Identification of proteins involved in pancreatic endocrine progenitor cell development.

Abstract

Pancreatic endocrine progenitor (PEP) cells can serve as an additional pool of cells for the Edmonton protocol (transportation of islets of Langerhans), a form of treatment for Type 1 Diabetes. This treatment is, however, limited by the shortage of donors. PEP cells can be efficiently generated in vitro from stem cells and following transplantation mature into functional beta-cells. Additionally, unlike stem cells, PEP cells do not carry the risk of teratoma formation. However, currently available differentiation protocols still yield a mixed population of cells, therefore PEP cells have to be isolated based on their expression profile. PEP cells are currently identified based on expression of transcription factors (TFs). Although, TFs are nuclear proteins, therefore, isolation of intact PEP cells is not possible. In order to apply antibody-based cell sorting for PEP cells isolation cell membrane marker proteins specific to those cells need to be identified. Here a list of novel putative markers for PEP cells has been generated. This was achieved by transcriptomic and proteomic analysis of PEP cells generated from induced pluripotent stem cells (iPSCs). Additionally, data mining analysis applied here revealed signalling process previously not strongly associated with pancreatic development. Moreover, recently developed pancreatic mesenchymal stem cells (MSCs) were also tested for their potential to differentiate into PEP cells. Those cells were subjected to differentiation with a small compound Isx-9 and a stepwise protocol with conditioned media. However, this approach did not induce the expression of key TFs at the protein level.

Date of Award	1 Aug 2018
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Richard Unwin (Supervisor), Mark Dunne (Supervisor) & Karen Cosgrove (Supervisor)