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专家人才

  • 姓名: 景乃禾
  • 性别: 男
  • 职称: 研究员
  • 学历: 博士
  • 电话: 
  • 传真: 
  • 电子邮件: 
  • 通讯地址 广州市黄埔区开源大道190号

    简历:

  • Educational Background:

    1978-1982           B.Sc. in Chemistry

    Nanjing University

    Nanjing, China

    1982-1988          Ph.D. in Biochemistry

    Shanghai Institute of Biochemistry

    Chinese Academy of Sciences

    Shanghai, China               

    Professional Background:

    2017-                   Professor, Principal Investigator

    Shanghai Institute of Biochemistry and Cell Biology

    Chinese Academy of Sciences

    2014-2017           Professor, Group Leader

    Institute of Biochemistry and Cell Biology

    Shanghai Institutes for Biological Sciences

    Chinese Academy of Sciences 

    2008-2014           Professor, Executive Director, Group Leader

    Institute of Biochemistry and Cell Biology

    Shanghai Institutes for Biological Sciences

    Chinese Academy of Sciences

    2005-2008           Professor, Deputy Director, Group Leader

    Institute of Biochemistry and Cell Biology

    Shanghai Institutes for Biological Sciences

    Chinese Academy of Sciences 

    2000-2004          Professor, Assistant Director, Group Leader

    Institute of Biochemistry and Cell Biology

    Shanghai Institutes for Biological Sciences

    Chinese Academy of Sciences 

    1995-2000           Professor, Group Leader

    Shanghai Institute of Biochemistry

    Chinese Academy of Sciences

    1991-1995           Associate Professor, Group Leader

    Shanghai Institute of Biochemistry

    Chinese Academy of Sciences

    2018.11-12          Visiting Professor

                                Tel Aviv University, Tel Aviv, Israel

    2018.05               Visiting Professor

                                Hong Kong University of Science and Technology

                                Hong Kong, China

    2015. 7-8             Visiting Professor

                                Stowers Institute for Medical Research

    Kansas City, Missouri, USA

    2013. 3-5             Visiting Professor

    Weizmann Institute of Science, Rehovot, Israe 

    2010. 7-8             Visiting Professor

    Ben May Department for Cancer Research

    University of Chicago, Chicago, USA

    2006. 7-8             Visiting Professor

    Division of Molecular Neurobiology

    National Institute for Medical Research

    Medical Research Counsel, London, UK

    2004. 6-8             Visiting Professor

                                Sunnybrook Research Institute

                                Sunnybrook Health Sciences Centre

    University of Toronto, Toronto, Canada 

    2002. 12              Visiting Professor

                                Graduate School of Frontier Biosciences

    Osaka University, Osaka, Japan 

    2000. 6-9             Visiting Professor

                                Division of Morphogenesis

                                Institute of Molecular Embryology and Genetics

                                Kumamoto University School of Medicine, Japan

    1996-1997           Visiting Scholar

                                Department of Molecular Cell Biology

                                Max Planck Institute of Biophysical Chemistry, Germany 

    1995. 8-11           Visiting Scholar

                                Insitut de Genetique et de Biologie Moleculaire et Cellulaire, France

    1992-1993           Visiting Scholar

                                The Institute of Physical and Chemical Research (RIKEN), Japan 

    1989-1991           Postdoctoral Research Fellow

                                The Institute of Physical and Chemical Research (RIKEN)

    Tsukuba, Japan

     

    研究领域:

    承担科研项目情况:

    社会任职:

    获奖及荣誉:

    代表论著:

  • 1.       Ting Zhang, Qingqing Zhu, Zhihui Xie, Yongfeng Chen, Yunbo Qiao, Lingyu Li, Naihe Jing*. The zinc-finger transcription factor Ovol2 acts downstream of the BMP pathway to regulate the cell fate decision between neuroectoderm and mesendoderm. J Biol Chem 2013, 288:6166-6177.

    2.       Lingyu Li, Chang Liu, Steffen Biechele, Qingqing Zhu, Lu Song, Fredrik Lanner, Naihe Jing and Janet Rossant*. Location of transient ectodermal progenitor potential in mouse development. Development 2013, 140:4533-4543.

    3.       Xingxing Xu, Yonghui Tao, Xing Fu,Tao Yu, Yuanyuan Li, Kan Chen, Xiaoyan Ding, Kangcheng Ruan, Naihe Jing*, Ronggui Hu*. ZIP-seq: genome-wide mapping of trinucleotide repeats at single-base resolution. Journal of Molecular Cell Biology 2014, 6:93-96.

    4.       Qingqing Zhu, Lu Song, Guangdun Peng, Na Sun, Jun Chen, Ting Zhang, Nengyin Sheng, Wei Tang, Cheng Qian, Yunbo Qiao, Ke Tang, Jing-Dong Jackie Han, Jinsong Li, Naihe Jing*. The transcription factor Pou3f1 promotes neural fate commitment via activation of neural lineage genes and inhibition of external signaling pathways. eLife 2014, 3:e02224. DOI: 10.7554/eLife.02224

    5.       Yunbo Qiao, Ran Wang, Xianfa Yang, Ke Tang and Naihe Jing*. Dual roles of histone H3 lysine 9 acetylation in human embryonic stem cell pluripotency and neural differentiation. J Biol Chem 2015, 290:2508-2520.

    6.       Fangzhi Tan, Cheng Qian, Ke Tang, Saber Mohamed Abd-Allah and Naihe Jing*. Inhibition of TGF-β signaling can substitute for Oct4 in reprogramming and maintain pluripotency. J Biol Chem 2015, 290:4500-4511.

    7.       Pingyu Liu, Xiaoyang Dou, Chang Liu, Lingbo Wang, Can Xing, Guangdun Peng, Jun Chen, Fang Yu,Yunbo Qiao, Lu Song, Yuxuan Wu, Chunmei Yue, Jinsong Li, Jing-Dong J. Han, Ke Tang & Naihe Jing*. Histone deacetylation promotes mouse neural induction by restricting Nodal-dependent mesendoderm fate. Nature Communications 2015, DOI: 10.1038/ncomms7830

    8.       Wanqu Zhu, Xiao Yao, Yan Liang, Dan Liang, Lu Song, Naihe Jing, Jinsong Li and Gang Wang*. Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling. Development 2015, 142:465-476.

    9.       Lingyu Li, Lu Song, Chang Liu, Jun Chen, Guangdun Peng, Ran Wang, Pingyu Liu, Ke Tang, Janet Rossant, Naihe Jing*. Ectodermal progenitors derived from epiblast stem cells by inhibition of Nodal signaling. Journal of Molecular Cell Biology 2015, 7:455-465.

    10.    Ke Tang*, Guangdun Peng, Yunbo Qiao, Lu Song, Naihe Jing*. The intrinsic regulations in neural fate commitment. Develop Growth Differ 2015, 57:109-120. (Review)

    11.    Yunbo Qiao, Xiongjun Wang, Ran Wang, Yuanyuan Li, Fang Yu, Xianfa Yang, Lu Song, Guoliang Xu, Y. Eugene Chin*, Naihe Jing*. AF9 Promotes hESC neural differentiation through recruiting TET2 to neurodevelopmental gene loci for methylcytosine hydroxylation. Cell Discovery 2015, 1:15017. DOI 10.1038/celldisc.2015.17.

    12.    Chunmei Yue, Naihe Jing*. The promise of stem cells in the therapy of Alzheimer’s disease. Translational Neurodegeneration 2015, 4:8-12. DOI 10.1186/s40035-015-0029-x (Review)

    13.    Pingyu Liu, Xiaoyang Dou, Guangdun Peng, Jing-Dong Jackie Han, Naihe Jing*. Genome-wide analysis of histone acetylation dynamics during mouse embryonic stem cell neural differentiation. Genomics Data 2015, 5:15-16.

    14.    Wei Yue, Yuanyuan Li, Ting Zhang, Man Jiang, Yun Qian, Min Zhang, Nengyin Sheng, Su Feng, Ke Tang, Xiang Yu, Yousheng Shu, Chunmei Yue*, Naihe Jing*. ESC-derived basal forebrain cholinergic neurons ameliorate the cognitive symptoms associated with Alzheimer’s disease in mouse models. Stem Cell Reports 2015, 5:776-790.

    15.    Lu Song, Na Sun, Guangdun Peng, Jun Chen, Jing-Dong Jackie Han, Naihe Jing*. Genome-wide ChIP-seq and RNA-seq analyses of Pou3f1 during mouse pluripotent stem cell neural fate commitment. Genomics Data 2015, 5:375-377.

