Revisiting the immunocytochemical detection of Neurogenin 3 expression in mouse and man

Abstract

).During embryonic development, endocrine cells of the pancreas are specified from multipotent progenitors. The transcription factor Neurogenin 3 (NEUROG3) is critical for this development and it has been shown that all endocrine cells of the pancreas arise from endocrine progenitors expressing NEUROG3. A thorough understanding of the role of NEUROG3 during development, directed differentiation of pluripotent stem cells and in models of cellular reprogramming, will guide future efforts directed at finding novel sources of β-cells for cell replacement therapies. In this article, we review the expression and function of NEUROG3 in both mouse and human and present the further characterization of a monoclonal antibody directed against NEUROG3. This antibody has been previously been used for detection of both mouse and human NEUROG3. However, our results suggest that the epitope recognized by this antibody is specific to mouse NEUROG3. Thus, we have also generated a monoclonal antibody specifically recognizing human NEUROG3 and present the characterization of this antibody here.Together, these antibodies will provide useful tools for future studies of NEUROG3 expression, and the data presented in this article suggest that recently described expression patterns of NEUROG3 in human foetal and adult pancreas should be re-examined. 1 Lessons from developmental biology have greatly aided advances in both of these approaches, but it has become evident that we still lack a complete understanding of the mechanisms involved in the commitment to the endocrine lineage and the specification of the individual endocrine cell types of the pancreas.In this article, we review the expression of the basic helix-loophelix transcription factor Neurogenin 3 (NEUROG3) and discuss its role in the endocrine specification during pancreas development and reprogramming of adult non-endocrine cells to β-cells. We also present a more extensive characterization of a monoclonal antibody (F25A1B3) raised against mouse NEUROG3 that we have previously developed (Figure 1). 2 This antibody was raised against mouse NEU-ROG3 but has also been used in several studies of human NEUROG3.Our data suggest that the specificity of this antibody is primarily directed towards mouse NEUROG3 and hence we also present the

Scientific Advances in Diabetes: The Impact of the Innovative Medicines Initiative

“…New potential therapeutic targets were suggested for the treatment of accelerated atherosclerosis in diabetic patients ( 161 ) (SUMMIT), for treating glomerular disease in T2D patients ( 36 , 135 , 162 – 164 ) (SUMMIT), for T2D patients with obesity ( 165 ) (EMIF), for counteracting hyperglycemia in individuals with T2D ( 166 ) (IMIDIA), for prevent or reverse β-cell loss [IMIDIA ( 167 ), StemBANCC ( 114 , 116 , 168 , 169 ) and INNODIA ( 14 , 90 , 120 , 121 , 170 – 172 )], and for diabetes with a focus on the use of new concepts such as epitranscriptome-based therapy by RHAPSODY ( 173 ), StemBANCC ( 114 – 116 , 168 , 169 , 174 ), EMIF ( 86 ), and RHAPSODY ( 173 ). In terms of novel pharmacologic agents for T2D, SUMMIT developed the clinical trials of Aleglitazar ( 175 ), RAAS inhibitors ( 176 ), and supported the use of low-dose aspirin for the secondary prevention of cerebro-cardiovascular events ( 177 ).…”

PDX-1: A Promising Therapeutic Target to Reverse Diabetes

“…Neurogenin 3 ( Ngn3 ) is critical for inducing endocrine islet cell differentiation from embryonic pancreatic progenitors, and all pancreatic endocrine cells arise from endocrine progenitors expressing Ngn 3 [ 90 ]. PDX-1 directly regulates Ngn 3 expression [ 91 ].…”

Gene Signatures of NEUROGENIN3+ Endocrine Progenitor Cells in the Human Pancreas

“…The expression of NEUROG3 gradually reduces in abundance as the development progresses (20)(21)(22). It remains controversial as to whether NEUROG3 is expressed in the post-development human pancreas (20,(23)(24)(25), possibly reflecting the detection limit of immunolabeling approaches and the sensitivities as well as specificities of antibodies utilized in some of the studies (26).…”