郭國驥

2010.8-2010.10新加坡基因研究所 博士后

2010.11-2014.9美國哈佛大學醫學院 Research Fellow

2014.10-浙江大學醫學院教授、博士生導師

2020年，獲“霍英東教育基金會第十七屆高等院校青年教師獎”。

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，並為再生醫學的細胞來源問題提供了新的思路。

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，並利用這一平台構建了全球首個小鼠細胞圖譜和首個人類細胞圖譜

利用單細胞基因表達譜分析的手段來研。究幹細胞的分化路徑和分化機制，開闢了單細胞系統生物學新領域。建立並優化了高通量單細胞定量PCR的基本實驗方法，以及數據分析手段。構建Microwell-seq高通量單細胞分析平台，並繪製全球首個哺乳動物細胞圖譜。在胚胎期幹細胞系統和成體造血幹細胞系統中發現了譜系基因預表達的現象，解析了這一現象的分子機制，並進一步闡明了其對幹細胞終端分化的影響。五年內在Cell, Cell Stem Cell, Developmental Cell等著名期刊發表學術論文10餘篇，總影響因子180分，總引用率650餘次。

2020年3月26日，世界首個人類細胞圖譜日前在浙江大學繪製成功。國際頂級期刊《自然》在線刊登了浙江大學醫學院郭國驥教授團隊的這項最新研究成果。

發表文章

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.

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.

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.

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.

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.

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.

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資料庫，鑒定了人體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，這項工作概括地說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鑒定帶來深遠影響。在未來，臨床醫生有望通過參照正常的細胞來鑒別異常的細胞狀態和起源。