    16.    Yunbo Qiao, Naihe Jing*. Human neural development and human embryonic stem cell neural differentiation. Stem Cells: Basics and Clinical Translation (R.C. Zhao ed.) 2015, pp189-199. DOI 10.1007/978-94-017-7273-0_8 (Review)

    17.    Junfeng Wang, Rui Lu, Jian Yang, Hongyu Li, Zhuohao He, Naihe Jing, Xiaomin Wang, Yizheng Wang*. TRPC6 specifically interacts with APP to inhibit its cleavage by g-secretase and reduce Ab production. Nature Communications 2015, DOI: 10.1038/ncomms9876

    18.    Yunbo Qiao, Xianfa Yang, Naihe Jing*. Epigenetic regulation of early neural fate commitment. Cell Mol Life Sci 2016, 73:1399-1411 (Review)

    19.    Guangdun Peng, Shengbao Suo, Jun Chen, Weiyang Chen, Chang Liu, Fang Yu, Ran Wang, Shirui Chen, Na Sun, Guizhong Cui, Lu Song, Patrick P.L. Tam, Jing-Dong Jackie Han*, Naihe Jing*. Spatial transcriptome for the molecular annotation of lineage fates and cell identity in mid-gastrula mouse embryo. Developmental Cell, 2016, 36:681–697.

    20.    Lu Song, Jun Chen, Guangdun Peng, Ke Tang, and Naihe Jing*. Dynamic heterogeneity of Brachyury in mouse epiblast stem cells mediates distinct response to extrinsic bone morphogenetic protein (BMP) signaling. J Biol Chem 2016, 290:15212-15225.

    21.    Chang Xie, Ya-Ping Zhang, Lu Song2, Jie Luo, Wei Qi, Jialu Hu, Danbo Lu, Zhen Yang, Jian Zhang,Jian Xiao, Bin Zhou, Jiu-Lin Du, Naihe Jing, Yong Liu, Yan Wang, Bo-Liang Li, Bao-Liang Song*, Yan Yan*. Genome editing with CRISPR/Cas9 in postnatal mice corrects PRKAG2 cardiac syndrome. Cell Res 2016, 26:1099–1111.

    22.    Jun Chen, Shengbao Suo, Patrick. P.L. Tam, Jing-Dong J. Han, Guangdun Peng*, Naihe Jing*. Spatial transcriptomic analysis of cryosectioned tissue samples with Geo-seq. Nature Protocols 2017, 12:566-580

    23.    Xiong-jun Wang, Yunbo Qiao, Minzhe M. Xiao, Lingbo Wang, Jun Chen, Wenjian Lv, Li Xu, Yan Li, Yumei Wang, Ming-dian Tan, Chao Huang, Jinsong Li, Ting C. Zhao, Zhaoyuan Hou*, Naihe Jing*, Y. Eugene Chin*. Opposing roles of acetylation and phosphorylation in LIFR-dependent self-renewal growth signaling in mouse embryonic stem cells. Cell Reports 2017, 18:933-946.

    24.    Lyad Zamir, Reena Singh, Elisha Nathan, Ralph Patrick, Oren Yifa, Yfat Yahalom-Ronen, Alaa Arraf, Thomas Schultheiss, Shengbao Suo, Jing-Dong Jackie Han, Guangdun Peng, Naihe Jing, Yuliang Wang, Nathan Palpant, Patrick Tam, Richard Harvey*, Eldad Tzahor*. Nkx2.5 marks angioblasts that contribute to hemogenic endothelium of the endocardium and dorsal aorta. eLife 2017, 6:e20994. doi: 10.7554/eLife.20994

    25.    He Xu, Chunmei Yue, Ting Zhang, Yuanyuan Li, Ao Guo, Jiaoyang Liao, Gang Pei, Jinsong Li*, Naihe Jing*. Derivation of haploid neurons from mouse androgenetic haploid embryonic stem cells. Neurosci Bull 2017, 33:361-364. doi: 10.1007/s12264-017-0110-9

    26.    Guangdun Peng* and Naihe Jing*. The genome-wide molecular regulation of mouse gastrulation embryo. SCIENCE CHINA Life Sciences 2017, 60:363-369. doi: 10.1007/s11427-016-0285-3 (Review)

