All beta cells contribute equally to islet growth and maintenance.
In healthy adult mice, the beta cell population is not maintained by stem cells but instead by the replication of differentiated beta cells. It is not known, however, whether all beta 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 beta cell replication will inform attempts to expand beta 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 beta cell population was observed. Second, clonal analysis of dividing beta cells was completed; all clones were of comparable size. These results support the conclusion that the beta cell pool is homogeneous with respect to replicative capacity and suggest that all beta 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.
Brennand
Kristen
K
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, United States of America.
Huangfu
Danwei
D
Melton
Doug
D
D053687:Adult Stem Cells / Q000166:cytology; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D017930:Genes, Reporter; D005819:Genetic Markers; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009030:Mosaicism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013752:Tetracycline
D005819:Genetic Markers; D006657:Histones; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D013752:Tetracycline