Cellular reprogramming in vivo initiated by SOX4 pioneer factor activity.

Tissue damage elicits cell fate switching through a process called metaplasia, but how the starting cell fate is silenced and the new cell fate is activated has not been investigated in animals. In cell culture, pioneer transcription factors mediate "reprogramming" by opening new chromatin sites for expression that can attract transcription factors from the starting cell's enhancers. Here we report that SOX4 is sufficient to initiate hepatobiliary metaplasia in the adult mouse liver, closely mimicking metaplasia initiated by toxic damage to the liver. In lineage-traced cells, we assessed the timing of SOX4-mediated opening of enhancer chromatin versus enhancer decommissioning. Initially, SOX4 directly binds to and closes hepatocyte regulatory sequences via an overlapping motif with HNF4A, a hepatocyte master regulatory transcription factor. Subsequently, SOX4 exerts pioneer factor activity to open biliary regulatory sequences. The results delineate a hierarchy by which gene networks become reprogrammed under physiological conditions, providing deeper insight into the basis for cell fate transitions in animals.

Physiological reprogramming in vivo mediated by Sox4 pioneer factor activity.

Tissue damage elicits cell fate switching through a process called metaplasia, but how the starting cell fate is silenced and the new cell fate is activated has not been investigated in animals. In cell culture, pioneer transcription factors mediate "reprogramming" by opening new chromatin sites for expression that can attract transcription factors from the starting cell's enhancers. Here we report that Sox4 is sufficient to initiate hepatobiliary metaplasia in the adult liver. In lineage-traced cells, we assessed the timing of Sox4-mediated opening of enhancer chromatin versus enhancer decommissioning. Initially, Sox4 directly binds to and closes hepatocyte regulatory sequences via a motif it overlaps with Hnf4a, a hepatocyte master regulator. Subsequently, Sox4 exerts pioneer factor activity to open biliary regulatory sequences. The results delineate a hierarchy by which gene networks become reprogrammed under physiological conditions, providing deeper insight into the basis for cell fate transitions in animals.

Rapid in vivo multiplexed editing (RIME) of the adult mouse liver.

BACKGROUND AND AIMS: Assessing mammalian gene function in vivo has traditionally relied on manipulation of the mouse genome in embryonic stem cells or perizygotic embryos. These approaches are time-consuming and require extensive breeding when simultaneous mutations in multiple genes is desired. The aim of this study is to introduce a rapid in vivo multiplexed editing (RIME) method and provide proof of concept of this system. APPROACH AND RESULTS: RIME, a system wherein CRISPR/caspase 9 technology, paired with adeno-associated viruses (AAVs), permits the inactivation of one or more genes in the adult mouse liver. The method is quick, requiring as little as 1 month from conceptualization to knockout, and highly efficient, enabling editing in >95% of target cells. To highlight its use, we used this system to inactivate, alone or in combination, genes with functions spanning metabolism, mitosis, mitochondrial maintenance, and cell proliferation. CONCLUSIONS: RIME enables the rapid, efficient, and inexpensive analysis of multiple genes in the mouse liver in vivo .

Emergency laparoscopic resection of the anterior rectum due to rectal trauma secondary to compressed air, case report.

In the XIX century, the surgeon faces surgical challenges due to the creation of new technologies. Accidental or compressed air-induced injury to the colon and rectum is rare. We present the case of a 45-year-old patient who consults the emergency department, then a high-pressure rectal pneumatic trauma, with clinical findings of peritonism, managed with a Hartmann-type colostomy. and anterior resection of the rectum using laparoscopy, with findings of rectosigmoid perforation. With this, it can be demonstrated that minimally invasive surgery is a feasible approach in hemodynamically unstable patients without contraindication for pneumoperitoneum.

Laparoscopic management of gastric liposarcoma: A case report and review of the literature.

INTRODUCTION: Liposarcoma is one of the most common mesenchymal neoplasms in adults. Predominant locations are the retroperitoneum and limbs, it rarely occurs in the gastrointestinal tract. Gastric liposarcoma is extremely rare, with fewer than 30 cases reported around the world. PRESENTATION OF CASE: Here we present the case of a 70-year-old female patient who was diagnosed with gastric liposarcoma and managed with laparoscopic surgical resection. The patient is currently being followed up and is alive without recurrence 12 months after the operation. DISCUSSION: Gastric liposarcoma approach requires proper diagnosis with computed tomography and endoscopy, in order to develop an adequate surgical plan. Laparoscopic en-bloc resection and gastrointestinal reconstruction is the ideal management in this type of patient. CONCLUSION: Gastric liposarcoma is an extremely rare entity, his management consists of wide en-bloc resection with a gastrointestinal reconstruction.