标题： 拓扑结构、动力学与克隆骨髓基质细胞群的遗传特性 显示英文标题

标题： Topology, Kinetics and Inheritance in Clonal Colonies of Bone Marrow Stromal Cells

摘要： 骨髓间充质细胞（BMSCs）的群体包含具有相关治疗应用的多潜能骨骼干细胞，在体外培养时会产生非常异质的集落，这一特性可能会严重阻碍基于BMSC的疗法的临床应用。因此，更好地了解这种异质性的本质以及决定它的因素是非常重要的。 在这里，我们通过使用延时显微镜研究了来自六个供体的N=28个人类BMSC集落的结构，每个集落来源于一个单细胞，并追踪它们的谱系树直至第七代。 我们证实了在谱系的拓扑结构和集落的复制动力学中存在非常显著的集落间和集落内异质性。 我们还发现拓扑结构和动力学之间存在强烈的相关性，这与调节因子的存在一致，这些调节因子连接着不活跃细胞的亚群，它唯一决定了谱系的拓扑结构，以及活跃细胞的亚群，它们是集落增殖率的唯一负责人。 最后，我们对每个集落进行了基于熵的遗传性测试，该测试测量了同一谱系分支内不活跃细胞的非随机聚集程度，发现在大多数实验谱系中，不活跃细胞出现概率的遗传传递有明显的特征。 显示英文摘要

摘要： Bone marrow stromal cells (BMSCs), whose populations contain multipotent skeletal stem cells with relevant therapeutic applications, are known to produce very heterogeneous colonies upon in vitro culture, a trait that may severely hinder the clinical usefulness of BMSC-based therapies. Therefore, reaching a better insight on the nature of such heterogeneity, as well as on the factors determining it, is important. Here, by using time-lapse microscopy, we study the structure of N=28 human BMSC colonies from six donors, each colony derived from a single cell, and trace their lineage trees up to the seventh generation. We confirm the presence of very significant inter-colony and intra-colony heterogeneities, both in the topology of the lineages and in the replicative kinetics of the colonies. We also find that topology and kinetics are strongly correlated, consistent with the existence of regulating factors linking the sub-population of inactive cells, which uniquely determine a lineage's topology, and that of active cells, which are the sole responsible for the proliferation rate of the colony. Finally, we submit each colony to an entropy-based inheritance test, which measures the degree of non-random clustering of inactive cells within the same branches of the lineage, and find a clear signature of hereditary transmission of the probability of emergence of inactive cells in the largest majority of the experimental lineages.