郭國驥

2005年，畢業於武漢大學生命科學學院生物技術專業，獲學士學位。

2010年，畢業於新加坡國立大學及新加坡基因研究所，獲理學博士學位，並赴美國哈佛大學醫學院，任丹娜法伯癌症研究院及波士頓兒童醫院Research Fellow。

2014年，受聘於浙江大學醫學院幹細胞與再生醫學中心，擔任教授、博士生導師。 ^[5-6] 

2017年，獲“國家優秀青年基金”。 ^[1] 

2018年，獲“中國細胞生物學學會幹細胞生物學分會幹細胞青年研究員獎” ^[7] 

2019年，入選“萬人計劃”科技創新領軍人才 ^[8]  ，獲“樹蘭醫學青年獎” ^[2]  “中國細胞生物學會青年科學家獎” ^[3]  。

2020年，獲“霍英東青年教師獎” ^[4]  。

幹細胞與再生醫學

高通量單細胞分析技術

細胞圖譜

一、建立了高通量單細胞分析技術的若干實驗方法以及數據分析手段；

二、繪製世界首個小鼠細胞圖譜和首個人類細胞圖譜，並建立基於圖譜的單細胞比對系統；

三、利用單細胞分析技術系統性的解析了小鼠造血幹細胞的再生與分化機制；

四、利用單細胞分析技術解析了小分子組合誘導重編程的機制，併為再生醫學的細胞來源問題提供了新的思路。 ^[9] 

郭國驥團隊自主研發了低成本、高效率、完全國產化的高通量單細胞分析平台 ^[10]  ，並利用這一平台構建了全球首個小鼠細胞圖譜 ^[10-11]  和首個人類細胞圖譜 ^[12-13]  。

2022年9月20日，國家神經疾病醫學中心、復旦大學附屬華山醫院神經外科趙曜教授團隊和浙江大學郭國驥教授團隊合作在Cell Discovery（細胞發現）雜誌（影響因子38.1）在線發表有關“單細胞轉錄組測序發現脊索瘤內異質性，並指導後續開展靶向pEMT的臨牀試驗”的研究論文。研究團隊利用單細胞RNA測序技術首次在顱底脊索瘤惡性細胞中發現了一簇幹細胞樣細胞簇，且該細胞簇與腫瘤的放療抵抗密切相關。同時，該研究還揭示腫瘤細胞內存在p-EMT（partial epithelial-mesenchymal transition，不完全上皮-間質轉化）過程，與脊索瘤的侵襲性密切相關，可作為預後標誌物和治療新靶點。在此基礎上，趙曜教授團隊在華山醫院開展了I期臨牀試驗，並在3個脊索瘤病人中證實了服用p-EMT抑制劑（YL-13027）可以顯著減緩腫瘤生長，保持至少6個月的無進展狀態。該研究首次在單細胞層面發現了顱底脊索瘤中存在的幹細胞亞羣及p-EMT過程，並在實驗室中驗證了放療增敏劑及p-EMT抑制劑的治療效果，後續的臨牀試驗則進一步證實了p-EMT抑制劑的臨牀效果。 ^[25] 

Li J, Wang J, Zhang P, Wang R, Mei Y, Sun Z, Fei L, Jiang M, Ma L, E W, Chen H, Wang X, Fu Y, Wu H, Liu D, Wang X, Li J, Guo Q, Liao Y, Yu C, Jia D, Wu J, He S, Liu H, Ma J, Lei K, Chen J, Han X, Guo G. Deep learning of cross-species single-cell landscapes identifies conserved regulatory programs underlying cell types. Nat Genet. 2022 Nov;54(11):1711-1720. ^[31] 

Zhang Q, Fei L, Han R, Huang R, Wang Y, Chen H, Yao B, Qiao N, Wang Z, Ma Z, Ye Z, Zhang Y, Wang W, Wang Y, Kong L, Shou X, Cao X, Zhou X, Shen M, Cheng H, Yao Z, Zhang C, Guo G, Zhao Y. Single-cell transcriptome reveals cellular hierarchies and guides p-EMT-targeted trial in skull base chordoma. Cell Discov. 2022 Sep 20;8(1):94. ^[26] 

