|Organiser:||Faculty of Biology, Medicine and Health|
|Who is it for:||University staff, Adults, Current University students|
Mekayla A. Storer, Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Canada
Regeneration of appendages is relatively common among invertebrates. In mammals, however, multi-tissue regeneration is largely restricted to the distal portion of the digit tip, and involves the formation of a blastema, a heterogeneous, transiently proliferating cell mass that forms between the injured bone and the newly formed epidermis.
While the blastema is becoming increasingly well understood in amphibians, in mammals, we do not know where most mesenchymal blastema cells come from, what cellular state they adopt as blastema cells and/or whether they are flexible in terms of the mesenchymal lineages they generate. Here, we show that Pdgfra-expressing mesenchymal cells in uninjured adult murine digits establish the regenerative blastema and are essential for successful regeneration.
Single cell profiling demonstrates that the mesenchymal blastema cells are distinct from both uninjured digit and embryonic limb/digit Pdgfra-positive cells. This unique state is environmentally determined, since dermal fibroblasts transplanted into the regenerating digit will acquire a blastema phenotype and contribute to bone regeneration. Similarly, lineage tracing and single cell profiling show that endogenous bone-associated mesenchymal cells also acquire the blastema transcriptional identity and contribute to dermis and bone regeneration.
Thus, mammalian digit tip regeneration occurs via a distinct adult mechanism where the regenerative environment promotes acquisition of a unique blastema state that allows cells to contribute broadly to mesenchymal tissue repair and regeneration. Therefore, if we can understand the growth factors and signalling cascades that regulate blastema formation and cellular plasticity, this might tell us why regeneration fails in most mammalian situations and provide insights into therapeutic strategies for reversing this failure.
Organisation: Hospital for Sick Children, Toronto, Canada
Travel and Contact Information
Michael Smith lecture theatre
Michael Smith Building