دورية أكاديمية
Temporal Transcriptome Analysis Reveals Dynamic Gene Expression Patterns Driving β-Cell Maturation
| العنوان: | Temporal Transcriptome Analysis Reveals Dynamic Gene Expression Patterns Driving β-Cell Maturation |
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| المؤلفون: | Sanavia T., Huang C., Manduchi E., Xu Y., Dadi P. K., Potter L. A., Jacobson D. A., Di Camillo B., Magnuson M. A., Stoeckert C. J., Gu G. |
| المساهمون: | Sanavia, T., Huang, C., Manduchi, E., Xu, Y., Dadi, P. K., Potter, L. A., Jacobson, D. A., Di Camillo, B., Magnuson, M. A., Stoeckert, C. J., Gu, G. |
| بيانات النشر: | Frontiers Media S.A. |
| سنة النشر: | 2021 |
| المجموعة: | Padua Research Archive (IRIS - Università degli Studi di Padova) |
| مصطلحات موضوعية: | calcium influx, glucose-induced insulin secretion, RNA sequencing, time-series gene expression, vesicle release, β-cell maturation |
| الوصف: | Newly differentiated pancreatic β cells lack proper insulin secretion profiles of mature functional β cells. The global gene expression differences between paired immature and mature β cells have been studied, but the dynamics of transcriptional events, correlating with temporal development of glucose-stimulated insulin secretion (GSIS), remain to be fully defined. This aspect is important to identify which genes and pathways are necessary for β-cell development or for maturation, as defective insulin secretion is linked with diseases such as diabetes. In this study, we assayed through RNA sequencing the global gene expression across six β-cell developmental stages in mice, spanning from β-cell progenitor to mature β cells. A computational pipeline then selected genes differentially expressed with respect to progenitors and clustered them into groups with distinct temporal patterns associated with biological functions and pathways. These patterns were finally correlated with experimental GSIS, calcium influx, and insulin granule formation data. Gene expression temporal profiling revealed the timing of important biological processes across β-cell maturation, such as the deregulation of β-cell developmental pathways and the activation of molecular machineries for vesicle biosynthesis and transport, signal transduction of transmembrane receptors, and glucose-induced Ca2+ influx, which were established over a week before β-cell maturation completes. In particular, β cells developed robust insulin secretion at high glucose several days after birth, coincident with the establishment of glucose-induced calcium influx. Yet the neonatal β cells displayed high basal insulin secretion, which decreased to the low levels found in mature β cells only a week later. Different genes associated with calcium-mediated processes, whose alterations are linked with insulin resistance and deregulation of glucose homeostasis, showed increased expression across β-cell stages, in accordance with the temporal acquisition of proper GSIS. ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/34017831; info:eu-repo/semantics/altIdentifier/wos/WOS:000651408800001; volume:9; firstpage:648791; journal:FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY; http://hdl.handle.net/11577/3415044Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85105987127 |
| DOI: | 10.3389/fcell.2021.648791 |
| الإتاحة: | https://doi.org/10.3389/fcell.2021.648791Test http://hdl.handle.net/11577/3415044Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.F13D2336 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fcell.2021.648791 |
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