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
机构:
Whitehead Inst Biomed Res, Cambridge, MA 02142 USAWhitehead Inst Biomed Res, Cambridge, MA 02142 USA
Staerk, Judith
Dawlaty, Meelad M.
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Whitehead Inst Biomed Res, Cambridge, MA 02142 USAWhitehead Inst Biomed Res, Cambridge, MA 02142 USA
Dawlaty, Meelad M.
Gao, Qing
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Whitehead Inst Biomed Res, Cambridge, MA 02142 USAWhitehead Inst Biomed Res, Cambridge, MA 02142 USA
Gao, Qing
Maetzel, Dorothea
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Whitehead Inst Biomed Res, Cambridge, MA 02142 USAWhitehead Inst Biomed Res, Cambridge, MA 02142 USA
Maetzel, Dorothea
Hanna, Jacob
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机构:
Whitehead Inst Biomed Res, Cambridge, MA 02142 USAWhitehead Inst Biomed Res, Cambridge, MA 02142 USA
Hanna, Jacob
Sommer, Cesar A.
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机构:
Boston Univ, Sch Med, Dept Med, Gastroenterol Sect, Boston, MA 02118 USA
Boston Univ, Sch Med, Ctr Regenerat Med CReM, Boston, MA 02118 USAWhitehead Inst Biomed Res, Cambridge, MA 02142 USA
Sommer, Cesar A.
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Mostoslavsky, Gustavo
Jaenisch, Rudolf
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h-index: 0
机构:
Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
MIT, Dept Biol, Cambridge, MA 02139 USAWhitehead Inst Biomed Res, Cambridge, MA 02142 USA
机构:
Korea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South KoreaKorea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South Korea
Moon, Jai-Hee
Yun, Wonjin
论文数: 0引用数: 0
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机构:
Korea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South KoreaKorea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South Korea
Yun, Wonjin
Kim, Jihyun
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Korea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South KoreaKorea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South Korea
Kim, Jihyun
Hyeon, Solji
论文数: 0引用数: 0
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机构:
Korea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South KoreaKorea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South Korea
Hyeon, Solji
Kang, Phil Jun
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Korea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South KoreaKorea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South Korea
Kang, Phil Jun
Park, Gyuman
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Korea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South KoreaKorea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South Korea
Park, Gyuman
Kim, Aeree
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机构:
Korea Univ, Coll Med, Guro Hosp, Dept Pathol, Seoul 136705, South KoreaKorea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South Korea
Kim, Aeree
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Oh, Sejong
Whang, Kwang Youn
论文数: 0引用数: 0
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机构:
Korea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Seoul, South KoreaKorea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South Korea
Whang, Kwang Youn
Kim, Dong-Wook
论文数: 0引用数: 0
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机构:
Yonsei Univ, Coll Med, Dept Physiol, Ctr Cell Therapy, Seoul, South KoreaKorea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South Korea
Kim, Dong-Wook
Yoon, Byung Sun
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Korea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South KoreaKorea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South Korea
Yoon, Byung Sun
You, Seungkwon
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Korea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South KoreaKorea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Cell Funct Regulat, Seoul, South Korea
机构:
Pontificia Univ Catolica Parana, Nucleo Tecnol Celular, Escola Med, Curitiba, Parana, Brazil
Inst Nacl Ciencia & Tecnol Med Regenerat, Rio De Janeiro, RJ, BrazilPontificia Univ Catolica Parana, Nucleo Tecnol Celular, Escola Med, Curitiba, Parana, Brazil
Vaz, Isadora May
Borgonovo, Tamara
论文数: 0引用数: 0
h-index: 0
机构:
Pontificia Univ Catolica Parana, Nucleo Tecnol Celular, Escola Med, Curitiba, Parana, Brazil
Inst Nacl Ciencia & Tecnol Med Regenerat, Rio De Janeiro, RJ, BrazilPontificia Univ Catolica Parana, Nucleo Tecnol Celular, Escola Med, Curitiba, Parana, Brazil
Borgonovo, Tamara
