Reprogramming of Postnatal Neurons into Induced Pluripotent Stem Cells by Defined Factors

被引:47
|
作者
Kim, Jongpil [1 ]
Lengner, Christopher J. [1 ]
Kirak, Oktay [1 ]
Hanna, Jacob [1 ]
Cassady, John P. [1 ,2 ]
Lodato, Michael A. [1 ,2 ]
Wu, Su [1 ]
Faddah, Dina A. [1 ,2 ]
Steine, Eveline J. [1 ]
Gao, Qing [1 ]
Fu, Dongdong [1 ]
Dawlaty, Meelad [1 ]
Jaenisch, Rudolf [1 ,2 ]
机构
[1] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA
[2] MIT, Dept Biol, Cambridge, MA USA
基金
美国国家卫生研究院;
关键词
Neuron; Reprogramming; Pluripotent stem cells; p53; Induced pluripotency; SOMATIC-CELLS; GENERATION; PATHWAY; FIBROBLASTS; EXPRESSION;
D O I
10.1002/stem.641
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Pluripotent cells can be derived from different types of somatic cells by nuclear reprogramming through the ectopic expression of four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc. However, it is unclear whether postmitotic neurons are susceptible to direct reprogramming. Here, we show that postnatal cortical neurons, the vast majority of which are postmitotic, are amenable to epigenetic reprogramming. However, ectopic expression of the four canonical reprogramming factors is not sufficient to reprogram postnatal neurons. Efficient reprogramming was only achieved after forced cell proliferation by p53 suppression. Additionally, overexpression of repressor element-1 silencing transcription, a suppressor of neuronal gene activity, increased reprogramming efficiencies in combination with the reprogramming factors. Our findings indicate that terminally differentiated postnatal neurons are able to acquire the pluripotent state by direct epigenetic reprogramming, and this process is made more efficient through the suppression of lineage specific gene expression. STEM CELLS 2011;29:992-1000
引用
收藏
页码:992 / 1000
页数:9
相关论文
共 50 条
  • [21] Avian-Induced Pluripotent Stem Cells Derived Using Human Reprogramming Factors
    Lu, Yangqing
    West, Franklin D.
    Jordan, Brian J.
    Mumaw, Jennifer L.
    Jordan, Erin T.
    Gallegos-Cardenas, Amalia
    Beckstead, Robert B.
    Stice, Steven L.
    STEM CELLS AND DEVELOPMENT, 2012, 21 (03) : 394 - 403
  • [22] Reprogramming of adult human neural stem cells into induced pluripotent stem cells
    Xie Li-qian
    Sun Hua-ping
    Wang Tian
    Tang Hai-liang
    Wang Pu
    Zhu Jian-hong
    Yao Zheng-wei
    Feng Xiao-yuan
    CHINESE MEDICAL JOURNAL, 2013, 126 (06) : 1138 - 1143
  • [23] GENERATION OF INDUCED PLURIPOTENT STEM CELLS FROM BOVINE FETAL FIBROBLAST CELLS BY DEFINED FACTORS
    Cao, H. G.
    Liu, Y.
    Yin, H. Q.
    Sun, X. P.
    Li, Y. S.
    Tao, Y.
    Zhang, Y. H.
    Zhang, X. R.
    REPRODUCTION FERTILITY AND DEVELOPMENT, 2011, 23 (01) : 243 - 243
  • [24] Reprogramming of Human Peripheral Blood Cells to Induced Pluripotent Stem Cells
    Staerk, Judith
    Dawlaty, Meelad M.
    Gao, Qing
    Maetzel, Dorothea
    Hanna, Jacob
    Sommer, Cesar A.
    Mostoslavsky, Gustavo
    Jaenisch, Rudolf
    CELL STEM CELL, 2010, 7 (01) : 20 - 24
  • [25] Improving the Reprogramming Efficiency of Somatic Cells to Induced Pluripotent Stem Cells
    Hu, Chen-Xia
    Li, Lan-Juan
    CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION, 2015, 25 (04): : 323 - 334
  • [26] Bovine trophectoderm cells induced from bovine fibroblasts with induced pluripotent stem cell reprogramming factors
    Talbot, Neil C.
    Sparks, Wendy O.
    Phillips, Caitlin E.
    Ealy, Alan D.
    Powell, Anne M.
    Caperna, Thomas J.
    Garrett, Wesley M.
    Donovan, David M.
    Blomberg, Le Ann
    MOLECULAR REPRODUCTION AND DEVELOPMENT, 2017, 84 (06) : 468 - 485
  • [27] Reprogramming of mouse fibroblasts into induced pluripotent stem cells with Nanog
    Moon, Jai-Hee
    Yun, Wonjin
    Kim, Jihyun
    Hyeon, Solji
    Kang, Phil Jun
    Park, Gyuman
    Kim, Aeree
    Oh, Sejong
    Whang, Kwang Youn
    Kim, Dong-Wook
    Yoon, Byung Sun
    You, Seungkwon
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2013, 431 (03) : 444 - 449
  • [28] Chromosomal aberrations after induced pluripotent stem cells reprogramming
    Vaz, Isadora May
    Borgonovo, Tamara
    Kasai-Brunswick, Tais Hanae
    dos Santos, Danubia Silva
    Paccola Mesquita, Fernanda Cristina
    Vasques, Juliana Ferreira
    Gubert, Fernanda
    Kuniyoshi Rebelatto, Carmen Lucia
    Senegaglia, Alexandra Cristina
    Slud Brofman, Paulo Roberto
    GENETICS AND MOLECULAR BIOLOGY, 2021, 44 (03)
  • [29] Advancements in reprogramming strategies for the generation of induced pluripotent stem cells
    Lai, Mei I.
    Wendy-Yeo, Wai Yeng
    Ramasamy, Rajesh
    Nordin, Norshariza
    Rosli, Rozita
    Veerakumarasivam, Abhi
    Abdullah, Syahril
    JOURNAL OF ASSISTED REPRODUCTION AND GENETICS, 2011, 28 (04) : 291 - 301
  • [30] Induced pluripotent stem cells (iPSCs)-a new era of reprogramming
    Kang, Lan
    Kou, Zhaohui
    Zhang, Yu
    Gao, Shaorong
    JOURNAL OF GENETICS AND GENOMICS, 2010, 37 (07) : 415 - 421