Search

Centromeres ensure faithful chromosome partition upon cell division. This work reveals a novel role for centromeres in establishing/maintaining stem cell identity. Centromeric proteins are asymmetrically incorporated on sister chromatids before asymmetric division of Drosophila germline stem cells, which allows for selective chromosome segregation., Centromeres are epigenetically defined by CENP-A–containing chromatin and are essential for cell division. Previous studies suggest asymmetric inheritance of centromeric proteins upon stem cell division; however, the mechanism and implications of selective chromosome segregation remain unexplored. We show that Drosophila female germline stem cells (GSCs) and neuroblasts assemble centromeres after replication and before segregation. Specifically, CENP-A deposition is promoted by CYCLIN A, while excessive CENP-A deposition is prevented by CYCLIN B, through the HASPIN kinase. Furthermore, chromosomes inherited by GSCs incorporate more CENP-A, making stronger kinetochores that capture more spindle microtubules and bias segregation. Importantly, symmetric incorporation of CENP-A on sister chromatids via HASPIN knockdown or overexpression of CENP-A, either alone or together with its assembly factor CAL1, drives stem cell self-renewal. Finally, continued CENP-A assembly in differentiated cells is nonessential for egg development. Our work shows that centromere assembly epigenetically drives GSC maintenance and occurs before oocyte meiosis.

Introduction: Pulmonary regurgitation is common following tetralogy of Fallot (TOF) repair and leads to progressive right ventricular (RV) dilatation and dysfunction. There is limited data on ventricular remodeling and adaption following surgical pulmonary valve replacement (PVR), especially beyond the short-term. Hypothesis: Our objective is to assess medium-term effects of PVR on right ventricular mechanics in patients with surgically repaired TOF. Methods: Speckle-tracking echocardiography was performed on pre-operative and post-operative echocardiograms in 50 patients with repaired TOF who underwent surgical PVR. RV global and segmental myocardial deformation parameters were assessed. Transthoracic studies 2.1±2.1 months pre-PVR, 2.23±0.61 months post-PVR (early follow-up) and 14.9±3.8 months post-PVR (medium-term follow-up) were analyzed. Results: The mean age at PVR was 12.6±3.3 years. Global RV longitudinal strain fell from -19.2%±2.7% to -16.8%±2.6% at early follow-up (p Conclusion: Although an early reduction in RV longitudinal strain occurs following PVR, the volume unloading effects of PVR has a significant effect on late RV remodelling as reflected by improvements in global RV longitudinal, basal and mid segmental strain late post-PVR. The effects of reversed remodelling of the RV may have important clinical implications towards determining the optimal timing of PVR in this subset of patients.