Fei L, Chen H, Ma L, E W, Wang R, Fang X, Zhou Z, Sun H, Wang J, Jiang M, Wang X, Yu C, Mei Y, Jia D, Zhang T, Han X, Guo G. Systematic identification of cell-fate regulatory programs using a single-cell atlas of mouse development. Nat Genet. 2022 Jul;54(7):1051-1061. ^[27] 

Chen H, Liao Y, Zhang G, Sun Z, Yang L, Fang X, Sun H, Ma L, Fu Y, Li J, Guo Q, Han X, Guo G. High-throughput Microwell-seq 2.0 profiles massively multiplexed chemical perturbation. Cell Discov. 2021 Nov 9;7(1):107. ^[28] 

Han X, Zhou Z, Fei L, Sun H, Wang R, Chen Y, Chen H, Wang J, Tang H, Ge W, Zhou Y, Ye F, Jiang M, Wu J, Xiao Y, Jia X, Zhang T, Ma X, Zhang Q, Bai X, Lai S, Yu C, Zhu L, Lin R, Gao Y, Wang M, Wu Y, Zhang J, Zhan R, Zhu S, Hu H, Wang C, Chen M, Huang H, Liang T, Chen J, Wang W, Zhang D, Guo G. Construction of a human cell landscape at single-cell level. Nature. Epub 2020 Mar 25. ^[12-13] 

Ma S, Sun S, Geng L, Song M, Wang W, Ye Y, Ji Q, Zou Z, Wang S, He X, Li W, Esteban CR, Long X, Guo G, Chan P, Zhou Q, Belmonte JCI, Zhang W, Qu J, Liu GH. Caloric Restriction Reprograms the Single-Cell Transcriptional Landscape of Rattus Norvegicus Aging. Cell. 2020 Mar 5;180(5):984-1001.e22. ^[14] 

Christodoulou C, Spencer JA, Yeh SA, Turcotte R, Kokkaliaris KD, Panero R, Ramos A, Guo G, Seyedhassantehrani N, Esipova TV, Vinogradov SA, Rudzinskas S, Zhang Y, Perkins AS, Orkin SH, Calogero RA, Schroeder T, Lin CP, Camargo FD. Live-animal imaging of native haematopoietic stem and progenitor cells. Nature. 2020 Feb;578(7794):278-283. ^[15] 

Chen H, Ye F, Guo G. Revolutionizing immunology with single-cell RNA sequencing. Cell Mol Immunol. 2019 Mar;16(3):242-249.

Jiang M, Chen H, Lai S, Wang R, Qiu Y, Ye F, Fei L, Sun H, Xu Y, Jiang X, Zhou Z, Zhang T, Li Y, Xie J, Fang Q, Gale RP, Han X, Huang H, Guo G. Maintenance of human haematopoietic stem and progenitor cells in vitro using a chemical cocktail. Cell Discov. 2018 Oct 30;4:59. ^[29] 

Lai S, Huang W, Xu Y, Jiang M, Chen H, Cheng C, Lu Y, Huang H, Guo G, Han X. Comparative transcriptomic analysis of hematopoietic system between human and mouse by Microwell-seq. Cell Discov. 2018 Jul 3;4:34. ^[30] 

Han X, Chen H, Huang D, Chen H, Fei L, Cheng C, Huang H, Yuan GC, Guo G. Mapping human pluripotent stem cell differentiation pathways using high throughput single-cell RNA-sequencing. Genome Biol. 2018 Apr 5;19(1):47. ^[16] 

Han X, Wang R, Zhou Y, Fei L, Sun H, Lai S, Saadatpour A, Zhou Z, Chen H, Ye F, Huang D, Xu Y, Huang W, Jiang M, Jiang X, Mao J, Chen Y, Lu C, Xie J, Fang Q, Wang Y, Yue R, Li T, Huang H, Orkin SH, Yuan GC, Chen M, Guo G. Mapping the Mouse Cell Atlas by Microwell-Seq.Cell. 2018 Feb 22; 172(5):1091-1107.e17. ^{[11]  [17]} 

Han X, Yu H, Huang D, Xu Y, Saadatpour A, Li X, Wang L, Yu J, Pinello L, Lai S, Jiang M, Tian X, Zhang F, Cen Y, Fujiwara Y, Zhu W, Zhou B, Zhou T, Ouyang H, Wang J, Yuan GC, Duan S, Orkin SH, Guo G. A molecular roadmap for induced multi-lineage trans-differentiation of fibroblasts by chemical combinations. Cell Res. 2017 Mar;27(3):386-401. ^[18] 

