Cellular and Molecular Neurobiology
Author: Andres Mauricio Cardozo Gizzi | email: andres.cardozo@iucbc.edu.ar
Andrés Cardozo Gizzi 1°, Monica Remedi 1°, Laura Gastaldi 1°, Alfredo Cáceres 1°
1° Centro de Investigación en Medicina Traslacional “Severo Amuchástegui” (CIMETSA) – Instituto Universitario Ciencias Biomédicas Córdoba (IUCBC)
During neuronal differentiation, neural progenitor cells must switch their gene expression programs to allow for the generation of neurons and glial cells. This shift is produced by external cues together with epigenetic mechanisms, such as histone post-translational modifications. Chemical modifications in chromatin correlate with its 3D architecture in the cell nucleus, and this organization is integral in the control of gene expression. In this work, we used a human model of neural development derived from induced pluripotent stem cells to study how chromatin post-translational modifications change during the course of differentiation. We measured the dynamics of H3K4me3, H3K27me3 and H3K9me3, epigenetic marks of euchromatin, facultative heterochromatin and constitutive heterochromatin, respectively. Based on confocal imaging data, we used Uniform Manifold Approximation and Projection (UMAP) to separate cell-type populations and characterize them during the time in culture. We found that epigenetic marks intensity and spatial pattern are highly dependent on cell type. This initial characterization of the human model lays the ground to study how chromatin spatial organization is required as an additional layer of gene expression regulation. We propose a novel approach to discern new mechanisms of transcriptional regulation in the context of human neuronal differentiation.