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Project
Uncovering the role of iron metabolism in beta cell differentiation, maturation, and function. (FWOAL1035)
Diabetes is a pandemic metabolic disorder. Current therapy strives
for glycemic control but fails to tackle the underlying beta cell defect.
Transplantation of pancreatic islets has shown that cell therapy can
result in insulin independence, but donor islets are scarce. Stem cellderived beta cells (SC-beta) may offer a reliable cell source for
transplantation. However, improved understanding of beta cell
differentiation, maturation and function is needed to generate
functional SC-beta cells. Beta cells specifically express high levels of
the transferrin receptor (TFRC), which mediates cellular iron uptake
from transferrin, compared to alpha and delta cells – the main
endocrine cell types in pancreatic islets. It is currently unclear why
this is the case and whether it is relevant for beta cell biology. In my
proposal, I aim to uncover the role of iron metabolism in beta cell
differentiation, maturation, and function. We will characterize
changes in iron metabolism over time in the main endocrine islet cell
types and disclose if in beta cells these changes relate to metabolic
and signaling shifts key for maturation. We will study how iron
deficiency affects beta cell development using novel mouse lines and
cutting-edge technologies with the aim of improving protocols to
generate SC-betas. This work will improve our understanding of
diabetes pathophysiology by disclosing new intricacies of beta cell
development and hopefully contribute to the development of a cellbased cure.
for glycemic control but fails to tackle the underlying beta cell defect.
Transplantation of pancreatic islets has shown that cell therapy can
result in insulin independence, but donor islets are scarce. Stem cellderived beta cells (SC-beta) may offer a reliable cell source for
transplantation. However, improved understanding of beta cell
differentiation, maturation and function is needed to generate
functional SC-beta cells. Beta cells specifically express high levels of
the transferrin receptor (TFRC), which mediates cellular iron uptake
from transferrin, compared to alpha and delta cells – the main
endocrine cell types in pancreatic islets. It is currently unclear why
this is the case and whether it is relevant for beta cell biology. In my
proposal, I aim to uncover the role of iron metabolism in beta cell
differentiation, maturation, and function. We will characterize
changes in iron metabolism over time in the main endocrine islet cell
types and disclose if in beta cells these changes relate to metabolic
and signaling shifts key for maturation. We will study how iron
deficiency affects beta cell development using novel mouse lines and
cutting-edge technologies with the aim of improving protocols to
generate SC-betas. This work will improve our understanding of
diabetes pathophysiology by disclosing new intricacies of beta cell
development and hopefully contribute to the development of a cellbased cure.
Date:1 Jan 2022 → Today
Keywords:Diabetes, beta cell, iron metabolism, cell therapy
Disciplines:Cell growth and development, Cell therapy, Metabolic diseases, Transcription and translation