Biology subjects

Arezza, E.

Publications and source records attributed to Arezza, E..

2 recordsLinked to original sources

bioRxiv2024

Caspase-Activated DNase Localizes to Cancer Causing Translocation Breakpoints During Cell Differentiation

Caspase activated DNase (CAD) induced DNA breaks promote cell differentiation and therapy-induced cancer cell resistance. CAD targeting activity is assumed to be unique to each condition, as differentiation and cancer genesis are divergent cell fates. Here, we made the surprising discovery that a subset of CAD-bound targets in differentiating muscle cells are the same genes involved in the genesis of cancer-causing translocations. In muscle cells, a prominent CAD-bound gene pair is Pax7 and Foxo1a, the mismatched reciprocal loci that give rise to alveolar rhabdomyosarcoma. We show that CAD-targeted breaks in the Pax7 gene are physiologic to reduce Pax7 expression, a prerequisite for muscle cell differentiation. A cohort of these CAD gene targets are also conserved in early differentiating T cells and include genes that spur leukemia/lymphoma translocations. Our results suggest the CAD targeting of translocation prone oncogenic genes is non-pathologic biology and aligns with initiation of cell fate transitions.

genomics↗

bioRxiv2023

Self-renewing Sox9+ osteochondral stem cells in the postnatal skeleton

Postnatal skeletal growth, homeostatic maintenance, and regeneration is driven by skeletal stem cells. In addition, it is well established that skeletal tissues lose their regenerative potential with age, comorbidities, and repeated trauma, possibly through stem cell exhaustion or loss of function. However, it is largely unknown where these cells reside in skeletal tissues, what molecular mechanisms regulate their self-renewal and fate decisions, and how to isolate, purify, and expand them ex vivo. Therefore, there is an urgent need for a deeper understanding of postnatal skeletal stem cells. Here, we used genetic lineage tracing, thymidine analogues retention, whole bone microscopy, imaging cytometry, in vitro assays, and single cell transcriptomics and provide the first experimental evidence for the existence of self-renewing osteochondral stem cells in the postnatal skeleton in both males and females. We also show direct comparisons between adult, fetal, mouse, and human skeletal stem cells at the transcriptome level.

developmental biology↗