Identification of Transcription Factors for Lineage-Specific ESC Differentiation

被引：65
作者：
Yamamizu, Kohei [1 ]
Piao, Yulan [1 ]
Sharov, Alexei A. [1 ]
Zsiros, Veronika [2 ]
Yu, Hong [1 ]
Nakazawa, Kazu [2 ]
Schlessinger, David [1 ]
Ko, Minoru S. H. [1 ,3 ,4 ]
机构：
[1] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA
[2] NIMH, Unit Genet Cognit & Behav, NIH, Bethesda, MD 20892 USA
[3] Keio Univ, Dept Syst Med, Sch Med, Sakaguchi Lab, Tokyo 1608582, Japan
[4] Japan Sci & Technol Agcy, CREST, Tokyo 1608528, Japan
来源：
STEM CELL REPORTS | 2013年 / 1卷 / 06期
基金：
日本科学技术振兴机构;
关键词：
EMBRYONIC STEM-CELLS; COUP-TFI; DIRECT CONVERSION; HUMAN FIBROBLASTS; DEFINED FACTORS; MOUSE EMBRYOS; GENE; EXPRESSION; RECEPTOR; NEURONS;
D O I：
10.1016/j.stemcr.2013.10.006
中图分类号：
Q813 [细胞工程];
学科分类号：
摘要：
A network of transcription factors (TFs) determines cell identity, but identity can be altered by overexpressing a combination of TFs. However, choosing and verifying combinations of TFs for specific cell differentiation have been daunting due to the large number of possible combinations of similar to 2,000 TFs. Here, we report the identification of individual TFs for lineage-specific cell differentiation based on the correlation matrix of global gene expression profiles. The overexpression of identified TFs-Myod1, Mef2c, Esx1, Foxa1, Hnf4a, Gata2, Gata3, Myc, Elf5, Irf2, Elf1, Sfpi1, Ets1, Smad7, Nr2f1, Sox11, Dmrt1, Sox9, Foxg1, Sox2, or Ascl1-can direct efficient, specific, and rapid differentiation into myocytes, hepatocytes, blood cells, and neurons. Furthermore, transfection of synthetic mRNAs of TFs generates their appropriate target cells. These results demonstrate both the utility of this approach to identify potent TFs for cell differentiation, and the unanticipated capacity of single TFs directly guides differentiation to specific lineage fates.
引用
收藏
页码：545 / 559
页数：15
相关论文
共 58 条
[1]   Defining a developmental path to neural fate by global expression profiling of mouse embryonic stem cells and adult neural stem/progenitor cells [J].
Aiba, Kazuhiro ;
Sharov, Alexei A. ;
Carter, Mark G. ;
Foroni, Chiara ;
Vescovi, Angelo L. ;
Ko, Minoru S. H. .
STEM CELLS, 2006, 24 (04) :889-895
[2]   Defining Developmental Potency and Cell Lineage Trajectories by Expression Profiling of Differentiating Mouse Embryonic Stem Cells [J].
Aiba, Kazuhiro ;
Nedorezov, Timur ;
Piao, Yulan ;
Nishiyama, Akira ;
Matoba, Ryo ;
Sharova, Lioudmila V. ;
Sharov, Alexei A. ;
Yamanaka, Shinya ;
Niwa, Hitoshi ;
Ko, Minoru S. H. .
DNA RESEARCH, 2009, 16 (01) :73-80
[3]   COUP-TFI promotes radial migration and proper morphology of callosal projection neurons by repressing Rnd2 expression [J].
Alfano, Christian ;
Viola, Luigi ;
Heng, Julian Ik-Tsen ;
Pirozzi, Marinella ;
Clarkson, Michael ;
Flore, Gemma ;
De Maio, Antonia ;
Schedl, Andreas ;
Guillemot, Francois ;
Studer, Michele .
DEVELOPMENT, 2011, 138 (21) :4685-4697
[4]   PU.1 is a lineage-specific regulator of tyrosine phosphatase CD45 [J].
Anderson, KL ;
Nelson, SL ;
Perkin, HB ;
Smith, KA ;
Klemsz, MJ ;
Torbett, BE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (10) :7637-7642
[5]   Role of Sox2 in the development of the mouse neocortex [J].
Bani-Yaghoub, Mahmud ;
Tremblay, Roger G. ;
Lei, Joy X. ;
Zhang, Dongling ;
Zurakowski, Bogdan ;
Sandhu, Jagdeep K. ;
Smith, Brandon ;
Ribecco-Lutkiewicz, Maria ;
Kennedy, Jessica ;
Walker, P. Roy ;
Sikorska, Marianna .
DEVELOPMENTAL BIOLOGY, 2006, 295 (01) :52-66
[6]   Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes [J].
Belforte, Juan E. ;
Zsiros, Veronika ;
Sklar, Elyse R. ;
Jiang, Zhihong ;
Yu, Gu ;
Li, Yuqing ;
Quinlan, Elizabeth M. ;
Nakazawa, Kazu .
NATURE NEUROSCIENCE, 2010, 13 (01) :76-U240
[7]   Transcriptional regulation of the stem cell leukemia gene by PU.1 and Elf-1 [J].
Bockamp, EO ;
Fordham, JL ;
Göttgens, B ;
Murrell, AM ;
Sanchez, MJ ;
Green, AR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (44) :29032-29042
[8]   Direct generation of functional dopaminergic neurons from mouse and human fibroblasts [J].
Caiazzo, Massimiliano ;
Dell'Anno, Maria Teresa ;
Dvoretskova, Elena ;
Lazarevic, Dejan ;
Taverna, Stefano ;
Leo, Damiana ;
Sotnikova, Tatyana D. ;
Menegon, Andrea ;
Roncaglia, Paola ;
Colciago, Giorgia ;
Russo, Giovanni ;
Carninci, Piero ;
Pezzoli, Gianni ;
Gainetdinov, Raul R. ;
Gustincich, Stefano ;
Dityatev, Alexander ;
Broccoli, Vania .
NATURE, 2011, 476 (7359) :224-U151
[9]   Proneural bHLH and Brn proteins coregulate a neurogenic program through cooperative binding to a conserved DNA motif [J].
Castro, Diogo S. ;
Skowronska-Krawczyk, Dorota ;
Armant, Olivier ;
Donaldson, Ian J. ;
Parras, Carlos ;
Hunt, Charles ;
Critchley, James A. ;
Nguyen, Laurent ;
Gossler, Achim ;
Goettgens, Berthold ;
Matter, Jean-Marc ;
Guillemot, Francois .
DEVELOPMENTAL CELL, 2006, 11 (06) :831-844
[10]   Differential requirements for the Ets transcription factor Elf-1 in the development of NKT cells and NK cells [J].
Choi, Hak-Jong ;
Geng, Yanbiao ;
Cho, Hoonsik ;
Li, Sha ;
Giri, Pramod Kumar ;
Felio, Kyrie ;
Wang, Chyung-Ru .
BLOOD, 2011, 117 (06) :1880-1887
123456