Organogenesis relies on SoxC transcription factors for the survival of neural and mesenchymal progenitors

During organogenesis, neural and mesenchymal progenitor cells give rise to many cell lineages, but their molecular requirements for self-renewal and lineage decisions are incompletely understood. In this study, we show that their survival critically relies on the redundantly acting SoxC transcription factors Sox4, Sox11 and Sox12. The more SoxC alleles that are deleted in mouse embryos, the more severe and widespread organ hypoplasia is. SoxC triple-null embryos die at midgestation unturned and tiny, with normal patterning and lineage specification, but with massively dying neural and mesenchymal progenitor cells. Specific inactivation of SoxC genes in neural and mesenchymal cells leads to selective apoptosis of these cells, suggesting SoxC cell-autonomous roles. Tead2 functionally interacts with SoxC genes in embryonic development, and is a direct target of SoxC proteins. SoxC genes therefore ensure neural and mesenchymal progenitor cell survival, and function in part by activating this transcriptional mediator of the Hippo signalling pathway

2-Hydroxylethyl methacrylate (HEMA), a tooth restoration component, exerts its genotoxic effects in human gingival fibroblasts trough methacrylic acid, an immediate product of its degradation

HEMA (2-hydroxyethyl methacrylate), a methacrylate commonly used in dentistry, was reported to induce genotoxic effects, but their mechanism is not fully understood. HEMA may be degraded by the oral cavity esterases or through mechanical stress following the chewing process. Methacrylic acid (MAA) is the primary product of HEMA degradation. In the present work we compared cytotoxic and genotoxic effects induced by HEMA and MAA in human gingival fibroblasts (HGFs). A 6-h exposure to HEMA or MAA induced a weak decrease in the viability of HGFs. Neither HEMA nor MAA induced strand breaks in the isolated plasmid DNA, but both compounds evoked DNA damage in HGFs, as evaluated by the alkaline comet assay. Oxidative modifications to the DNA bases were monitored by the DNA repair enzymes Endo III and Fpg. DNA damage induced by HEMA and MAA was not persistent and was removed during a 120 min repair incubation. Results from the neutral comet assay indicated that both compounds induced DNA double strand breaks (DSBs) and they were confirmed by the γ-H2AX assay. Both compounds induced apoptosis and perturbed the cell cycle. Therefore, methacrylic acid, a product of HEMA degradation, may be involved in its cytotoxic and genotoxic action

SOXC and MiR17-92 gene expression profiling defines two subgroups with different clinical outcome in mantle cell lymphoma

Mantle cell lymphoma (MCL) is a heterogeneous B-cell lymphoid malignancy where most patients follow an aggressive clinical course whereas others are associated with an indolent performance. SOX4, SOX11, and SOX12 belong to SOXC family of transcription factors involved in embryonic neurogenesis and tissue remodeling. Among them, SOX11 has been found aberrantly expressed in most aggressive MCL patients, being considered a reliable biomarker in the pathology. Several studies have revealed that microRNAs (miRs) from the miR-17-92 cluster are among the most deregulated miRNAs in human cancers, still little is known about this cluster in MCL. In this study we screened the transcriptional profiles of 70 MCL patients for SOXC cluster and miR17, miR18a, miR19b and miR92a, from the miR-17-92 cluster. Gene expression analysis showed higher SOX11 and SOX12 levels compared to SOX4 (P≤0.0026). Moreover we found a negative correlation between the expression of SOX11 and SOX4 (P<0.0001). miR17-92 cluster analysis showed that miR19b and miR92a exhibited higher levels than miR17 and miR18a (P<0.0001). Unsupervised hierarchical clustering revealed two subgroups with significant differences in relation to aggressive MCL features, such as blastoid morphological variant (P=0.0412), nodal presentation (P=0.0492), CD5+ (P=0.0004) and shorter overall survival (P<0.0001). Together, our findings show for the first time an association between the differential expression profiles of SOXC and miR17-92 clusters in MCL and also relate them to different clinical subtypes of the disease adding new biological information that may contribute to a better understanding of this pathology.Fil: Roisman, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Huamán Garaicoa, Fuad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. FUNDALEU; ArgentinaFil: Metrebian, Fernanda. Instituto de Investigaciones Hematologicas; ArgentinaFil: Narbaitz, Marina. FUNDALEU; Argentina. Instituto de Investigaciones Hematologicas; ArgentinaFil: Kohan, Dana. Hospital Italiano; ArgentinaFil: Garcia Rivello, Hernan Jorge. Hospital Italiano; ArgentinaFil: Fernandez, Isolda. FUNDALEU; ArgentinaFil: Pavlovsky, Astrid. FUNDALEU; ArgentinaFil: Pavlovsky, Miguel. FUNDALEU; ArgentinaFil: Hernández, Luis. Institut d’Investigacions Biome'diques August Pii Sunyer; EspañaFil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin