基于布尔网络的造血细胞谱系分化选择分析

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摘要:

造血干细胞通过分化获得不同的成熟血细胞类型以满足不同的生理需求.通过整合两个已有的基因调控网络并进行修正,构建了综合调控网络以及对应的逻辑模型,可以更全面地反映不同基因在造血干细胞分化过程中的作用.该网络的稳态结果包含了两个小网络中涉及的大部分细胞类型,与实际的ChIP-seq数据结果一致.对综合调控网络进行瞬态扰动与持续扰动,分析了6种主要细胞类型之间正常分化所需要的最简扰动策略.获得的整合调控网络与逻辑模型可以为理解造血干细胞的分化特异性选择提供一些定性的参考依据,同时分析得到的扰动策略可以为实际的细胞培养实验提供一些方案上的建议.

Mature hematopoietic stem cells can differentiate into different blood cell types.By integrating two reported gene networks and incorporating more regulatory information,we construct a comprehensive regulatory network related to hematopoietic stem cells.Furthermore,a qualitative systems-level logical model is presented to understand the mechanism of cell specification with different genes.In agreement with ChIP-seq data,steady states predicted by the model correspond to terminally differentiated cell types,which includes most of cell types in the two subnetworks.Next,we explore possible mechanisms of how each lineage differentiation is realized by two kinds of systematic perturbations,i.e.,transient and persistent perturbations.Two kinds of perturbations give rise to the same results,indicating the robustness of the integrated network and logical model.The integrated network and the logical model presented here might be a good candidate for providing qualitative mechanisms of cell fate specification involved in hematopoietic stem cells.The identified perturbation strategies can also provide some suggestion about choosing perturbation targets for further experimental analysis.

作者:

王瑞琦陈庆曦叶坚挺

Wang Ruiqi;Chen Qingxi;Ye Jianting(College of Sciences,Shanghai University,Shanghai 200444,China)

机构地区:

上海大学理学院

出处:

《betway官方app 学报：自然科学版》 CAS 北大核心 2022年第3期59-66,共8页

Journal of Henan Normal University(Natural Science Edition)

基金:

国家自然科学基金(11971297)。

关键词:

造血系统基因调控网络布尔网络扰动分析