谱系追踪揭示肿瘤进化的系统动力学、可塑性和路径,Cell

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谱系追踪揭示肿瘤进化的系统动力学、可塑性和路径
Cell ( IF 45.5 ) Pub Date : 2022-05-05 , DOI: 10.1016/j.cell.2022.04.015
Dian Yang ₁ , Matthew G Jones ₂ , Santiago Naranjo ₃ , William M Rideout ₄ , Kyung Hoi Joseph Min ₅ , Raymond Ho ₁ , Wei Wu ₆ , Joseph M Replogle ₇ , Jennifer L Page ₈ , Jeffrey J Quinn ₉ , Felix Horns ₁₀ , Xiaojie Qiu ₁ , Michael Z Chen ₁₁ , William A Freed-Pastor ₁₂ , Christopher S McGinnis ₁₃ , David M Patterson ₁₄ , Zev J Gartner ₁₅ , Eric D Chow ₁₆ , Trever G Bivona ₆ , Michelle M Chan ₁₇ , Nir Yosef ₁₈ , Tyler Jacks ₃ , Jonathan S Weissman ₁₉

Affiliation

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Biological and Medical Informatics Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA; Integrative Program in Quantitative Biology, University of California, San Francisco, San Francisco, CA 94158, USA; Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Medical Scientist Training Program, University of California, San Francisco, San Francisco, CA 94158, USA; Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
Cell and Genome Engineering Core, University of California San Francisco, San Francisco, CA 94158, USA.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Medical Scientist Training Program, Harvard Medical School, Boston, MA 02115, USA.
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA; Chan Zuckerberg BioHub Investigator, University of California, San Francisco, San Francisco, CA 94158, USA; Center for Cellular Construction, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Center for Advanced Technology, University of California, San Francisco, San Francisco, CA 94158, USA.
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Chan Zuckerberg BioHub Investigator, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Electrical Engineering and Computer Science, University of California Berkeley, Berkeley, CA 94720, USA; Ragon Institute of Massachusetts General Hospital, MIT and Harvard University, Cambridge, MA, USA.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

肿瘤进化是由遗传和表观遗传改变的逐渐获得所驱动的，这些改变使得肿瘤能够不受控制地生长和扩展到邻近和远端组织。对癌细胞之间系统发育关系的研究为这些过程提供了重要的见解。在这里，我们将一种不断发展的谱系追踪系统与单细胞 RNA-seq 读数引入Kras;Trp53小鼠模型中（KP）驱动的肺腺癌，并以前所未有的分辨率追踪从单一转化细胞到转移性肿瘤的肿瘤演变。我们发现，初始稳定的类肺泡状态的丧失伴随着可塑性的短暂增加。随后采用了独特的转录程序，这些程序能够实现快速扩增，并最终对能够转移的稳定亚克隆进行克隆扫描。最后，肿瘤按照刻板的进化轨迹发展，扰乱额外的肿瘤抑制因子可以通过创造新的轨迹来加速进展。我们的研究阐明了肿瘤进化的层次性质，更广泛地说，使得能够深入研究肿瘤进展。

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更新日期：2022-05-05

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