[en] Restoring damaged β-cells in diabetic patients by harnessing the plasticity of other
pancreatic cells raises the questions of the efficiency of the process and of the
functionality of the new Insulin-expressing cells. To overcome the weak regenerative
capacity of mammals, we used regeneration-prone zebrafish to study β-cells arising
following destruction. We show that most new insulin cells differ from the original β-
cells as they are Somatostatin+ Insulin+, but are nevertheless functional and
normalize glycemia. These bi-hormonal cells are transcriptionally close to a subset
of δ-cells in normal islets characterized by the expression of somatostatin 1.1
(sst1.1), the β-cell genes pdx1, slc2a2 and gck, and the machinery for glucoseinduced
Insulin secretion. β-cell destruction triggers massive sst1.1 δ-cell conversion
to bihormonal cells. Our work shows that their pro- β-cell identity predisposes this
zebrafish δ-cell subpopulation to efficient age-independent neogenesis of
Insulin-producing cells and provides clues to restoring functional β-cells in mammalian
diabetes models.
Characterization of the regenerated Insulin-producing cells following pancreatic β-cell destruction in zebrafish
Defense date :
18 October 2021
Number of pages :
206
Institution :
ULiège - Université de Liège
Degree :
Doctor of Philosophy in Sciences
Promotor :
Manfroid, Isabelle ; Université de Liège - ULiège > GIGA > GIGA Stem Cells - Zebrafish Development and Disease Model
President :
Struman, Ingrid ; Université de Liège - ULiège > Département des sciences de la vie
Secretary :
Peers, Bernard ; Université de Liège - ULiège > GIGA > GIGA Stem Cells - Zebrafish Development and Disease Model
Jury member :
Tarifeño, Estefania
Gilon, Patrick
Muller, Marc ; Université de Liège - ULiège > GIGA > GIGA I3 - Laboratory for Organogenesis and Regeneration
Funders :
Doctoral fellowship from the Chilean National Agency for Research and Development (ANID), by the Program BECAS CHILE 2016 – 72170660 National Belgian Funds for Scientific Research FNRS-FRS Belgian FNRS under EOS Project No. 30826052 Léon Fredericq funding, operating-equipment subsidy 2018-2019 and 2019-2020