Session 3A Lectures by Fellows/Associates

Understanding post transcriptional mechanisms in neural development: Implications of induced pluripotent stem cells and organoids

Human central nervous system (CNS) development requires complex and precisely coordinated control of gene expression and intercellular interactions that result in the generation of a variety of cell types having distinct morphology and functions. A vast amount of knowledge of the fundamental molecular events underlying human neural development has been derived from model organisms. Despite studies using fetal tissues, the complexities of human brain development are poorly understood. However, recent advancement in the generation of human induced pluripotent stem cells (iPSCs) has transformed the studies of human brain development. MicroRNAs being the small non-coding RNAs, act as post-transcriptional regulators of gene expression. We have unlocked the regulatory role of miR-137 (a brain enriched miRNA) in neural development. This miRNA is dysregulated in several neurodevelopmental disorders including autism and intellectual disability. Our study provides first evidence in human neural stem cells (NSCs) derived from iPSCs that miR-137 inhibits proliferation while enhances neuronal differentiation and migration of NSCs. MiR-137 affects mitochondrial dynamics such as mitochondrial fission and fusion to achieve neuronal fate. A small part of my talk will be about retina which is a part of CNS involved in visual function. An excellent model to study retinal degenerative diseases is retinal organoids generated from human pluripotent stem cells. Molecular staging of retinal organoids revealed their competence with gene profiles of human fetal and adult retina using comparative transcriptomics.