NEUROD1: Transcriptional and Epigenetic Regulator of Human and Mouse Neuronal and Endocrine Cell Lineage Programs

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2024 Aug 6

PMID 39105169

Authors

Gabriela Pavlinkova

Ondrej Smolik

Affiliations

Soon will be listed here.

Abstract

Transcription factors belonging to the basic helix-loop-helix (bHLH) family are key regulators of cell fate specification and differentiation during development. Their dysregulation is implicated not only in developmental abnormalities but also in various adult diseases and cancers. Recently, the abilities of bHLH factors have been exploited in reprogramming strategies for cell replacement therapy. One such factor is NEUROD1, which has been associated with the reprogramming of the epigenetic landscape and potentially possessing pioneer factor abilities, initiating neuronal developmental programs, and enforcing pancreatic endocrine differentiation. The review aims to consolidate current knowledge on NEUROD1's multifaceted roles and mechanistic pathways in human and mouse cell differentiation and reprogramming, exploring NEUROD1 roles in guiding the development and reprogramming of neuroendocrine cell lineages. The review focuses on NEUROD1's molecular mechanisms, its interactions with other transcription factors, its role as a pioneer factor in chromatin remodeling, and its potential in cell reprogramming. We also show a differential potential of NEUROD1 in differentiation of neurons and pancreatic endocrine cells, highlighting its therapeutic potential and the necessity for further research to fully understand and utilize its capabilities.

References

Ikematsu Y, Tanaka K, Toyokawa G, Ijichi K, Ando N, Yoneshima Y . NEUROD1 is highly expressed in extensive-disease small cell lung cancer and promotes tumor cell migration. Lung Cancer. 2020; 146:97-104. DOI: 10.1016/j.lungcan.2020.05.012. View

Akol I, Izzo A, Gather F, Strack S, Heidrich S, O hAilin D . Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome. Proc Natl Acad Sci U S A. 2023; 120(2):e2122467120. PMC: 9926245. DOI: 10.1073/pnas.2122467120. View

Ren B, Tao C, Swan M, Joachim N, Martiniello-Wilks R, Nassif N . Pancreatic Transdifferentiation and Glucose-Regulated Production of Human Insulin in the H4IIE Rat Liver Cell Line. Int J Mol Sci. 2016; 17(4):534. PMC: 4848990. DOI: 10.3390/ijms17040534. View

Zhang T, Wang H, Saunee N, Breslin M, Lan M . Insulinoma-associated antigen-1 zinc-finger transcription factor promotes pancreatic duct cell trans-differentiation. Endocrinology. 2010; 151(5):2030-9. PMC: 2869251. DOI: 10.1210/en.2009-1224. View

Yatoh S, Akashi T, Chan P, Kaneto H, Sharma A, Bonner-Weir S . NeuroD and reaggregation induce beta-cell specific gene expression in cultured hepatocytes. Diabetes Metab Res Rev. 2006; 23(3):239-49. DOI: 10.1002/dmrr.678. View

Neptune E, Podowski M, Calvi C, Cho J, Garcia J, Tuder R . Targeted disruption of NeuroD, a proneural basic helix-loop-helix factor, impairs distal lung formation and neuroendocrine morphology in the neonatal lung. J Biol Chem. 2008; 283(30):21160-9. PMC: 2475704. DOI: 10.1074/jbc.M708692200. View

Vermeiren S, Bellefroid E, Desiderio S . Vertebrate Sensory Ganglia: Common and Divergent Features of the Transcriptional Programs Generating Their Functional Specialization. Front Cell Dev Biol. 2020; 8:587699. PMC: 7649826. DOI: 10.3389/fcell.2020.587699. View

Imayoshi I, Kageyama R . bHLH factors in self-renewal, multipotency, and fate choice of neural progenitor cells. Neuron. 2014; 82(1):9-23. DOI: 10.1016/j.neuron.2014.03.018. View

Wang L, Zhang C . In vivo glia-to-neuron conversion: pitfalls and solutions. Dev Neurobiol. 2022; 82(5):367-374. PMC: 9337910. DOI: 10.1002/dneu.22880. View

10.

Sommer L, Ma Q, Anderson D . neurogenins, a novel family of atonal-related bHLH transcription factors, are putative mammalian neuronal determination genes that reveal progenitor cell heterogeneity in the developing CNS and PNS. Mol Cell Neurosci. 1996; 8(4):221-41. DOI: 10.1006/mcne.1996.0060. View

11.

Pongor L, Tlemsani C, Elloumi F, Arakawa Y, Jo U, Gross J . Integrative epigenomic analyses of small cell lung cancer cells demonstrates the clinical translational relevance of gene body methylation. iScience. 2022; 25(11):105338. PMC: 9619308. DOI: 10.1016/j.isci.2022.105338. View

12.

Malecki M, Jhala U, Antonellis A, Fields L, Doria A, Orban T . Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nat Genet. 1999; 23(3):323-8. DOI: 10.1038/15500. View

13.

Sugimori M, Nagao M, Bertrand N, Parras C, Guillemot F, Nakafuku M . Combinatorial actions of patterning and HLH transcription factors in the spatiotemporal control of neurogenesis and gliogenesis in the developing spinal cord. Development. 2007; 134(8):1617-29. DOI: 10.1242/dev.001255. View

14.

Horikawa Y, Enya M . Genetic Dissection and Clinical Features of MODY6 (NEUROD1-MODY). Curr Diab Rep. 2019; 19(3):12. DOI: 10.1007/s11892-019-1130-9. View

15.

de Martin X, Sodaei R, Santpere G . Mechanisms of Binding Specificity among bHLH Transcription Factors. Int J Mol Sci. 2021; 22(17). PMC: 8431614. DOI: 10.3390/ijms22179150. View

16.

Casey B, Kollipara R, Pozo K, Johnson J . Intrinsic DNA binding properties demonstrated for lineage-specifying basic helix-loop-helix transcription factors. Genome Res. 2018; 28(4):484-496. PMC: 5880239. DOI: 10.1101/gr.224360.117. View

17.

Zhao M, Amiel S, Ajami S, Jiang J, Rela M, Heaton N . Amelioration of streptozotocin-induced diabetes in mice with cells derived from human marrow stromal cells. PLoS One. 2008; 3(7):e2666. PMC: 2441861. DOI: 10.1371/journal.pone.0002666. View

18.

Bertrand N, Castro D, Guillemot F . Proneural genes and the specification of neural cell types. Nat Rev Neurosci. 2002; 3(7):517-30. DOI: 10.1038/nrn874. View

19.

Liu M, Pleasure S, Collins A, Noebels J, Naya F, Tsai M . Loss of BETA2/NeuroD leads to malformation of the dentate gyrus and epilepsy. Proc Natl Acad Sci U S A. 2000; 97(2):865-70. PMC: 15422. DOI: 10.1073/pnas.97.2.865. View

20.

Dennis D, Han S, Schuurmans C . bHLH transcription factors in neural development, disease, and reprogramming. Brain Res. 2018; 1705:48-65. DOI: 10.1016/j.brainres.2018.03.013. View