Stem Cell Research and Beta Cell Replacement
Dr. Ingo Burtscher
First using mouse embryonic stem cells (mESCs) then using human induced pluripotent stem (iPSCs) cells Dr. Burtscher and his team generated numerous fluorescent reporter lines. These stem cell reporter lines are being used to understand how beta- or other pancreatic endocrine cell lineage form and how these lineage decisions can be influenced. Furthermore, they explore beta cell maturation which is closely related to their function. Applying various stress models, they try to understand how beta cell survival and glucose dependent insulin secretion are affected and how they can be restored.
The basis of in vitro differentiations are cellular and molecular processes occurring during early embryonic development. In our group we focus on a better understanding, how these processes lead to lineage specification, growth control and maturation of pancreatic endocrine lineages in the mouse. These findings we translate in vitro into the culture dish using induced pluripotent human stem cells (hiPSC).
Research Topics
Melis Akgün, PhD Student
Deciphering the underlying mechanism of pancreatic endocrine lineage decisions between Alpha and Beta cell fate. To this end we have generated a double fluorescent iPSC reporter line, where the earliest expressed Alpha- and Beta cell specific transcription factors ARX and PAX4 have been fluorescently labeled by Crispr/Cas9 based knock-in strategies. This iPSC line upon pancreatic b-cell differentiation serves for an easy readout, allowing us to determine Alpha and Beta cell fates in live cells at earliest time points during differentiation, sort these populations and analyse their fate, plasticity and the use drugs to influence this fate decisions.
The Institute of Diabetes and Regeneration Research at Helmholtz Zentrum München and the global pharmaceutical company Eli Lilly and Company (Lilly) have entered a new strategic research collaboration in the field of pancreatic beta cell regeneration. The joint goal is to improve and accelerate treatment of diabetes mellitus.
This new collaboration between Helmholtz Zentrum München and Lilly will focus on the identification, validation and targeting of novel pathways and molecules for triggering endogenous beta cell regeneration. The long-term goal is to develop new therapies that preserve and/or restore mass and functionality of patient’s remaining beta cells during diabetes progression.
Melis Akgün, PhD Student
Deciphering the underlying mechanism of pancreatic endocrine lineage decisions between Alpha and Beta cell fate. To this end we have generated a double fluorescent iPSC reporter line, where the earliest expressed Alpha- and Beta cell specific transcription factors ARX and PAX4 have been fluorescently labeled by Crispr/Cas9 based knock-in strategies. This iPSC line upon pancreatic b-cell differentiation serves for an easy readout, allowing us to determine Alpha and Beta cell fates in live cells at earliest time points during differentiation, sort these populations and analyse their fate, plasticity and the use drugs to influence this fate decisions.
The Institute of Diabetes and Regeneration Research at Helmholtz Zentrum München and the global pharmaceutical company Eli Lilly and Company (Lilly) have entered a new strategic research collaboration in the field of pancreatic beta cell regeneration. The joint goal is to improve and accelerate treatment of diabetes mellitus.
This new collaboration between Helmholtz Zentrum München and Lilly will focus on the identification, validation and targeting of novel pathways and molecules for triggering endogenous beta cell regeneration. The long-term goal is to develop new therapies that preserve and/or restore mass and functionality of patient’s remaining beta cells during diabetes progression.
Publications
Read more2022 Scientific Article in Life Science Alliance
Mitochondrial impairment and intracellular reactive oxygen species alter primary cilia morphology.
2022 Scientific Article in Nature Communications
Synaptotagmin-13 orchestrates pancreatic endocrine cell egression and islet morphogenesis.
2021 Scientific Article in The CRISPR Journal
Increasing gene editing efficiency for CRISPR-Cas9 by small RNAs in pluripotent stem cells.
2021 Nature Cell Biology
Publisher Correction: Epithelial cell plasticity drives endoderm formation during gastrulation.
2021 Scientific Article in Nature Cell Biology
Epithelial cell plasticity drives endoderm formation during gastrulation.
2021 Nature Cell Biology
Author Correction: Non-canonical Wnt/PCP signalling regulates intestinal stem cell lineage priming towards enteroendocrine and Paneth cell fates.
2021 Scientific Article in Nature Communications
Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population.
2021 Scientific Article in Biology of Reproduction
Anatomical and cellular heterogeneity in the mouse oviduct- its potential roles in reproduction and preimplantation development.
2021 Scientific Article in Molecular Metabolism
CD81 marks immature and dedifferentiated pancreatic β-cells.
2021 Scientific Article in International Journal of Molecular Sciences