生命是如何產(chǎn)生的？如何變復(fù)雜的？意識(shí)的本質(zhì)是什么？這是生物學(xué)的三大關(guān)鍵問題，我們?cè)噲D通過細(xì)胞命運(yùn)和表觀遺傳的研究，對(duì)第二個(gè)問題做出關(guān)鍵推進(jìn)，并引導(dǎo)到第三個(gè)問題。

細(xì)胞是生命活動(dòng)的基本單位，從進(jìn)化角度看，細(xì)胞先經(jīng)歷了細(xì)胞內(nèi)結(jié)構(gòu)的特化和功能的擴(kuò)展，之后才開始多細(xì)胞生物的進(jìn)化，多細(xì)胞生物個(gè)體則包含多種具備獨(dú)特功能的細(xì)胞。多細(xì)胞生物的個(gè)體發(fā)育是幾乎不涉及基因序列改變的，那這些細(xì)胞如何被引導(dǎo)到特定的細(xì)胞狀態(tài)呢？這個(gè)問題被稱為細(xì)胞命運(yùn)決定，涉及表觀遺傳學(xué)、信號(hào)轉(zhuǎn)導(dǎo)等等一系列基本科學(xué)問題。生命活動(dòng)之所以難以理解，在于影響一個(gè)現(xiàn)象（如細(xì)胞命運(yùn)）的因素是多維度的，這也是目前在細(xì)胞再生治療等實(shí)踐中所遇到的理論困難的根本原因。因此進(jìn)一步了解細(xì)胞命運(yùn)決定各因素之間的相互聯(lián)系，將能夠?qū)M(jìn)化中多細(xì)胞生物其細(xì)胞組織功能的形成有更深入的了解，也將有機(jī)會(huì)創(chuàng)造了解這種多維度支配下的生物系統(tǒng)的嶄新思維模式。

細(xì)胞命運(yùn)決定一方面是干細(xì)胞應(yīng)用技術(shù)所亟需的基本理論，另一方面更是從細(xì)胞生物學(xué)角度理解多細(xì)胞生物生命活動(dòng)的重要基礎(chǔ)研究命題。我們?cè)谶^去的研究中揭示表觀遺傳因素如組蛋白甲基化是如何被細(xì)胞外環(huán)境、核心轉(zhuǎn)錄因子所影響、進(jìn)而決定細(xì)胞命運(yùn)的，發(fā)展了一系列追蹤復(fù)雜細(xì)胞命運(yùn)中轉(zhuǎn)錄信息和非編碼序列信息變化的新算法。我們的長遠(yuǎn)目標(biāo)是通過這一系列研究，清晰地理解多細(xì)胞生物的功能組織過程，提出新的生物學(xué)研究思路及理論，也希望將這種知識(shí)運(yùn)用到人類健康事業(yè)上。

主要研究方向

1）以干細(xì)胞模型（如類器官、重編程等）研究細(xì)胞命運(yùn)決定的分子調(diào)控機(jī)理；主要探討表觀遺傳調(diào)控的特異性機(jī)制，及其與信號(hào)轉(zhuǎn)導(dǎo)、轉(zhuǎn)錄因子、非編碼遺傳信息之間的聯(lián)系。

2）以細(xì)胞命運(yùn)轉(zhuǎn)化模型中采集的表觀遺傳組和單細(xì)胞轉(zhuǎn)錄組等大數(shù)據(jù)，通過計(jì)算生物學(xué)挖掘重要生物學(xué)機(jī)理，根據(jù)新理論開發(fā)新算法和新軟件。

3）通過細(xì)胞命運(yùn)決定理論促進(jìn)干細(xì)胞誘導(dǎo)分化的技術(shù)實(shí)踐（旨在獲得具有體內(nèi)功能的細(xì)胞，目前這仍是主要瓶頸），從而推進(jìn)再生醫(yī)學(xué)發(fā)展。

