Project description:Islet β-cells from newborn mammals need a maturation process to become mature functional beta cells. The detailed molecular mechanisms were not completely understood. This study was designed to reveal the dynamic gene expression changes during pancreatic beta-cell maturation in postnatal mice. We also want to understand how genetic mutations that impair beta-cell function change the genetic networks involved in the beta-cell maturation process. For these aims, pancreatic beta cells were isolated at P1 islets based on the expression of a MipeGFP transgene in a genetic background with pancreatic specific inactivation of Myt1, Myt1L, and St18 (denoted as MytDelpanc; MipeGFP).
Project description:The intent of this experiment was to determine MAFB binding sites in human pancreatic beta cells. This is particularly relevant as MAFB is not expressed in mature rodent beta cells; thus, it may perform unique functions in human. Sequencing was performed following IP with an anti-MAFB antibody using chromatin isolated from the human pancreatic beta cell line, EndoCBH2 cells. Cells were proliferating and untreated when collected.
Project description:The zinc finger factor Insm1 is known to regulate differentiation of pancreatic β cells during development, Here we show that Insm1 is essential for the maintenance of functionally mature pancreatic β cells in mice. We used microarrays to analyse the global gene expression after deletion of insm1 in adult pancreatic β cells and identified functional important genes and immature islets releated genes deregulated in the mutatant islets.
Project description:This experiment used RNA-Seq technology to examine transcription profile in FACS-sorted MIP-EGFP+ mouse pancreatic cells at E16.5 (nascent beta cells) and P60 (mature beta cells). Such an analysis should reveal the gene transcription alterations for beta cell development and for function.
Project description:Type 2 Diabetes Mellitus (T2D), a multifactorial disease, can result from perturbations in numerous pancreatic genes. We describe a previously unanticipated role for Sox9, a transcriptional regulator of embryonic pancreas and endocrine cell development, in mature beta cells. Our data demonstrate that Sox9 has continued function in beta cells as they mature, and elimination of Sox9 compromises beta cell activities. Sox9-depleted rodent beta cells fail to appropriately secrete insulin and exhibit glucose intolerance in aging animals, mimicking the progressive degeneration observed in T2D. Human beta cells lacking SOX9 are functionally impaired with stunted first phase insulin secretion. In both rodent and human, Sox9 loss in beta cells disrupts alternative splicing patterns, with significant implications for maintenance of cellular function. Thus, our data uncover a novel, unprecedented role for a developmental transcription factor in mature beta cell function.
Project description:Type 2 Diabetes Mellitus (T2D), a multifactorial disease, can result from perturbations in numerous pancreatic genes. We describe a previously unanticipated role for Sox9, a transcriptional regulator of embryonic pancreas and endocrine cell development, in mature beta cells. Our data demonstrate that Sox9 has continued function in beta cells as they mature, and elimination of Sox9 compromises beta cell activities. Sox9-depleted rodent beta cells fail to appropriately secrete insulin and exhibit glucose intolerance in aging animals, mimicking the progressive degeneration observed in T2D. Human beta cells lacking SOX9 are functionally impaired with stunted first phase insulin secretion. In both rodent and human, Sox9 loss in beta cells disrupts alternative splicing patterns, with significant implications for maintenance of cellular function. Thus, our data uncover a novel, unprecedented role for a developmental transcription factor in mature beta cell function.
Project description:Transcriptional profiling of a directed differentiation time course converting human embryonic stem cells (hES) into immature pancreatic beta cell precursors.