Generation of functionally distinct hemogenic endothelial cell populations from pluripotent stem cells.

A diverse array of protocols have been established for the directed differentiation of human pluripotent stem cells (hPSCs) into a variety of cell types, including blood cells, for modeling development and disease, and for the development of cell-based therapeutics. These protocols recapitulate various signaling requirements essential for the establishment of the hematopoietic systems during embryonic development. However, in many instances, the functional properties of those progenitors, and their relevance to human development, remains unclear.

Depletion of the membrane-fusion regulator Munc18c attenuates caerulein hyperstimulation-induced pancreatitis.

Epithelial pancreatic acinar cells perform crucial functions in food digestion, and acinar cell homeostasis required for secretion of digestive enzymes relies on SNARE-mediated exocytosis. The ubiquitously expressed Sec1/Munc18 protein mammalian uncoordinated-18c (Munc18c) regulates membrane fusion by activating syntaxin-4 (STX-4) to bind cognate SNARE proteins to form a SNARE complex that mediates exocytosis in many cell types. However, in the acinar cell, Munc18c's functions in exocytosis and homeostasis remain inconclusive.

ATM regulates 3-methylpurine-DNA glycosylase and promotes therapeutic resistance to alkylating agents.

Unlabelled: Alkylating agents are a first-line therapy for the treatment of several aggressive cancers, including pediatric glioblastoma, a lethal tumor in children. Unfortunately, many tumors are resistant to this therapy. We sought to identify ways of sensitizing tumor cells to alkylating agents while leaving normal cells unharmed, increasing therapeutic response while minimizing toxicity.

Effects of ethanol metabolites on exocytosis of pancreatic acinar cells in rats.

Background & Aims: During development of alcoholic pancreatitis, oxidative (acetaldehyde) and nonoxidative metabolites (ethyl palmitate, ethyl oleate), rather than ethanol itself, mediate toxic injury. Exposure of pancreatic acini to ethanol blocks cholecystokinin (CCK)-8-stimulated apical exocytosis and redirects exocytosis to the basolateral plasma membrane, causing interstitial pancreatitis. We examined how each ethanol metabolite contributes to these changes in exocytosis.

Live pancreatic acinar imaging of exocytosis using syncollin-pHluorin.

In this report, a novel live acinar exocytosis imaging technique is described. An adenovirus was engineered, encoding for an endogenous zymogen granule (ZG) protein (syncollin) fused to pHluorin, a pH-dependent green fluorescent protein (GFP). Short-term culture of mouse acini infected with this virus permits exogenous adenoviral protein expression while retaining acinar secretory competence and cell polarity.