Epigenetic marks dynamics during neuronal differentiation from human induced pluripotent stem cells

CARDOZO-GIZZI A; REMEDI MM; GASTALDI L; CACERES A

Buenos Aires

Congreso; XXXVII Annual Meeting of the Sociedad Argentina de Investigación en Neurociencias (SAN); 2022

Sociledad Argentina de Investigacion en Neurociencias

During neuronal differentiation, neural progenitor cells must switch their geneexpression programs to allow for the generation of neurons and glial cells. This shift isproduced by external cues together with epigenetic mechanisms, such as histone post-translational modifications. Chemical modifications in chromatin correlate with its 3Darchitecture in the cell nucleus, and this organization is integral in the control of geneexpression.In this work, we used a human model of neural development derived from inducedpluripotent stem cells to study how chromatin post-translational modifications change duringthe course of differentiation. We measured the dynamics of H3K4me3, H3K27me3 andH3K9me3, epigenetic marks of euchromatin, facultative heterochromatin and constitutiveheterochromatin, respectively. Based on confocal imaging data, we used Uniform ManifoldApproximation and Projection (UMAP) to separate cell-type populations and characterizethem during the time in culture.We found that epigenetic marks intensity and spatial pattern are highly dependent oncell type. This initial characterization of the human model lays the ground to study howchromatin spatial organization is required as an additional layer of gene expressionregulation. We propose a novel approach to discern new mechanisms of transcriptionalregulation in the context of human neuronal differentiation.