Chromosome Modeling on Downsampled Hi-C Maps Enhances the Compartmentalization Signal.

The human genome is organized within a nucleus where chromosomes fold into an ensemble of different conformations. Chromosome conformation capture techniques such as Hi-C provide information about the genome architecture by creating a 2D heat map. Initially, Hi-C map experiments were performed in human interphase cell lines. Recently, efforts were expanded to several different organisms, cell lines, tissues, and cell cycle phases where obtaining high-quality maps is challenging. Poor sampled Hi-C maps present high sparse matrices where compartments located far from the main diagonal are difficult to observe. Aided by recently developed models for chromatin folding and dynamics investigation, we introduce a framework to enhance the compartments' information far from the diagonal observed in experimental sparse matrices. The simulations were performed using the Open-MiChroM platform aided by new trained parameters in the minimal chromatin model (MiChroM) energy function. The simulations optimized on a downsampled experimental map (10% of the original data) allow the prediction of a contact frequency similar to that of the complete (100%) experimental Hi-C. The modeling results open a discussion on how simulations and modeling can increase the statistics and help fill in some Hi-C regions not captured by poor sampling experiments. Open-MiChroM simulations allow us to explore the 3D genome organization of different organisms, cell lines, and cell phases that often do not produce high-quality Hi-C maps.

Long-distance effects of inflammation on differentiation of adult spinal cord neural stem/progenitor cells.

Studies in multiple sclerosis have demonstrated that normal-appearing white matter can harbor pathological changes. Here we investigated the effects of neuroinflammation, modeled by experimental autoimmune encephalomyelitis (EAE) on neural stem/progenitor cells (NPCs) located distally to inflammatory foci. We observed that EAE-derived NPCs had a lower capacity to differentiate into oligodendrocytes and an increased neuronal differentiation than control NPCs. This finding was corroborated with changes in gene expression of early differentiation genes. We conclude that inflammation has a long range effect on the NPCs in the diseased central nervous system, reaching NPC populations outside the lesion sites.