核心技術(shù)平臺(tái)

1.干細(xì)胞培養(yǎng)與分化，包括類器官3D培養(yǎng)和化學(xué)生物學(xué)方法；

2.先進(jìn)的干細(xì)胞遺傳學(xué)和小鼠遺傳學(xué)系統(tǒng)，應(yīng)用遺傳學(xué)手段實(shí)現(xiàn)可信的科學(xué)證明；

3.前沿的生物學(xué)信息學(xué)研究能力，基于理論創(chuàng)新需求的算法開發(fā)能力。

國家自然科學(xué)獎(jiǎng)二等獎(jiǎng) （2018）

廣東省青年科技創(chuàng)新獎(jiǎng)（2023）

第二十五屆廣東青年五四獎(jiǎng)?wù)拢?023）

第一屆中國科學(xué)院青年五四獎(jiǎng)?wù)拢?022）

廣東省科學(xué)技術(shù)一等獎(jiǎng)（2015）；

廣州市科學(xué)技術(shù)一等獎(jiǎng)（2015）；

中國科學(xué)院杰出成就獎(jiǎng)（團(tuán)隊(duì)，2017）；

中國科學(xué)院卓越青年科學(xué)家（2014）；

廣東省南粵創(chuàng)新獎(jiǎng)（團(tuán)隊(duì)，2017）；

連續(xù)三年（2020-2022）獲得中國科學(xué)院優(yōu)秀導(dǎo)師榮譽(yù)稱號(hào)等。

（*為通訊作者），以下工作更新于2024年，完整論文信息請(qǐng)見https://pubmed.ncbi.nlm.nih.gov/?term=jiekai+chen

2024年

1.??????? Shan, Ziyun, Yingying Zhao, Xiuyu Chen, Guodong Zhan, Junju Huang, Xuejie Yang, Chongshen Xu, ; …;?Jiekai Chen*;? KMT2D Deficiency Leads to Cellular Developmental Disorders and Enhancer Dysregulation in Neural-Crest-Containing Brain Organoids, Science Bulletin ,2024,69(22): 3533–46.（闡明KMT2D缺失影響神經(jīng)元及神經(jīng)嵴分化異常的分子機(jī)制）

2.??????? Lai, Wanjing, Yingying Zhao, Yalan Chen, Zhenzhu Dai, Ruhai Chen, Yimei Niu, Xiaoxia Chen; …;?Jiekai Chen*;? Autism Patient-Derived SHANK2BY29X Mutation Affects the Development of ALDH1A1 Negative Dopamine Neuron, Molecular Psychiatry ,2024,29(10): 3180–94.（自閉癥患者的SHANK2BY29X突變影響ALDH1A1陰性多巴胺神經(jīng)元的發(fā)育）

2023年

3.??????? Cao, Shangtao, Huijian Feng, Hongyan Yi, Mengjie Pan, Lihui Lin, Yao Santo Zhang, Ziyu Feng; …;?Jiekai Chen*;? Single-Cell RNA Sequencing Reveals the Developmental Program Underlying Proximal–Distal Patterning of the Human Lung at the Embryonic Stage,?Cell Research ,2023,33(6): 421–33.（開發(fā)單細(xì)胞測(cè)序技術(shù)解析胎肺發(fā)育的近-遠(yuǎn)端特化進(jìn)程）

2021年

4.??????? Jiadong Liu^#; Mingwei Gao^#; Jiangping He^#; Kaixin Wu; Siyuan Lin; Lingmei Jin; …;?Jiekai Chen*;?The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity,?Nature, 2021, 591(7849): 322-326.?(發(fā)現(xiàn)RNA m6A調(diào)控異染色質(zhì)和干細(xì)胞的新功能)?

