To counterbalance cellular losses due to age or injury,adult tissues must produce replacement cells appropriate in type and number.In different tissues,evolution has arrived at distinct solutions to this problem,depen...To counterbalance cellular losses due to age or injury,adult tissues must produce replacement cells appropriate in type and number.In different tissues,evolution has arrived at distinct solutions to this problem,depending on the nature of the tissue.Tissues with a large amount of cell turnover,such as the intestine,harbor a dedicated pool of stem cells dedicated to the constant replenishment of lost cells.In contrast,the pancreas is a relatively quiescent organ that lacks a clear population of resident stem cells.Instead,occasional self-duplication appears to be the major form of cellular replacement in the normal pancreas.Upon injury,however,the epigenetic barriers between cell types begin to fall,resulting in cell identity interconversion between multiple cell types in the pancreas.The epigenetic basis for these transdifferentiation events,involves the down-regulation of lineage-determining transcription factors specifying 1 cell fate and their replacement with factors specifying the alternate cell fate.The signals that underpin the switching of transcriptional programs are beginning to be unraveled.One important form of pancreatic plasticity,acinar-to-ductal metaplasia,occurs in response to injury-induced inflammatory stimuli.This form of metaplasia is associated with pancreatitis,a known risk factor for pancreatic cancer.The resulting ductal structures reactivate signaling pathways associated with embryonic pancreatic progenitors,and have been proposed to contribute to pancreatic regeneration.Consistent with a progenitor-like phenotype,in the presence of oncogenic stimuli,these metaplastic ducts are highly sensitive to neoplastic transformation,for reasons that are beginning to come to light.展开更多
文摘To counterbalance cellular losses due to age or injury,adult tissues must produce replacement cells appropriate in type and number.In different tissues,evolution has arrived at distinct solutions to this problem,depending on the nature of the tissue.Tissues with a large amount of cell turnover,such as the intestine,harbor a dedicated pool of stem cells dedicated to the constant replenishment of lost cells.In contrast,the pancreas is a relatively quiescent organ that lacks a clear population of resident stem cells.Instead,occasional self-duplication appears to be the major form of cellular replacement in the normal pancreas.Upon injury,however,the epigenetic barriers between cell types begin to fall,resulting in cell identity interconversion between multiple cell types in the pancreas.The epigenetic basis for these transdifferentiation events,involves the down-regulation of lineage-determining transcription factors specifying 1 cell fate and their replacement with factors specifying the alternate cell fate.The signals that underpin the switching of transcriptional programs are beginning to be unraveled.One important form of pancreatic plasticity,acinar-to-ductal metaplasia,occurs in response to injury-induced inflammatory stimuli.This form of metaplasia is associated with pancreatitis,a known risk factor for pancreatic cancer.The resulting ductal structures reactivate signaling pathways associated with embryonic pancreatic progenitors,and have been proposed to contribute to pancreatic regeneration.Consistent with a progenitor-like phenotype,in the presence of oncogenic stimuli,these metaplastic ducts are highly sensitive to neoplastic transformation,for reasons that are beginning to come to light.
