Werner Benjamin, Beier Fabian, Hummel Sebastian, Balabanov Stefan, Lassay Lisa, Orlikowsky Thorsten, Dingli David, Brümmendorf Tim H, Traulsen Arne
Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany.
Department of Hematology and Oncology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen, Germany.
Elife. 2015 Oct 15;4:e08687. doi: 10.7554/eLife.08687.
We investigate the in vivo patterns of stem cell divisions in the human hematopoietic system throughout life. In particular, we analyze the shape of telomere length distributions underlying stem cell behavior within individuals. Our mathematical model shows that these distributions contain a fingerprint of the progressive telomere loss and the fraction of symmetric cell proliferations. Our predictions are tested against measured telomere length distributions in humans across all ages, collected from lymphocyte and granulocyte sorted telomere length data of 356 healthy individuals, including 47 cord blood and 28 bone marrow samples. We find an increasing stem cell pool during childhood and adolescence and an approximately maintained stem cell population in adults. Furthermore, our method is able to detect individual differences from a single tissue sample, i.e. a single snapshot. Prospectively, this allows us to compare cell proliferation between individuals and identify abnormal stem cell dynamics, which affects the risk of stem cell related diseases.
我们研究了人类造血系统中干细胞在一生中的体内分裂模式。特别是，我们分析了个体内干细胞行为背后端粒长度分布的形状。我们的数学模型表明，这些分布包含了端粒渐进性丢失和对称细胞增殖比例的特征。我们根据从356名健康个体（包括47份脐带血和28份骨髓样本）的淋巴细胞和粒细胞分选端粒长度数据中收集到的所有年龄段人类的端粒长度测量分布，对我们的预测进行了检验。我们发现儿童期和青春期干细胞池在增加，而成年人的干细胞群体大致保持稳定。此外，我们的方法能够从单个组织样本（即单个快照）中检测个体差异。前瞻性地看，这使我们能够比较个体之间的细胞增殖，并识别异常的干细胞动态，而这会影响干细胞相关疾病的风险。
