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Project
Deciphering the involvement of iron metabolism in beta cell differentiation, maturation, and function. (FWOTM1142)
Diabetes mellitus is a pandemic metabolic disorder characterized by
chronic hyperglycemia. Today’s treatments ensure glycemic control
but fail to tackle the underlying beta cell defect. Although cell therapy
via transplantation of islets of Langerhans can result in insulin
independence, donor islets remain scarce. Stem cell derived beta
cells (SC-beta) may offer an alternative and abundant cell source for
transplantation, however, improved understanding of beta cell
differentiation, maturation and function is still needed to generate
fully functional SC-beta cells. Beta cells, in contrast to alpha and
delta cells – the main endocrine cell types in pancreatic islets -,
specifically express high levels of the transferrin receptor (TFRC) that
mediates cellular uptake of iron-bound transferrin. Why this is the
case and whether it is relevant for beta cell biology remains an
unexplored feature in the field of beta cell developmental research.
In my proposal, I aim to reveal the role of iron metabolism in beta cell
differentiation, maturation, and function. Using novel mouse strains
and cutting-edge technologies, I will investigate how iron deficiency
affects beta cell development with the ultimate goal to improve
current protocols to generate SC-beta cells that could be used for cell
therapy. Overall, this work will improve the understanding of diabetes
pathophysiology by disclosing new intricacies of beta cell
development and will pave the way for a cell-based cure.
chronic hyperglycemia. Today’s treatments ensure glycemic control
but fail to tackle the underlying beta cell defect. Although cell therapy
via transplantation of islets of Langerhans can result in insulin
independence, donor islets remain scarce. Stem cell derived beta
cells (SC-beta) may offer an alternative and abundant cell source for
transplantation, however, improved understanding of beta cell
differentiation, maturation and function is still needed to generate
fully functional SC-beta cells. Beta cells, in contrast to alpha and
delta cells – the main endocrine cell types in pancreatic islets -,
specifically express high levels of the transferrin receptor (TFRC) that
mediates cellular uptake of iron-bound transferrin. Why this is the
case and whether it is relevant for beta cell biology remains an
unexplored feature in the field of beta cell developmental research.
In my proposal, I aim to reveal the role of iron metabolism in beta cell
differentiation, maturation, and function. Using novel mouse strains
and cutting-edge technologies, I will investigate how iron deficiency
affects beta cell development with the ultimate goal to improve
current protocols to generate SC-beta cells that could be used for cell
therapy. Overall, this work will improve the understanding of diabetes
pathophysiology by disclosing new intricacies of beta cell
development and will pave the way for a cell-based cure.
Date:1 Nov 2022 → Today
Keywords:Diabetes, Iron metabolism, Cellular maturation
Disciplines:Cell signalling, Cell therapy, Endocrinology, Metabolic diseases