Ye F, Huang W, Guo G*. Studying hematopoiesis using single-cell technologies. Journal of Hematology & Oncology. 2017 Jan 21;10(1):27. ^[19] 

Beyaz S, Mana MD, Roper J, Kedrin D, Saadatpour A, Hong SJ, Bauer-Rowe KE, Xifaras ME, Akkad A, Arias E, Pinello L, Katz Y, Shinagare S, Abu-Remaileh M, Mihaylova MM, Lamming DW, Dogum R, Guo G, Bell GW, Selig M, Nielsen GP, Gupta N, Ferrone CR, Deshpande V, Yuan GC, Orkin SH, Sabatini DM, Yilmaz ÖH. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature. 2016 Mar 3;531(7592):53-8. ^[20] 

Guo G#，Pinello L, Han X, Lai S, Shen L, Lin TW, Zou K, Yuan GC#, Orkin SH#. Serum-based culture conditions provoke gene expression variability in mouse embryonic stem cells as revealed by single cell analysis. Cell Rep. 2016 Jan 19;14(4):956-65. #Co-corresponding authors. ^[20] 

Saadatpour A, Lai S, Guo G#, Yuan GC#. Single-Cell Analysis in Cancer Genomics. Trends Genet. 2015 Oct;31(10):576-86. doi: 10.1016/j.tig.2015.07.003. #Co-corresponding authors.

Saadatpour A*, Guo G*, Orkin SH, Yuan GC. Characterizing heterogeneity in leukemic cells using single-cell gene expression analysis. Genome Biol. Genome Biol. 2014 Dec 3;15(12):525. doi: 10.1186/s13059-014-0525-9. *Co-first authors.

Graham SL, Wicher KB, Jedrusik A, Guo G, Herath W, Robson P and Zernicka-Goetz M. BMP signalling regulates the pre-implantation development of extra-embryonic cell lineages in the mouse embryo. Nat Commun. 2014 Dec 16;5:5667. doi: 10.1038/ncomms6667.

Marco E, Karp RL, Guo G, Robson P, Hart AH, Trippa L, Yuan GC. Bifurcation analysis of single-cell gene expression data reveals epigenetic landscape. Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):E5643-50. doi: 10.1073/pnas.1408993111. Epub 2014 Dec 15.

Lundberg P, Takizawa H, Kubovcakova L, Guo G, Hao-Shen H, Dirnhofer S, Orkin SH, Manz MG, Skoda RC. Myeloproliferative neoplasms can be initiated from a single hematopoietic stem cell expressing JAK2-V617F. J Exp Med. 2014 Oct 20;211(11):2213-30. doi: 10.1084/jem.20131371. Epub 2014 Oct 6.

Riddell J, Gazit R, Garrison BS, Guo G, Saadatpour A, Mandal PK, Ebina W, Volchkov P, Yuan GC, Orkin SH, Rossi DJ. Reprogramming committed murine blood cells to induced hematopoietic stem cells with defined factors. Cell. 2014 Apr 24;157(3):549-64. doi: 10.1016/j.cell.2014.04.006.

Das PP, Shao Z, Beyaz S, Apostolou E, Pinello L, De Los Angeles A, O'Brien K, Atsma JM, Fujiwara Y, Nguyen M, Ljuboja D, Guo G, Woo A, Yuan GC, Onder T, Daley G, Hochedlinger K, Kim J, Orkin SH. Distinct and combinatorial functions of Jmjd2b/Kdm4b and Jmjd2c/Kdm4c in mouse embryonic stem cell identity. Mol Cell. 2014 Jan 9;53(1):32-48. doi: 10.1016/j.molcel.2013.11.011. Epub 2013 Dec 19.

Guo G, Luc S, Marco E, Lin TW, Peng C, Kerenyi MA, Beyaz S, Kim W, Xu J, Das PP, Neff T, Zou K, Yuan GC, Orkin SH. Mapping cellular hierarchy by single-cell analysis of the cell surface repertoire. Cell Stem Cell. 2013 Oct 3;13(4):492-505. doi: 10.1016/j.stem.2013.07.017. Epub 2013 Sep 12.

