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Energy landscape decomposition for cell differentiation with proliferation effect

查看全文 作　　者：Jifan [1,2]Shi;Kazuyuki [2]Aihara;Tiejun [3]Li;Luonan [4,5,6,7]Chen 高影响力作者 机构地区：[1]Research Institute of Intelligent Complex Systems,Fudan University,Shanghai 200433,China;[2]International Research Center for Neurointelligence,The University of Tokyo Institutes for Advanced Study,The University of Tokyo,Tokyo 113-0033,Japan;[3]Key Laboratory of Mathematics and Its Applications(LMAM)and School of Mathematical Sciences,Peking University,Beijing 100871,China;[4]Key Laboratory of Systems Biology.Shanghai Institute of Biochemistry and Cell Biology,Center for Excellence in Molecular Cell Science,Chinese Academy of Sciences,Shanghai 200031,China;[5]Key Laboratory of Systems Health Science of Zhejiang Province,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Hangzhou 310024,China;[6]School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China;[7]Guangdong Institute of Intelligence Science and Technology,Zhuhai 519031,China高影响力机构 出　　处：《National Science Review》索引2022年第9卷第8期,共9页高影响力期刊 基　　金：This work was supported by the Japan Science and Technology Agency Moonshot R&D(JPMJMS2021);the Japan Agency for Medical Research and Development(JP21dm0307009);the Japan Society for the Promotion of Science KAKENHI(JP20H05921);the Institute of AI and Beyond,The University of Tokyo;upported by the National Key R&D Program of China(2017YFA0505500);the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB38040400);the National Natural Science Foundation of China(11825102,12131020,31930022 and 12026608);the Beijing Academy of Artificial Intelligence(BAAI);the Special Fund for Science and Technology Innovation Strategy of Guangdong Province(2021B0909050004 and 2021B0909060002);the Major Key Project of Peng Cheng Laboratory(PCL2021A12)。 摘　　要：Complex interactions between genes determine the development and differentiation of cells.We establish a landscape theory for cell differentiation with proliferation effect,in which the developmental process is modeled as a stochastic dynamical system with a birth-death term.We find that two different energy landscapes,denoted U and V,collectively contribute to the establishment of non-equilibrium steady differentiation.The potential U is known as the energy landscape leading to the steady distribution,whose metastable states stand for cell types,while V indicates the differentiation direction from pluripotent to differentiated cells.This interpretation of cell differentiation is different from the previous landscape theory without the proliferation effect.We propose feasible numerical methods and a mean-field approximation for constructing landscapes U and V.Successful applications to typical biological models demonstrate the energy landscape decomposition’s validity and reveal biological insights into the considered processes. 关 键 词：energy landscape cell differentiation stochastic systems
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