Development of quantitative cell-phenotyping technology by integrating image-analysis, machine learning and single-cell omics

• Project/Area Number: 18K19312
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: ABE KUNIYA 国立研究開発法人理化学研究所, バイオリソース研究センター, チームリーダー (40240915)
• Project Period (FY): 2018-06-29 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 画像処理・機械学習 / １細胞遺伝子発現解析 / iPS細胞 / ゲノム再プログラム化 / 画像処理 / 機械学習 / 細胞状態 / 再プログラム化 / シングルセル解析 / 細胞表現型 / ヒトiPS細胞 / 定量解析 / シングルセル / ヒトiPS

Outline of Final Research Achievements

In this study, we established a technology for detecting and quantifying various cell types and cell states in a cell population by combining image analysis and machine learning based on microscope images. Combined with comprehensive gene expression analysis at the single-cell level, we have established a technology to quantitatively describe "cellular phenotypes”. By applying this technology to the analysis of the iPS cell formation process, we succeeded in obtaining novel insights into the early process of genome reprogramming.

Academic Significance and Societal Importance of the Research Achievements

本申請では、モデル実験として、iPS細胞について述べたが、iPS形成過程の再プログラム化現象を1細胞レベルで詳細に解析した例は国内外に無く、それ自身非常に科学的価値の高い知見が得られる可能性がある。この技術を元にした細胞診断システムができれば、iPS細胞にとどまらず、幹細胞およびその分化細胞の診断や、すべての細胞リソースの標準化、品質管理に資することとなり、細胞画像取得、画像解析プログラム、データベース構築・運用、細胞リソース提供などをパッケージ化し、実用化していくことも可能と思われる。

