The postnatal pancreatic microenvironment guides β cell maturation through BMP4 production
| Autor: | Lina Sakhneny, Francesca M. Spagnoli, Laura Mueller, Anat Schonblum, Guzel Burganova, Abigail Isaacson, Heather Wilson, Sivan Azaria, Limor Landsman, Alona Epshtein |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Genetically modified mouse
medicine.medical_treatment Organogenesis Cell Gene Expression Mice Transgenic Bone Morphogenetic Protein 4 Biology Cell Maturation General Biochemistry Genetics and Molecular Biology Islets of Langerhans Mice Insulin-Secreting Cells Insulin Secretion medicine Glucose homeostasis Animals Homeostasis Humans Insulin Secretion Induced pluripotent stem cell Molecular Biology Pancreas Homeodomain Proteins geography geography.geographical_feature_category Cell Differentiation Cell Biology Islet Cell biology Mice Inbred C57BL medicine.anatomical_structure Glucose Animals Newborn Gene Expression Regulation Trans-Activators Pericytes Developmental Biology |
| Zdroj: | Developmental cell. 56(19) |
| ISSN: | 1878-1551 |
| Popis: | Glucose homeostasis depends on regulated insulin secretion from pancreatic β cells, which acquire their mature phenotype postnatally. The functional maturation of β cells is regulated by a combination of cell-autonomous and exogenous factors; the identity of the latter is mostly unknown. Here, we identify BMP4 as a critical component through which the pancreatic microenvironment regulates β cell function. By combining transgenic mouse models and human iPSCs, we show that BMP4 promotes the expression of core β cell genes and is required for proper insulin production and secretion. We identified pericytes as the primary pancreatic source of BMP4, which start producing this ligand midway through the postnatal period, at the age β cells mature. Overall, our findings show that the islet niche directly promotes β cell functional maturation through the timely production of BMP4. Our study highlights the need to recapitulate the physiological postnatal islet niche for generating fully functional stem-cell-derived β cells for cell replacement therapy for diabetes. |
| Databáze: | OpenAIRE |
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