title: System-wide analysis of the transcriptional network of human myelomonocytic leukemia cells predicts attractor structure and phorbol-ester-induced differentiation and dedifferentiation transitions.
abstract: We present a system-wide transcriptional network structure that controls cell types in the context of expression pattern transitions that correspond to cell type transitions. Co-expression based analyses uncovered a system-wide, ladder-like transcription factor cluster structure composed of nearly 1,600 transcription factors in a human transcriptional network. Computer simulations based on a transcriptional regulatory model deduced from the system-wide, ladder-like transcription factor cluster structure reproduced expression pattern transitions when human THP-1 myelomonocytic leukaemia cells cease proliferation and differentiate under phorbol myristate acetate stimulation. The behaviour of MYC, a reprogramming Yamanaka factor that was suggested to be essential for induced pluripotent stem cells during dedifferentiation, could be interpreted based on the transcriptional regulation predicted by the system-wide, ladder-like transcription factor cluster structure. This study introduces a novel system-wide structure to transcriptional networks that provides new insights into network topology.
authors: 1] National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-city, Chiba 263-8555, Japan [2] Maebashi Institute of Technology, 460-1 Kamisadori-machi, Maebashi-city, Gunma 371-0816, Japan.
authors: Katsumi
authors: K
authors: Sakata
authors: 1] National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-city, Chiba 263-8555, Japan [2] Maebashi Institute of Technology, 460-1 Kamisadori-machi, Maebashi-city, Gunma 371-0816, Japan [3] Mitsubishi Space Software Co., Ltd., Tsukuba-Mitsui Building, 1-6-1 Takezono, Tsukuba-city, Ibaraki 305-0032, Japan [4] National Institute of Genetics, 1111 Yata, Mishima-city, Shizuoka 411-8540, Japan.
authors: Hajime
authors: H
authors: Ohyanagi
authors: Maze Inc., 1-2-17 M604, Sennin-machi, Hachioji-city, Tokyo 193-0835, Japan.
authors: Shinji
authors: S
authors: Sato
authors: Mitsubishi Space Software Co., Ltd., Tsukuba-Mitsui Building, 1-6-1 Takezono, Tsukuba-city, Ibaraki 305-0032, Japan.
authors: Hiroya
authors: H
authors: Nobori
authors: National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-city, Chiba 263-8555, Japan.
authors: Akiko
authors: A
authors: Hayashi
authors: 1] National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-city, Chiba 263-8555, Japan [2] Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita-city, Osaka 565-0871, Japan.
authors: Hideshi
authors: H
authors: Ishii
authors: 1] RIKEN Omics Science Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama-city, Kanagawa, 230-0045, Japan [2] RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama-city, Kanagawa, 230-0045, Japan [3] Department of Biosciences and Nutrition and Science for Life Laboratory, Karolinska Institutet, Stockholm, SE-141 86, Sweden.
authors: Carsten O
authors: CO
authors: Daub
authors: 1] RIKEN Omics Science Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama-city, Kanagawa, 230-0045, Japan [2] RIKEN Preventive Medicine and Diagnosis Innovative Program, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors: Jun
authors: J
authors: Kawai
authors: 1] RIKEN Omics Science Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama-city, Kanagawa, 230-0045, Japan [2] RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama-city, Kanagawa, 230-0045, Japan.
authors: Harukazu
authors: H
authors: Suzuki
authors: National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-city, Chiba 263-8555, Japan.
authors: Toshiyuki
authors: T
authors: Saito
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D015973:Gene Expression Regulation, Leukemic; D053263:Gene Regulatory Networks; D006801:Humans; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics* / Q000473:pathology*; D008954:Models, Biological; D010703:Phorbol Esters / Q000494:pharmacology*; D014158:Transcription, Genetic
chemical_list: D010703:Phorbol Esters
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