all β cells contribute equally to islet growth and maintenance所有同样有助于胰岛β细胞增长和维护.pdfVIP

PLoS BIOLOGY All b Cells Contribute Equally to Islet Growth and Maintenance Kristen Brennand1,2,3, Danwei Huangfu1,2,3, Doug Melton1,2,3* 1 Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, United States of America, 2 Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, United States of America, 3 Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, United States of America In healthy adult mice, the b cell population is not maintained by stem cells but instead by the replication of differentiated b cells. It is not known, however, whether all b cells contribute equally to growth and maintenance, as it may be that some cells replicate while others do not. Understanding precisely which cells are responsible for b cell replication will inform attempts to expand b cells in vitro, a potential source for cell replacement therapy to treat diabetes. Two experiments were performed to address this issue. First, the level of fluorescence generated by a pulse of histone 2B–green fluorescent protein (H2BGFP) expression was followed over time to determine how this marker is diluted with cell division; a uniform loss of label across the entire b cell population was observed. Second, clonal analysis of dividing b cells was completed; all clones were of comparable size. These results support the conclusion that the b cell pool is homogeneous with respect to replicative capacity and suggest that all b cells are candidates for in vitro expansion. Given similar observations in the hepatocyte population, we speculate that for tissues lacking an adult stem cell, they are replenished equally by replication of all differentiated cells. Citation: Brennand K, Huangfu