Research Products

• [Int'l Joint Research] 台湾 中原大学(その他の国・地域)
• [Journal Article] Human iPS cell-derived cartilaginous tissue spatially and functionally replaces nucleus pulposus (2022)
  • Author(s): Kamatani Takashi、Hagizawa Hiroki、Yarimitsu Seido、Morioka Miho、Koyamatsu Saeko、Sugimoto Michihiko、Kodama Joe、Yamane Junko、Ishiguro Hiroyuki、Shichino Shigeyuki、Abe Kuniya、Fujibuchi Wataru、Fujie Hiromichi、Kaito Takashi、Tsumaki Noriyuki
  • Journal Title: Biomaterials Volume: 284 Pages: 121491-121491
  • DOI: 10.1016/j.biomaterials.2022.121491
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High Resolution U-Net for Quantitatively Analyzing Early Spatial Patterning of Human Induced Pluripotent Stem Cells on Micropatterns (2021)
  • Author(s): Chu Slo-Li、Abe Kuniya、Yokota Hideo、Cho Dooseon、Chen Yuan-Hao、Tsai Ming-Dar
  • Journal Title: Annu Int Conf IEEE Eng Med Biol Soc. 2021 Volume: - Pages: 3713-3716
  • DOI: 10.1109/embc46164.2021.9630956
  • Peer Reviewed
• [Journal Article] Visualization and quantitative analyses for mouse embryonic stem cell tracking by manipulating hierarchical data structures using time-lapse confocal microscopy images (2021)
  • Author(s): Yokota Hideo、Abe Kuniya、Chang Yuan-Hsiang、Cho Dooseon、Tsai Ming- Dar、Huang Pin-Han
  • Journal Title: Annu Int Conf IEEE Eng Med Biol Soc. 2021 Volume: - Pages: 2944-2947
  • DOI: 10.1109/embc46164.2021.9629490
  • Peer Reviewed
• [Journal Article] Automatic three-dimensional segmentation of mouse embryonic stem cell nuclei by utilising multiple channels of confocal fluorescence images (2021)
  • Author(s): Chang YH , Yokota H, Abe K, Tsai MD, Chu SL
  • Journal Title: J Microsc Volume: 281 Issue: 1 Pages: 57-75
  • DOI: 10.1111/jmi.12949
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Epigenetic effects of insecticides on early differentiation of mouse embryonic stem cells. (2021)
  • Author(s): Wang W, Ito T, Otsuka S, Nansai H, Abe K, Nakao Y, Ohgane J, Yoneda M, Sone H.
  • Journal Title: Toxicol In Vitro Volume: 15 Pages: 105174-105174
  • DOI: 10.1016/j.tiv.2021.105174
  • Peer Reviewed / Open Access
• [Journal Article] House mouse Mus musculus dispersal in East Eurasia inferred from 98 newly determined complete mitochondrial genome sequences. (2021)
  • Author(s): Li Y, Fujiwara K, Osada N, Kawai Y, Takada T, Kryukov AP, Abe K, Yonekawa H, Shiroishi T, Moriwaki K, Saitou N, Suzuki H
  • Journal Title: Heredity Volume: 126 Issue: 1 Pages: 132-147
  • DOI: 10.1038/s41437-020-00364-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human induced pluripotent stem cell region detection in bright-field microscopy images using convolutional neural networks (2019)
  • Author(s): Chang Y-H, Abe K, Yokota H, Sudo K, Nakamura Y, Tsai M-D
  • Journal Title: Biomedical Engineering: applications, basis and communications Volume: 31 Issue: 02 Pages: 1950009-1950009
  • DOI: 10.4015/s1016237219500091
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] WNT inhibition and increased FGF signaling promotes derivation of less heterogeneous primed human embryonic stem cells, compatible with differentiation (2019)
  • Author(s): Taelman J, Popovic M, Bialecka M, Tilleman L, Warrier S, Van Der Jeught M, Menten B, Deforce D, Sutter P DE, Nieuwerburgh V, Abe K, Heindryckx B, Chuva de Sausa Lopes SM
  • Journal Title: Stem Cells and Development Volume: in press Issue: 9 Pages: 579-592
  • DOI: 10.1089/scd.2018.0199
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Xist/Tsix expression dynamics during mouse peri-implantation development revealed by whole-mount 3D RNA-FISH (2019)
  • Author(s): Shiura H, Abe K.
  • Journal Title: Sci Rep. Volume: 9 Issue: 1 Pages: 3637-3637
  • DOI: 10.1038/s41598-019-38807-0
  • Peer Reviewed / Open Access
• [Journal Article] Cell Type-Specific Survey of Epigenetic Modifications by Tandem Chromatin Immunoprecipitation Sequencing (2018)
  • Author(s): Mito Mari、Kadota Mitsutaka、Tanaka Kaori、Furuta Yasuhide、Abe Kuniya、Iwasaki Shintaro、Nakagawa Shinichi
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 1143-1143
  • DOI: 10.1038/s41598-018-19494-9
  • NAID: 120006398777
  • Peer Reviewed / Open Access
• [Journal Article] A simplified and efficient protocol for derivation and maintenance of high-quality mouse primed pluripotent stem cells using Wnt inhibition (2018)
  • Author(s): Kondo M, Sugimoto M, Abe K.
  • Journal Title: Curr Protoc Stem Cell Biol. Volume: 46 Issue: 1
  • DOI: 10.1002/cpsc.60
  • Peer Reviewed / Open Access
• [Journal Article] Female mice lacking Ftx lncRNA exhibit impaired X-chromosome inactivation and a microphthalmia-like phenotype. (2018)
  • Author(s): Hosoi Y, Soma M, Shiura H, Sado T, Hasuwa H, Abe K, Kohda T, Ishino F, Kobayashi S
  • Journal Title: Nat Commun Volume: 9(1） Issue: 1 Pages: 4618-4618
  • DOI: 10.1038/s41467-018-06327-6
  • Peer Reviewed / Open Access
• [Journal Article] RNA-FISH and Immunofluorescence of Mouse Preimplantation and Postimplantation Embryos (2018)
  • Author(s): Shiura H, Sakata, Abe K, Sado T.
  • Journal Title: Methods Mol Biol. Volume: 1861 Pages: 161-176
  • DOI: 10.1007/978-1-4939-8766-5_13
  • ISBN: 9781493987658, 9781493987665
  • Peer Reviewed
• [Journal Article] SCPortalen: human and mouse single-cell centric database (2017)
  • Author(s): Abugessaisa Imad、Noguchi Shuhei、Bottcher Michael、Hasegawa Akira、Kouno Tsukasa、Kato Sachi、Tada Yuhki、Ura Hiroki、Abe Kuniya、Shin Jay W、Plessy Charles、Carninci Piero、Kasukawa Takeya
  • Journal Title: Nucleic Acids Research Volume: 46 Issue: D1 Pages: D781-D787
  • DOI: 10.1093/nar/gkx949
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Locus coeruleus input to hippocampal CA3 drives single-trial learning of a novel context (2017)
  • Author(s): Wagatsuma Akiko、Okuyama Teruhiro、Sun Chen、Smith Lillian M.、Abe Kuniya、Tonegawa Susumu
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 115 Issue: 2 Pages: 2-2
  • DOI: 10.1073/pnas.1714082115
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Single cell transcriptome analyses reveal novel intermediate pluripotent states during transition from naive to primed pluripotent stem cells (2019)
  • Author(s): Tada Y, Bottcher M, Kondo M, Ura H, Carninci P, Carninci P, Abe K
  • Organizer: EMBO Workshop Single Cell Biology
  • Int'l Joint Research
• [Presentation] マウス初期発生過程におけるGARP complexの役割 (2019)
  • Author(s): 杉本道彦、阿部訓也
  • Organizer: 2019年度モロシヌス研究会
• [Presentation] 着床前後のマウス胚におけるトランスクリプトーム動態解析とDNAメチル化の役割 Transcriptome dynamics and DNA methylation in mouse peri-implantation embryos (2019)
  • Author(s): 田夛祐喜、志浦寛相、阿部訓也
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] Molecular characterizations of developing male germ cells and GS cell lines by single cell transcriptome analysis (2019)
  • Author(s): Kuniya Abe
  • Organizer: The 4th URICAS Symposium
  • Int'l Joint Research
• [Presentation] Ectopic expression of Ctcfl/Boris in multipotent mouse embryoid body affects the embryonic differentiation program in vitro (2019)
  • Author(s): Maisarah Ab Samad, Shinnosuke Suzuki, Kuniya Abe, Daruliza Kernain Mohd Azman, Shaharum Shamsuddin
  • Organizer: International Congress on ageing
  • Int'l Joint Research
• [Presentation] シングルセルRNA-Seq解析によるナイーブ型からプライム型への多能性幹細胞の変換過程における転写動態の解明 (2018)
  • Author(s): 田夛祐喜、浦大樹、Michael Boettcher、鈴木伸之介、Piero Carninci、阿部訓也
  • Organizer: 日本遺伝学会第90回大会
• [Presentation] シングルセルRNA-Seqを用いたオスES細胞プライム化過程における遺伝子発現動態解析 (2018)
  • Author(s): 田夛祐喜、阿部訓也
  • Organizer: 第41回日本分子生物学会年会
• [Patent(Industrial Property Rights)] 細胞の標識方法 (2022)
  • Inventor(s): 杉本道彦、阿部訓也
  • Industrial Property Rights Holder: 理化学研究所
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2022-016576
  • Filing Date: 2022