Biology subjects

Loza, M.

Publications and source records attributed to Loza, M..

4 recordsLinked to original sources

bioRxiv2023

Comparative single-cell transcriptomic analysis reveals key differentiation drivers and the potential origin of the vertebrate retina

Despite known single-cell expression profiles in vertebrate retinas, understanding of their developmental and evolutionary expression patterns among homologous cell classes remains limited. We examined and compared approximately 240, 000 retinal cells from four species and found significant similarities among homologous cell classes, indicating inherent regulatory patterns. To understand these shared patterns, we constructed gene regulatory networks for each developmental stage for three of these species. We identified 690 regulons governed by 530 regulators across three species, along with 10 common cell class-specific regulators and 16 preserved regulons. RNA velocity analysis pinpointed conserved putative driver genes and regulators to retinal cell differentiation in both mouse and zebrafish. Investigation of the origins of retinal cells by examining conserved expression patterns between vertebrate retinal cells and invertebrate Ciona intestinalis photoreceptor-related cells implied functional similarities in light transduction mechanisms. Our findings offer insights into the evolutionarily conserved regulatory frameworks and differentiation drivers of vertebrate retinal cells.

bioinformatics↗

bioRxiv2023

Multi-omics computational analysis unveils the in-volvement of AP-1 and CTCF in hysteresis of chromatin states during macrophage polarization

Macrophages display extreme plasticity, and the mechanisms and applications of polarization and de/repolarization of macrophages have been extensively investigated. However, the regulation of macrophage hysteresis de/repolarization remains unclear. In this study, by using a large-scale computational analysis of macrophage omics data, we report a list of hysteresis genes that maintain their expression patterns after polarization after ulti- and de/repolarization. While the polarization in M1 macrophages leads to a higher level of hysteresis in genes associated with cell cycle progression, cell migration, and enhancement of the immune response, we found weak levels of hysteresis after M2 polarization. During the polarization process from M0 to M1 and back to M0, the factors IRFs/STAT, AP-1, and CTCF regulate hysteresis by altering their binding sites to the chromatin. Overall, our results show that a history of polarization can lead to hysteresis in gene expression and chromatin changes over a given period. This study contributes to the understanding of de-/repolarization memory in macrophages.

bioinformatics↗

bioRxiv2023

Epigenetic characterization of housekeeping core promoters and their importance in tumor suppression

There has been extensive research on describing cell type-specific (CTS) regulatory interactions, especially between enhancers and promoters. However, constitutively active interactions between CREs have been less studied. In this research, we elucidate the presence of around 11,000 housekeeping CREs (HK-CREs) and describe their main characteristics. Most of the HK-CREs are located in promoter regions, but contrary to expectations, they are not only the promoters of housekeeping genes and are involved in a broader role beyond housekeeping gene regulation. HK-CREs are conserved regions rich in unmethylated CpG sites. Their distribution across chromosomes highly correlates with that of protein-coding genes, and they interact with a large number of target genes in long-distance interactions. In the context of cancer, we observed a reduction in the activity of a subset of HK-CREs, particularly those located at the end of chromosome 19 and associated with zinc finger genes. We investigated the effect of these genes on samples from diverse cancer subtypes, observing a significant reduction in their expression due to aberrant methylation of their core promoters. Finally, an analysis of more than 5,000 patients from 17 cancer subtypes showed an increase in the survival probability of patients with higher expression of these genes, suggesting them as housekeeping tumor suppressor genes. Overall, our work unravels the presence of ubiquitously active CREs indispensable for the maintenance and stability of cells.

genomics↗

bioRxiv2022

Intercellular crosstalk in adult dental pulp is mediated by heparin-binding growth factors Pleiotrophin and Midkine

In-depth knowledge of the cellular and molecular composition of dental pulp (DP) and the crosstalk between DP cells that drive tissue homeostasis or regeneration are not well understood. To address these questions, we performed data analysis of publicly available single-cell transcriptomes of DP. This analysis revealed that DP resident fibroblasts have a unique gene expression profile when compared with fibroblasts from 5 other reference tissues: blood, bone marrow, adipose tissue, lung, and skin. Genes coded for heparin-binding growth-factors, pleiotrophin (PTN) and midkine (MDK), possessed the highest differential expression levels in DP fibroblasts. In addition, we identified extensive crosstalk between DP fibroblasts and several other DP cells, including Schwann cells, MSCs and odontoblasts. These findings suggest that fibroblast-derived growth factors regulate DP niches, and thus have a potential role as dental therapeutic targets.

cell biology↗