King's College London
ORCID: 0000-0002-1527-4683Publishes on Transplantation: Methods and Outcomes, Mechanical Circulatory Support Devices, Pancreatic function and diabetes. 9 papers and 545 citations.
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Ductal cells have been proposed as a source of adult β cell neogenesis, but this has remained controversial. By combining lineage tracing, 3D imaging, and single-cell RNA sequencing (scRNA-seq) approaches, we show that ductal cells contribute to the β cell population over time. Lineage tracing using the Neurogenin3 (Ngn3)-CreERT line identified ductal cells expressing the endocrine master transcription factor Ngn3 that were positive for the δ cell marker somatostatin and occasionally co-expressed insulin. The number of hormone-expressing ductal cells was increased in Akita+/− diabetic mice, and ngn3 heterozygosity accelerated diabetes onset. scRNA-seq of Ngn3 lineage-traced islet cells indicated that duct-derived somatostatin-expressing cells, some of which retained expression of ductal markers, gave rise to β cells. This study identified Ngn3-expressing ductal cells as a source of adult β cell neogenesis in homeostasis and diabetes, suggesting that this mechanism, in addition to β cell proliferation, maintains the adult islet β cell population.
MARZONI, FRANCIS A. M.D.; UPCHURCH, SAMUEL E. M.D.; LAMBERT, C J M.D. Author Information
Most splenic artery aneurysms (SAAs) are asymptomatic at the time of discovery, being found incidentally during laparotomy or angiography. SAAs are most likely to be found in multiparous women. Complications of SAAs include free intraperitoneal rupture and erosion into abdominal viscera or vessels, with resultant high mortality. Surgery is indicated for symptomatic, enlarging, or large (greater than or equal to 2.5 cm) SAAs as well as any SAA found in women of childbearing age. Treatment of such aneurysms depends on the location and includes excision, ligation, and splenectomy. The present report presents the first known case, to our knowledge, of SAA presenting with massive upper gastrointestinal bleeding from erosion into the stomach in a nulliparous woman. Prompt surgical intervention resulted in correct diagnosis and patient survival.