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造血作用的动态自组织与(非)对称细胞分裂。

Dynamic self-organisation of haematopoiesis and (a)symmetric cell division.

作者信息

Måløy Marthe, Måløy Frode, Jakobsen Per, Olav Brandsdal Bjørn

机构信息

Department of Mathematics and Statistics, University of Tromsø, Norway.

Department of Mathematics and Statistics, University of Tromsø, Norway.

出版信息

J Theor Biol. 2017 Feb 7;414:147-164. doi: 10.1016/j.jtbi.2016.11.030. Epub 2016 Dec 5.

Abstract

A model of haematopoiesis that links self-organisation with symmetric and asymmetric cell division is presented in this paper. It is assumed that all cell divisions are completely random events, and that the daughter cells resulting from symmetric and asymmetric stem cell divisions are, in general, phenotypically identical, and still, the haematopoietic system has the flexibility to self-renew, produce mature cells by differentiation, and regenerate undifferentiated and differentiated cells when necessary, due to self-organisation. As far as we know, no previous model implements symmetric and asymmetric division as the result of self-organisation. The model presented in this paper is inspired by experiments on the Drosophila germline stem cell, which imply that under normal conditions, the stem cells typically divide asymmetrically, whereas during regeneration, the rate of symmetric division increases. Moreover, the model can reproduce several of the results from experiments on female Safari cats. In particular, the model can explain why significant fluctuation in the phenotypes of haematopoietic cells was observed in some cats, when the haematopoietic system had reached normal population level after regeneration. To our knowledge, no previous model of haematopoiesis in Safari cats has captured this phenomenon.

摘要

本文提出了一种将自我组织与对称和不对称细胞分裂联系起来的造血模型。假定所有细胞分裂均为完全随机事件,并且对称和不对称干细胞分裂产生的子细胞通常在表型上是相同的,然而,由于自我组织,造血系统仍具有自我更新的灵活性,能够通过分化产生成熟细胞,并在必要时再生未分化和已分化的细胞。据我们所知,以前没有模型将对称和不对称分裂作为自我组织的结果来实现。本文提出的模型受到果蝇生殖系干细胞实验的启发,这些实验表明,在正常情况下,干细胞通常进行不对称分裂,而在再生过程中,对称分裂的速率会增加。此外,该模型能够重现雌性萨凡纳猫实验的若干结果。特别是,该模型可以解释为什么在一些猫中,当造血系统在再生后达到正常种群水平时,会观察到造血细胞表型的显著波动。据我们所知,以前没有萨凡纳猫造血模型能够捕捉到这一现象。

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