    27.    Lingbo Wang, Min-Yin Li, Chao Qu, Wan-Ying Miao, Qi Yin, Jiaoyang Liao, Hua-Teng Cao, Min Huang, Kai Wang, Erwei Zuo, Guangdun Peng, Shu-Xin Zhang, Guodong Chen, Qing Li, Ke Tang, Qian Yu, Zhoujie Li, Catherine CL Wong, Guoliang Xu, Naihe Jing, Xiang Yu*, Jinsong Li*. CRISPR-Cas9-mediated genome editing in one blastomere of two-cell embryos reveals a novel Tet3 function in regulating neocortical development. Cell Research 2017; 27:815-829. doi:10.1038/cr.2017.58.

    28.    Guangdun Peng, Patrick Tam, Naihe Jing*. Lineage specification of early embryos and embryonic stem cells at the dawn of enabling technologies. National Science Review 2017, 4:533-542. (Review)

    29.    Rui Lu, Junfeng Wang, Ran Tao, Jun Wang, Ting Zhu, Wenke Guo, Yimin Sun, Honglei Li, Yuan Gao, Wei Zhang, Christopher J. Fowler, Qiaoxin Li, Shengdi Chen, Zhiying Wu, Colin L. Masters, Chunjiu Zhong, Naihe Jing, Yanjiang Wang and Yizheng Wang*. Reduced TRPC6 mRNA levels in the blood cells of patients with Alzheimer’s disease and mild cognitive impairment. Molecular Psychiatry 2017, doi:10.1038/mp.2017.136

    30.    Su Feng, Can Xing, Tingyu Shen, Yunbo Qiao, Ran Wang, Jun Chen, Jiaoyang Liao, Zhuo Lu, Xiong Yang, Saber Mohamed Abd-Allah, Jinsong Li, Naihe Jing* & Ke Tang*. Abnormal paraventricular nucleus of hypothalamus and growth retardation associated with loss of nuclear receptor gene COUP-TFII. Scientific Reports 2017, doi:10.1038/s41598-017-05682-6

    31.    Yuanyuan Li, Ran Wang, Nan Qiao, Guangdun Peng, Ke Zhang, Ke Tang, Jing-Dong J Han and Naihe Jing*. Transcriptome analysis reveals determinant stages controlling human embryonic stem cell commitment to neuronal cells. J Biol Chem 2017, doi:10.1074/jbc.M117.796383

    32.    Chang Liu, Guangdun Peng and Naihe Jing*. TGF-β signaling pathway in early mouse development and embryonic stem cells. Acta Biochimica et Biophysica Sinica 2018, 50:68-73, doi: 10.1093/abbs/gmx120 (Review)

    33.    Na Sun, Xiaoming Yu, Fang Li, Denghui Liu, Shengbao Suo, Weiyang Chen, Shirui Chen, Lu Song, Christopher Green, Joseph McDermott, Qin Shen, Naihe Jing and Jing-Dong Han*. Inference of differentiation time for single cell transcriptomes using cell population reference data. Nature Communications 2017, doi: 10.1038/s41467-017-01860-2

    34.    Xianfa Yang, Boqiang Hu, Yu Hou3, Yunbo Qiao, Ran Wang, Yingying Chen, Yun Qian, Su Feng, Jun Chen, Chang Liu, Guangdun Peng, Fuchou Tang* and Naihe Jing*. Epigenetic silencing of developmental genes by H3K27me3 and DNA methylation in mouse post-implantation embryos reflects the discrepant plasticity of extraembryonic and embryonic lineages. Cell Research 2018, 18, 593-596 doi.org/10.1038/s41422-018

    35.    Xue Han, Sai Luo, Guangdun Peng, J Yuyang Lu, Guizhong Cui, Lichao Liu, Pixi Yan, Yafei Yin, Wei Liu, Ran Wang, Zai Chang, Jie Na, Naihe Jing*, and Xiaohua Shen*. Mouse knockout models reveal largely dispensable but context-dependent functions of lncRNAs during development. J Mol Cell Biol 2018, 10, 175-178 doi/10.1093/jmcb/mjy003/4840688

