In response to inflammation, pancreatic acinar cells can undergo acinar-to-ductal metaplasia (ADM), a reprogramming event that induces transdifferentiation to a ductlike phenotype and, in the context of additional oncogenic stimulation, contributes to development of pancreatic cancer. The signaling mechanisms underlying pancreatitis-inducing ADM are largely undefined. Our results provide eviden...

Heart disease remains a leading cause of mortality and a major worldwide healthcare burden. Recent advances in stem cell biology have made it feasible to derive large quantities of cardiomyocytes for disease modeling, drug development, and regenerative medicine. The discoveries of reprogramming and transdifferentiation as novel biological processes have significantly contributed to this paradig...

The α and β cells act in concert to maintain blood glucose. The α cells release glucagon in response to low levels of glucose to stimulate glycogenolysis in the liver. In contrast, β cells release insulin in response to elevated levels of glucose to stimulate peripheral glucose disposal. Despite these opposing roles in glucose homeostasis, α and β cells are derived from a common progenitor and ...

The thoracic thymus is the primary vertebrate organ for T-cell generation. Accessory cervical thymi have also been identified in humans and mice, and shown in mice to be independent functional organs that support T-cell development. However, their origin and functional significance remain unclear. Here we show that cervical thymi in mice have following two origins: delayed differentiation of en...

Acinar-to-ductal metaplasia in the pancreas is associated with an increased risk for tumorigenesis. Molecular dissection of this process in vitro has shown that primary acinar cells, in response to EGF receptor ligands, can transdifferentiate into duct-like epithelia, passing through a nestin-positive intermediate, in a Notch pathway-dependent manner. Here, we show that in vitro acinar transdif...

The clinical management of cutaneous melanoma would benefit significantly from a better understanding of the molecular changes that occur during melanocytic progression to a melanoma phenotype. To gain unique insights into this process, we developed a three-dimensional in vitro model that allows observations of normal human melanocytes interacting with a metastatic melanoma matrix to determine ...

Cell therapy means treating diseases with the body's own cells. The ability to produce differentiated cell types at will offers a compelling new approach to cell therapy and therefore for the treatment and cure of a plethora of clinical conditions, including diabetes, Parkinson's disease and cardiovascular disease. Until recently, it was thought that differentiated cells could only be produced ...