Administrative Supplement for Combining Experiments and Computer Simulation to Improve the Stem Cell Differentiation Process

摘要 这项工作的总体目标是实验观察干细胞分化，脂肪形成，单细胞， 获得机械生物学随时间变化的更准确模型。高速仿真模型 脂肪形成目前是基于对干细胞培养物的平均总体性质的观察。因为 模型是单细胞的，通过获取更多的细胞数据，可以提高模型的准确性和预测能力。 单细胞的干细胞特性的变化可以随着时间的推移进行跟踪。将开发一个孵化器， 这笔赠款的一部分，以维持干细胞在显微镜下至少15天，这将允许照片， 细胞和核膜形态的规则间隔。然而，许多时间依赖的数据 细胞特性仍然很难获得，因为染色细胞以检查其组成状态的过程， 或用光学镊子探测其性质，通常会杀死细胞。因此，细胞将被牺牲， 15天后，将采用高速模拟的方法进行工作倒推，估算出初始相关性能 成功和不成功的脂肪形成。比较成功和不成功的分化将产生 提供成功脂肪形成的早期指示的生物标志物，如母基金的目标1中所提出的。 这些额外的单个干细胞实验将补充从集合实验获得的数据 在父母补助金中提出。

ABSTRACT The overall goal of this work is to experimentally observe stem cell differentiation, adipogenesis, of single cells to gain a more accurate model of the changes in mechanobiology over time. The high-speed simulation model of adipogenesis is currently based on observations of averaged ensemble properties of stem cell cultures. Because the model is of a single cell, its accuracy and predictive capability can be improved by obtaining more data on the changes in stem cell properties for single cells that can be tracked over time. An incubator will be developed as part of this grant to sustain stem cells under a microscope for at least 15 days, which will allow photographs at regular intervals of the morphology of the cell and nuclear membranes. However, time-dependent data on many cell properties is still difficult to obtain because the process of dyeing the cell to examine the state of its compo- nents, or probing its properties with an optical tweezer, typically kills the cell. Thus, the cells will be sacrificed after 15 days, and the high-speed simulation will be used work backward to estimate the initial properties related to successful and unsuccessful adipogenesis. Comparing successful and unsuccessful differentiation will yield biomarkers that provide early indication of successful adipogenesis, as proposed in Aim 1 of the parent grant. These additional single stem cell experiments will complement the data obtained from the ensemble experiments proposed in the parent grant.