5.??????? Jiangping He; …; Andrew P. Hutchins*;?Jiekai Chen*;?Identifying transposable element expression dynamics and heterogeneity during development at the single-cell level with a processing pipeline scTE,?Nature Communications, 2021, 12(1): 1456.?(開發(fā)單細(xì)胞測(cè)序分析轉(zhuǎn)座元件的新工具)?

6.??????? Feng-Liang Liu^#; Kaixin Wu^#; Jiaoyang Sun^#; Zilei Duan^#; Xiongzhi Quan; …; Guangming Wu*; Yong-Tang Zheng*;?Jiekai Chen*;?Rapid generation of ACE2 humanized inbred mouse model for COVID-19 with tetraploid complementation,?National Science Review, 2021.?（新一代動(dòng)物模型技術(shù)，35天制備新冠易感小鼠）

7.??????? ?Xianwen Ren^#; Wen Wen^#; Xiaoying Fan^#; …; Hongyang Wang*; Bing Su*; Zheng Zhang*; Kun Qu*; Xiaoqun Wang*;?Jiekai Chen*; Ronghua Jin*; Zemin Zhang*;?COVID-19 immune features revealed by a large-scale single cell transcriptome atlas,?Cell, 2021.?(新冠肺炎單細(xì)胞研究中國聯(lián)盟，限于篇幅未列出所有重要作者)?

2020年

8.??????? Kaixin Wu^#; He Liu^#; Yaofeng Wang; Jiangping He; …;?Jiekai Chen*;?SETDB1-Mediated Cell Fate Transition between 2C- Like and Pluripotent States,?Cell Reports, 2020, 30(1): 25-36.?(發(fā)現(xiàn)H3K9甲基化酶SETDB1調(diào)控干細(xì)胞多能性和全能性)

9.??????? Jiadong Liu^#; Mingwei Gao^#; …;?Jiekai Chen*;?YTHDF2/3 Are Required for Somatic Reprogramming through Different RNA Deadenylation Pathways,?Cell Reports, 2020, 32(10): 108120.?

10.???? Jiekai Chen*;?Perspectives on somatic reprogramming: spotlighting epigenetic regulation and cellular heterogeneity,?Current Opinion in Genetics & Development, 2020, 64: 21-25.

11.???? ?Jiangping He^#; Shuijiang Cai^#; Huijian Feng^#; Baomei Cai^#; Lihui Lin^#; Yuanbang Mai; …; Nanshan Zhong; Xinwen Chen*; Xilong Deng*;?Jiekai Chen*;?Single-cell analysis reveals bronchoalveolar epithelial dysfunction in COVID-19 patients,?Protein & Cell, 2020, 11(9): 680-687.

12.???? Xiaowei Lai^#; Qian Li^#; Fang Wu; Jiechun Lin;?Jiekai Chen*; Hui Zheng*; Lin Guo*;?Epithelial-Mesenchymal Transition and Metabolic Switching in Cancer: Lessons From Somatic Cell Reprogramming,?Front Cell Dev Biol, 2020 , 8:760.

13.???? Linlin Hou*; Yuanjie Wei; …;?Jiekai Chen; Xichen Bao*; Ralf Jauch*;?Concurrent binding to DNA and RNA facilitates the pluripotency reprogramming activity of Sox2,?Nucleic Acids Research, 2020, 48(7): 3869-3887.

14.???? Jing Sun^#; Zhen Zhuang^#; Jian Zheng^#; …;?Jiekai Chen; Yimin Li; Nanshan Zhong; David K. Meyerholz; Paul B. McCray, Jr.*; Stanley Perlman*; Jincun Zhao*;?Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment,?Cell, 2020, 182(3): 734-+.

15.???? Shengyong Yu^#; Chunhua Zhou^#; Shangtao Cao^#; Jiangping He^#; …;?Jiekai Chen; Jing Liu*; Duanqing Pei*;?BMP4 resets mouse epiblast stem cells to naive pluripotency through ZBTB7A/B-mediated chromatin remodelling,?Nature Cell Biology, 2020, 22(6): 651-+.

