γH2AX in mouse embryonic stem cells: Distribution during differentiation and following γ-irradiation.

Phosphorylated histone H2AX (γH2AX) represents a sensitive molecular marker of DNA double-strand breaks (DSBs) and is implicated in stem cell biology. We established a model of mouse embryonic stem cell (mESC) differentiation and examined the dynamics of γH2AX foci during the process. Our results revealed high numbers of γH2AX foci in undifferentiated mESCs, decreasing as the cells differentiated towards the endothelial cell lineage. Notably, we observed two distinct patterns of γH2AX foci: the typical discrete γH2AX foci, which colocalize with the transcriptionally permissive chromatin mark H3K4me3, and the less well-characterized clustered γH2AX regions, which were only observed in intermediate progenitor cells. Next, we explored responses of mESCs to γ-radiation (137Cs). Following exposure to γ-radiation, mESCs showed a reduction in cell viability and increased γH2AX foci, indicative of radiosensitivity. Despite irradiation, surviving mESCs retained their differentiation potential. To further exemplify our findings, we investigated neural stem progenitor cells (NSPCs). Similar to mESCs, NSPCs displayed clustered γH2AX foci associated with progenitor cells and discrete γH2AX foci indicative of embryonic stem cells or differentiated cells. In conclusion, our findings demonstrate that γH2AX serves as a versatile marker of DSBs and may have a role as a biomarker in stem cell differentiation. The distinct patterns of γH2AX foci in differentiating mESCs and NSPCs provide valuable insights into DNA repair dynamics during differentiation, shedding light on the intricate balance between genomic integrity and cellular plasticity in stem cells. Finally, the clustered γH2AX foci observed in intermediate progenitor cells is an intriguing feature, requiring further exploration.

Bisect offset ratio and cartilaginous sulcus angle are good combined predictors of recurrent patellar dislocation in children and adolescents.

OBJECTIVES: Recurrent patellar dislocation (RPD) is found most commonly in the juvenile population. While risk factors have been well-established in adults, there remains a paucity in radiographical data to define normal and pathoanatomical juvenile cohorts. The objectives of this paper were to elucidate the differences in the patellofemoral joint between RPD and typically developed (TD) juvenile populations, using MRI measurements, and determine the best independent and combined predictors of RPD. METHODS: A prospective, cross-sectional study was conducted with 25 RPD and 24 TD participants aged between 8 and 19 years. MR images were obtained to assess common measures of lower limb alignment, patellofemoral alignment, and trochlear dysplasia. RESULTS: Significant differences were evident for acetabular inclination, tibial-femoral torsion, tibial tubercle-to-trochlear groove (TT-TG) distance, lateral patellar tilt (LPT), cartilaginous sulcus angle (CSA) and bisect offset ratio (BOR). CSA and BOR were included in the final predictive model, which correctly classified 89.4% of RPD cases. CONCLUSION: Radiographical parameters that stratify risk of RPD in adults are also able to predict RPD in the pediatric population (TT-TG, LPT, CSA and BOR). Together, CSA and BOR accurately identified 89.4% of RPD. These measures should be included in the evaluation of pediatric patients who present with patellar dislocation. LEVEL OF EVIDENCE: Level II.