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

CARDOZO GIZZI, ANDRES M.; REMEDI, MONICA; GASTALDI, LAURA; CACERES, ALFREDO

Buenos Aires (CABA)

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

Sociedad Argentina de Neurociencias

During neuronal differentiation, neural progenitor cells must switchtheir gene expression programs to allow for the generation of neuronsand glial cells. This shift is produced by external cues togetherwith epigenetic mechanisms, such as histone post-translationalmodifications. Chemical modifications in chromatin correlate withits 3D architecture in the cell nucleus, and this organization isintegral in the control of gene expression.In this work, we used a human model of neural development derivedfrom induced pluripotent stem cells to study how chromatinpost-translational modifications change during the course ofdifferentiation. We measured the dynamics of H3K4me3, H3K27me3 andH3K9me3, epigenetic marks of euchromatin, facultative heterochromatinand constitutive heterochromatin, respectively. Based on confocalimaging data, we used Uniform Manifold Approximation and Projection(UMAP) to separate cell-type populations and characterize them duringthe time in culture. We found that epigenetic marks intensity and spatial pattern arehighly dependent on cell type. This initial characterization of thehuman model lays the ground to study how chromatin spatialorganization is required as an additional layer of gene expressionregulation. We propose a novel approach to discern new mechanisms oftranscriptional regulation in the context of human neuronaldifferentiation.p { line-height: 115%; margin-bottom: 0.25cm; background: transparent }