    36.    Xianfa Yang, Ran Wang, Xiongjun Wang, Guoqing Cai, Yun Qian, Su Feng, Fangzhi Tan, Kun Chen, Ke Tang, Xingxu Huang, Naihe Jing*, and Yunbo Qiao*. TGFb signaling hyperactivation-induced tumorigenicity during the derivation of neural progenitors from mouse ESCs. J Mol Cell Biol 2018,10, 216-228 doi:10.1093/jmcb/mjy013

    37.    Chang Liu, Ran Wang, Zhisong He, Pierre Osteil, Emilie Wilkie, Xianfa Yang, Guangdun Peng, Jun Chen, Patrick P.L. Tam and Naihe Jing*. Suppressing nodal signaling activity predisposes ectodermal differentiation of epiblast stem cells. Stem Cell Reports 2018, doi.org/10.1016/j.stemcr.2018.05.019

    38.    Berna Sozen, Gianluca Amadei, Andy Cox, Ran Wang, Ellen Na, Sylwia Czukiewska, Lia Chappell, Thierry Voet, Geert Michel, Naihe Jing, David M. Glover and Magdalena Zernicka-Goetz*. Self-assembly of embryonic and two extraembryonic stem cell types into gastrulating embryo-like structures. Nature Cell Biology, 2018, 20, 979-989 doi.org/10.1038/s41556-018-0147-7

    39.    Tennille Sibbritt, Chi K. Ip, PohLynn Khoo, Emilie Wilkie, Vanessa Jones, Jane Q. J. Sun, Joanne X. Shen, Guangdun Peng, Jing-Dong J. Han, Naihe Jing, Pierre Osteil, Mirana Ramialison, Patrick P. L. Tam, Nicolas Fossat*. A gene regulatory network anchored by LIM homeobox 1 for embryonic head development. Genesis, 2018, doi.org/10.1002/dvg.23246

    40.    Clayton E. Friedman, Quan Nguyen, Samuel W. Lukowski, Abbigail Helfer, Han Sheng Chiu, Jason Miklas, Shiri Levy, Shengbao Suo, Jing-Dong Jackie Han, Pierre Osteil, Guangdun Peng, Naihe Jing, Greg J. Baillie, Anne Senabouth, Angelika N. Christ, Timothy J. Bruxner, Charles E. Murry, Emily S. Wong, Jun Ding, Yuliang Wang, James Hudson, Hannele Ruohola-Baker, Ziv Bar-Joseph, Patrick P.L. Tam, Joseph E. Powell*, and Nathan J. Palpant*. Single-cell transcriptomic analysis of cardiac differentiation from human PSCs reveals HOPX-dependent cardiomyocyte maturation. Cell Stem Cell, 2018, 23, 586–598, doi.org/10.1016/j.stem.2018.09.009

    41.    Neophytos Christodoulou, Christos Kyprianou, Antonia Weberling, Ran Wang, Guizhong Cui, Guangdun Peng, Naihe Jing, and Magdalena Zernicka-Goetz*. Sequential formation and resolution of multiple rosettes drives embryo remodeling after implantation. Nature Cell Biology, 2018, 20, 1278-1289

    42.    Guangdun Peng, Shengbao Suo, Guizhong Cui, Ran Wang, Jing-Dong J. Han*, Patrick P L Tam*, Naihe Jing*. Mouse gastrulation: attributes of transcriptional factor regulatory network for embryonic patterning. Development Growth and Differentiation, 2018, 60, 463-472

    43.    Yu, W., Ma, X., Xu, J., Heumüller, A.W., Fei, Z., Feng, X., Wang, X., Liu, K., Li, J., Cui, G., Peng, G., Ji, H., Li, J., Jing, N., Song, H., Lin, Z., Zhao, Y., Wang, Z., Zhou, B. and Zhang, L. (2019) VGLL4 plays a critical role in heart valve development and homeostasis. PLoS Genet 15, e1007977.

    44.    Cui, G., Chen, J., Chen, S., Qian, Y., Peng, G. and Jing, N. (2019) Spatio-temporal transcriptome construction of early mouse embryo with Geo-seq and Auto-seq. Protocol Exchange

    45.    Fang, Z., Liu, X., Wen, J., Tang, F., Zhou, Y., Jing, N. and Jin, Y. (2019) SOX21 Ensures Rostral Forebrain Identity by Suppression of WNT8B during Neural Regionalization of Human Embryonic Stem Cells. Stem Cell Reports 13, 1038-1052.

