At present, however, evaluating the quantitative time courses of cell proliferation in vivo requires enormous efforts and resources, because laborious experiments, including the sacrifice of numerous animals and analyses of the samples at many timepoints, must be performed. To precisely understand the mechanisms underlying these complex processes, information regarding how cell proliferative responses change over time is important. Cell proliferative processes play pivotal roles in adapting to many biological situations, such as tissue repair and augmenting the amount of tissue in response to increased systemic demand. To maintain homeostasis, cells proliferate dynamically according to changing endogenous and exogenous conditions. Thus, these technologies may contribute to advancements in broad areas of biological and medical research. Moreover, this strategy can be utilized for highly sensitive ex vivo screening for proliferative factors for targeted cells. Physiological time courses, during obesity development, pregnancy and juvenile growth, as well as diurnal variation, of β-cell proliferation, are clearly detected. Crossing these with tissue-specific Cre-expressing mice allows us to monitor the proliferation time course of pancreatic β-cells, which are few in number and weakly proliferative, by measuring plasma luciferase activity. We generate mice expressing a secreted type of luciferase only in cells producing Cre under the control of the Ki67 promoter. Herein, we establish a highly sensitive and simple strategy by which time-series showing the proliferation of a targeted cell type can be quantitatively monitored in vivo in the same individuals. Cell proliferation processes play pivotal roles in timely adaptation to many biological situations.
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