Median raphe cyst: A clinically challenging diagnosis.

Median raphe cyst is an uncommon developmental anomaly that can develop anywhere along the midline of the external genitals. Only a few hundred cases have been published in the English literature and the lack of awareness of this entity can lead to confusion and misdiagnosis. We report here a case of median raphe cyst located in the midline of the anterior scrotum of a 35- year-old man. Clinically, the patient presented with a scrotal mass increasing substantially in size over two days associated with tenderness, skin erythema, and scrotal pain. Radiologic interpretation of a sonogram and computed tomography scan suggested a thrombosed vessel. The patient was diagnosed with septic thrombophlebitis associated with overlying cellulitis. Despite conservative therapy with antibiotics, the patient developed pyrexia, tachycardia, and leukocytosis prompting surgical excision of the lesion. Histopathologic examination revealed an infected median raphe cyst. The cyst wall was lined by a stratified epithelium that included numerous Alcian blue positive goblet cells. The epithelial cells showed reactive changes with infiltration by numerous neutrophils. Our objective is to bring attention to and thereby facilitate the diagnosis of this unusual entity.

Smek1/2 is a nuclear chaperone and cofactor for cleaved Wnt receptor Ryk, regulating cortical neurogenesis.

The receptor-like tyrosine kinase (Ryk), a Wnt receptor, is important for cell fate determination during corticogenesis. During neuronal differentiation, the Ryk intracellular domain (ICD) is cleaved. Cleavage of Ryk and nuclear translocation of Ryk-ICD are required for neuronal differentiation. However, the mechanism of translocation and how it regulates neuronal differentiation remain unclear. Here, we identified Smek1 and Smek2 as Ryk-ICD partners that regulate its nuclear localization and function together with Ryk-ICD in the nucleus through chromatin recruitment and gene transcription regulation. Smek1/2 double knockout mice displayed pronounced defects in the production of cortical neurons, especially interneurons, while the neural stem cell population increased. In addition, both Smek and Ryk-ICD bound to the Dlx1/2 intergenic regulator element and were involved in its transcriptional regulation. These findings demonstrate a mechanism of the Ryk signaling pathway in which Smek1/2 and Ryk-ICD work together to mediate neural cell fate during corticogenesis.

Neural Crest Cell Implantation Restores Enteric Nervous System Function and Alters the Gastrointestinal Transcriptome in Human Tissue-Engineered Small Intestine.

Acquired or congenital disruption in enteric nervous system (ENS) development or function can lead to significant mechanical dysmotility. ENS restoration through cellular transplantation may provide a cure for enteric neuropathies. We have previously generated human pluripotent stem cell (hPSC)-derived tissue-engineered small intestine (TESI) from human intestinal organoids (HIOs). However, HIO-TESI fails to develop an ENS. The purpose of our study is to restore ENS components derived exclusively from hPSCs in HIO-TESI. hPSC-derived enteric neural crest cell (ENCC) supplementation of HIO-TESI establishes submucosal and myenteric ganglia, repopulates various subclasses of neurons, and restores neuroepithelial connections and neuron-dependent contractility and relaxation in ENCC-HIO-TESI. RNA sequencing identified differentially expressed genes involved in neurogenesis, gliogenesis, gastrointestinal tract development, and differentiated epithelial cell types when ENS elements are restored during in vivo development of HIO-TESI. Our findings validate an effective approach to restoring hPSC-derived ENS components in HIO-TESI and may implicate their potential for the treatment of enteric neuropathies.