Stem cell homeostasis regulated by hierarchy and neutral competition

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  • Nakamuta, Asahi
    Laboratory of Theoretical Biology, Graduate School of Biostudies, Kyoto University; Faculty of Science, Kyoto University
  • Yoshido, Kana
    Laboratory of Theoretical Biology, Graduate School of Biostudies, Kyoto University
  • Naoki, Honda
    Laboratory of Theoretical Biology, Graduate School of Biostudies, Kyoto University; Laboratory of Data-driven Biology, Graduate School of Integrated Sciences for Life, Hiroshima University; Kansei-Brain Informatics Group, Center for Brain, Mind and Kansei Sciences Research (BMK Center), Hiroshima University; Theoretical Biology Research Group, Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences
  • 中牟田, 旭
  • 吉戸, 香奈
  • 本田, 直樹

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Tissue stem cells maintain themselves through self-renewal while constantly supplying differentiating cells. Two distinct models have been proposed as mechanisms of stem cell homeostasis. According to the classical model, there is hierarchy among stem cells, and master stem cells produce stem cells by asymmetric division; whereas, according to the recent model, stem cells are equipotent and neutrally compete. However, the mechanism remains controversial in several tissues and species. Here, we developed a mathematical model linking the two models, named the hierarchical neutral competition (hNC) model. Our theoretical analysis showed that the combination of the hierarchy and neutral competition exhibited bursts in clonal expansion, which was consistent with experimental data of rhesus macaque hematopoiesis. Furthermore, the scaling law in clone size distribution, considered a unique characteristic of the recent model, was satisfied even in the hNC model. Based on the findings above, we proposed the criterion for distinguishing the three models based on experiments.

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