Kim W, Bird GH, Neff T, Guo G, Kerenyi MA, Walensky LD, Orkin SH. Targeted disruption of the EZH2-EED complex inhibits EZH2-dependent cancer. Nat Chem Biol. 2013 Oct;9(10):643-50. doi: 10.1038/nchembio.1331. Epub 2013 Aug 25.

Kerenyi MA, Shao Z, Hsu YJ, Guo G, Luc S, O'Brien K, Fujiwara Y, Peng C, Nguyen M, Orkin SH. Histone demethylase Lsd1 represses hematopoietic stem and progenitor cell signatures during blood cell maturation. Elife. 2013 Jun 18;2:e00633. doi: 10.7554/eLife.00633.

Do DV, Ueda J, Messerschmidt DM, Lorthongpanich C, Zhou Y, Feng B, Guo G, Lin PJ, Hossain MZ, Zhang W, Moh A, Wu Q, Robson P, Ng HH, Poellinger L, Knowles BB, Solter D, Fu XY. A genetic and developmental pathway from STAT3 to the OCT4-NANOG circuit is essential for maintenance of ICM lineages in vivo. Genes Dev. 2013 Jun 15;27(12):1378-90. doi: 10.1101/gad.221176.113.

Maclean GA, Menne TF, Guo G, Sanchez DJ, Park IH, Daley GQ, Orkin SH. Altered hematopoiesis in trisomy 21 as revealed through in vitro differentiation of isogenic human pluripotent cells. Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17567-72. doi: 10.1073/pnas.1215468109. Epub 2012 Oct 8.

Guo G, Huss M, Tong GQ, Wang C, Li Sun L, Clarke ND, Robson P. Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst. Dev Cell. 2010 Apr 20;18(4):675-85. doi:10.1016/j.devcel.2010.02.012.

Ralston A, Cox BJ, Nishioka N, Sasaki H, Chea E, Rugg-Gunn P, Guo G, Robson P, Draper JS, Rossant J. Gata3 regulates trophoblast development downstream of Tead4 and in parallel to Cdx2. Development. 2010 Feb;137(3):395-403. doi:10.1242/dev.038828.

Yuan P, Han J, Guo G, Orlov YL, Huss M, Loh YH, Yaw LP, Robson P, Lim B, Ng HH. Eset partners with Oct4 to restrict extraembryonic trophoblast lineage potential in embryonic stem cells. Genes Dev. 2009 Nov 1;23(21):2507-20. doi: 10.1101/gad.1831909.

Jedrusik A, Parfitt DE, Guo G, Skamagki M, Grabarek JB, Johnson MH, Robson P, Zernicka-Goetz M. Role of Cdx2 and cell polarity in cell allocation and specification of trophectoderm and inner cell mass in the mouse embryo. Genes Dev. 2008 Oct 1;22(19):2692-706. doi: 10.1101/gad.486108. ^[21] 

浙江大學醫學院郭國驥教授團隊用自主研發的分析平台，繪製出人類首個細胞圖譜。3月26日，國際頂級期刊《自然》在線刊登了這項研究成果。

研究團隊對60種人體組織樣品和7種細胞培養樣品進行了高通量單細胞測序分析，系統性地繪製了跨越胚胎和成年兩個時期、涵蓋八大系統的人類細胞圖譜，建立了70多萬個單細胞的轉錄組數據庫，鑑定了人體100餘種細胞大類和800餘種細胞亞類，開發了單細胞比對系統，並搭建了人類細胞藍圖網站。郭國驥介紹，這項工作概括地説就是人體細胞數字化。

該研究首次從單細胞水平上全面分析了胚胎和成年時期的人體細胞種類，研究數據將成為探索細胞命運決定機制的資源寶庫，也將對人體正常與疾病細胞狀態的鑑定帶來深遠影響。在未來，臨牀醫生有望通過參照正常的細胞來鑑別異常的細胞狀態和起源。 ^[22] 

2022年2月15日，表彰郭國驥為青年科技英才。 ^[23] 

2022年9月，榮獲第十四屆“談家楨生命科學獎”（談家楨生命科學創新獎）。 ^[24]