    46.    Cheng, S., Pei, Y., He, L., Peng, G., Reinius, B., Tam, P.P.L., Jing, N. and Deng, Q. (2019) Single-Cell RNA-Seq Reveals Cellular Heterogeneity of Pluripotency Transition and X Chromosome Dynamics during Early Mouse Development. Cell Rep 26, 2593-2607.e3.

    47.    Xiao, Y., Chen, J., Wan, Y., Gao, Q., Jing, N., Zheng, Y. and Zhu, X. (2019) Regulation of zebrafish dorsoventral patterning by phase separation of RNA-binding protein Rbm14. Cell Discov 5, 37.

    48.    Peng, G.*, Suo, S., Cui, G., Yu, F., Wang, R., Chen, J., Chen, S., Liu, Z., Chen, G., Qian, Y., Tam, P.P.L., Han, J.J.* and Jing, N*. (2019) Molecular architecture of lineage allocation and tissue organization in early mouse embryo. Nature 572, 528-532.

    49.    Liu, Q., Liu, K., Cui, G., Huang, X., Yao, S., Guo, W., Qin, Z., Li, Y., Yang, R., Pu, W., Zhang, L., He, L., Zhao, H., Yu, W., Tang, M., Tian, X., Cai, D., Nie, Y., Hu, S., Ren, T., Qiao, Z., Huang, H., Zeng, Y.A., Jing, N., Peng, G., Ji, H. and Zhou, B. (2019) Lung regeneration by multipotent stem cells residing at the bronchioalveolar-duct junction. Nat Genet 51, 728-738.

    50.    Zhang, T., Ke, W., Zhou, X., Qian, Y., Feng, S., Wang, R., Cui, G., Tao, R., Guo, W., Duan, Y., Zhang, X., Cao, X., Shu, Y., Yue, C. and Jing, N.* (2019) Human Neural Stem Cells Reinforce Hippocampal Synaptic Network and Rescue Cognitive Deficits in a Mouse Model of Alzheimer’s Disease. Stem Cell Reports 13, 1022-1037.

    51.    Song, W., Wang, R., Jiang, W., Yin, Q., Peng, G., Yang, R., Yu, Q.C., Chen, J., Li, J., Cheung, T.H., Jing, N. and Zeng, Y.A. (2019) Hormones induce the formation of luminal-derived basal cells in the mammary gland. Cell Res 29, 206-220.

    52.    Osteil, P., Studdert, J.B., Goh, H.N., Wilkie, E.E., Fan, X., Khoo, P.L., Peng, G., Salehin, N., Knowles, H., Han, J.J., Jing, N., Fossat, N. and Tam, P.P.L. (2019) Dynamics of Wnt activity on the acquisition of ectoderm potency in epiblast stem cells. Development 146,

    53.    Yang, X., Hu, B., Liao, J., Qiao, Y., Chen, Y., Qian, Y., Feng, S., Yu, F., Dong, J., Hou, Y., Xu, H., Wang, R., Peng, G., Li, J., Tang, F. and Jing, N. (2019) Distinct enhancer signatures in the mouse gastrula delineate progressive cell fate continuum during embryo development. Cell Res 29, 911-926.

    54.    Cui, G., Jing, N. and Peng, G. (2019) Comments on ‘Molecular architecture of lineage allocation and tissue organization in early mouse embryo’. J Mol Cell Biol 11, 1024-1025.

    55.    Zhou, Y., Wang, X., Song, M., He, Z., Cui, G., Peng, G., Dieterich, C., Antebi, A., Jing, N. and Shen, Y. (2019) A secreted microRNA disrupts autophagy in distinct tissues of Caenorhabditis elegans upon ageing. Nat Commun 10, 4827.

    56.    Xue, Y., Liu, D., Cui, G., Ding, Y., Ai, D., Gao, S., Zhang, Y., Suo, S., Wang, X., Lv, P., Zhou, C., Li, Y., Chen, X., Peng, G., Jing, N., Han, J.J. and Liu, F. (2019) A 3D Atlas of Hematopoietic Stem and Progenitor Cell Expansion by Multi-dimensional RNA-Seq Analysis. Cell Rep 27, 1567-1578.e5.