2013-2019年

16.???? Lin Guo^#; Lihui Lin^#; Xiaoshan Wang^#; Mingwei Gao; Shangtao Cao; Yuanbang Mai; Fang Wu; …; Duanqing Pei*;?Jiekai Chen*;?Resolving Cell Fate Decisions during Somatic Cell Reprogramming by Single-Cell RNA-Seq,?Molecular Cell, 2019, 73(4): 815-829.?(建立SOT算法，對(duì)iPS重編程過程的細(xì)胞命運(yùn)決定過程進(jìn)行了新闡述)

17.???? Zhiwei Zhou; Xuejie Yang; Jiangping He; …; Andrew P. Hutchins; Duanqing Pei*;?Jiekai Chen*;?Kdm2b Regulates Somatic Reprogramming through Variant PRC1 Complex-Dependent Function,?Cell Reports, 2017, 21(8): 2160-2170.

18.???? Dongwei Li^#; Jing Liu^#; Xuejie Yang^#; …; Andrew P. Hutchins*;?Jiekai Chen*; Duanqing Pei*;?Chromatin Accessibility Dynamics during iPSC Reprogramming,?Cell Stem Cell, 2017, 21(6): 819-833.

19.???? Jing Liu; Qingkai Han; Tianran Peng; …; Guangjin Pan;?Jiekai Chen*; Duanqing Pei*;?The oncogene c-Jun impedes somatic cell reprogramming,?Nature Cell Biology, 2015, 17(7): 856-867.

20.???? Jiangping He; Xiuling Fu; Meng Zhang; …;?Jiekai Chen; Miguel A. Esteban; Andrew P. Hutchins*;?Transposable elements are regulated by contextspecific patterns of chromatin marks in mouse embryonic stem cells,?Nature Communications, 2019, 10(1): 34.

21.???? Alejandro De Los Angeles^#; Francesco Ferrari^#; …;?Jiekai Chen; Marti Borkent; Vladislav Krupalnik; Ernesto Lujan; Marius Wernig; Jacob H. Hanna; Konrad Hochedlinger; Duanqing Pei; Rudolf Jaenisch; Hongkui Deng; Stuart H. Orkin; Peter J. Park*; George Q. Daley*;?Failure to replicate the STAP cell phenomenon,?Nature, 2015, 525(7570): E6-9.

22.???? Mengyun Zhang^#; Yong Dong^#; Fangxiao Hu^#; …;?Jiekai Chen; Aibin He; Bing Liu; Demin Wang; Yong-Guang Yang; Jinyong Wang*;?Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes,?Nature Immunology, 2018, 19(3): 279-290.

23.???? Shangtao Cao^#; Shengyong Yu^#; Dongwei Li^#; Jing Ye; Xuejie Yang; …; Guangjin Pan;?Jiekai Chen; Jing Liu*; Duanqing Pei*;?Chromatin Accessibility Dynamics during Chemical Induction of Pluripotency,?Cell Stem Cell, 2018, 22(4): 529-542.

24.???? Jiekai Chen^#; He Liu^#; Jing Liu; Jing Qi; Bei Wei; Jiaqi Yang; Hanquan Liang; You Chen; et al.?H3K9 methylation is a barrier during somatic cell reprogramming into iPSCs,?Nature Genetics, 2013, 45(1): 34-42.?（首次闡明H3K9甲基化是重編程的重要障礙，ESI高引論文）

25.???? Jiekai Chen^#; Lin Guo^#; Lei Zhang^#; Haoyu Wu; Jiaqi Yang; He Liu; et al.?Vitamin C modulates TET1 function during somatic cell reprogramming,?Nature Genetics, 2013, 45(12): 1504-1509.?（闡明Vc對(duì)Tet1的功能的轉(zhuǎn)化作用，當(dāng)期雜志配發(fā)評(píng)論）