Kasai-Brunswick, Tais Hanae
论文数: 0引用数: 0
h-index: 0
机构:
Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Rio De Janeiro, RJ, Brazil
Univ Fed Rio de Janeiro, Ctr Nacl Biol Estrutural & Bioimagem, Rio De Janeiro, RJ, BrazilPontificia Univ Catolica Parana, Nucleo Tecnol Celular, Escola Med, Curitiba, Parana, Brazil
Kasai-Brunswick, Tais Hanae
dos Santos, Danubia Silva
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机构:
Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Rio De Janeiro, RJ, BrazilPontificia Univ Catolica Parana, Nucleo Tecnol Celular, Escola Med, Curitiba, Parana, Brazil
dos Santos, Danubia Silva
Paccola Mesquita, Fernanda Cristina
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Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Rio De Janeiro, RJ, BrazilPontificia Univ Catolica Parana, Nucleo Tecnol Celular, Escola Med, Curitiba, Parana, Brazil
Paccola Mesquita, Fernanda Cristina
Vasques, Juliana Ferreira
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机构:
Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Rio De Janeiro, RJ, Brazil
Inst Nacl Ciencia & Tecnol Med Regenerat, Rio De Janeiro, RJ, BrazilPontificia Univ Catolica Parana, Nucleo Tecnol Celular, Escola Med, Curitiba, Parana, Brazil
Vasques, Juliana Ferreira
Gubert, Fernanda
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机构:
Inst Nacl Ciencia & Tecnol Med Regenerat, Rio De Janeiro, RJ, Brazil
Inst Ciencias Biomed, Rio De Janeiro, RJ, BrazilPontificia Univ Catolica Parana, Nucleo Tecnol Celular, Escola Med, Curitiba, Parana, Brazil
Gubert, Fernanda
Kuniyoshi Rebelatto, Carmen Lucia
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机构:
Pontificia Univ Catolica Parana, Nucleo Tecnol Celular, Escola Med, Curitiba, Parana, Brazil
Inst Nacl Ciencia & Tecnol Med Regenerat, Rio De Janeiro, RJ, BrazilPontificia Univ Catolica Parana, Nucleo Tecnol Celular, Escola Med, Curitiba, Parana, Brazil
Kuniyoshi Rebelatto, Carmen Lucia
Senegaglia, Alexandra Cristina
论文数: 0引用数: 0
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机构:
Pontificia Univ Catolica Parana, Nucleo Tecnol Celular, Escola Med, Curitiba, Parana, Brazil
Inst Nacl Ciencia & Tecnol Med Regenerat, Rio De Janeiro, RJ, BrazilPontificia Univ Catolica Parana, Nucleo Tecnol Celular, Escola Med, Curitiba, Parana, Brazil
Senegaglia, Alexandra Cristina
Slud Brofman, Paulo Roberto
论文数: 0引用数: 0
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机构:
Pontificia Univ Catolica Parana, Nucleo Tecnol Celular, Escola Med, Curitiba, Parana, Brazil
Inst Nacl Ciencia & Tecnol Med Regenerat, Rio De Janeiro, RJ, BrazilPontificia Univ Catolica Parana, Nucleo Tecnol Celular, Escola Med, Curitiba, Parana, Brazil
机构:
Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Pathol, Serdang Upm 43400, Selangor, Malaysia
Univ Putra Malaysia, Fac Med & Hlth Sci, Stem Cell Res Lab, Serdang Upm 43400, Selangor, MalaysiaUniv Putra Malaysia, Fac Med & Hlth Sci, Med Genet Lab, Clin Genet Unit,UPM, Serdang 43400, Selangor, Malaysia
Lai, Mei I.
Wendy-Yeo, Wai Yeng
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机构:
Univ Putra Malaysia, Fac Med & Hlth Sci, Med Genet Lab, Clin Genet Unit,UPM, Serdang 43400, Selangor, Malaysia
Univ Putra Malaysia, UPM MAKNA Canc Res Lab, Inst Biosci, Serdang Upm 43400, Selangor, MalaysiaUniv Putra Malaysia, Fac Med & Hlth Sci, Med Genet Lab, Clin Genet Unit,UPM, Serdang 43400, Selangor, Malaysia
Wendy-Yeo, Wai Yeng
Ramasamy, Rajesh
论文数: 0引用数: 0
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机构:
Univ Putra Malaysia, UPM MAKNA Canc Res Lab, Inst Biosci, Serdang Upm 43400, Selangor, Malaysia
Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Pathol, Serdang Upm 43400, Selangor, MalaysiaUniv Putra Malaysia, Fac Med & Hlth Sci, Med Genet Lab, Clin Genet Unit,UPM, Serdang 43400, Selangor, Malaysia
Ramasamy, Rajesh
Nordin, Norshariza
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h-index: 0
机构:
Univ Putra Malaysia, Fac Med & Hlth Sci, Med Genet Lab, Clin Genet Unit,UPM, Serdang 43400, Selangor, Malaysia
Univ Putra Malaysia, Fac Med & Hlth Sci, Stem Cell Res Lab, Serdang Upm 43400, Selangor, MalaysiaUniv Putra Malaysia, Fac Med & Hlth Sci, Med Genet Lab, Clin Genet Unit,UPM, Serdang 43400, Selangor, Malaysia
Nordin, Norshariza
Rosli, Rozita
论文数: 0引用数: 0
h-index: 0
机构:
Univ Putra Malaysia, Fac Med & Hlth Sci, Med Genet Lab, Clin Genet Unit,UPM, Serdang 43400, Selangor, Malaysia
Univ Putra Malaysia, UPM MAKNA Canc Res Lab, Inst Biosci, Serdang Upm 43400, Selangor, MalaysiaUniv Putra Malaysia, Fac Med & Hlth Sci, Med Genet Lab, Clin Genet Unit,UPM, Serdang 43400, Selangor, Malaysia
Rosli, Rozita
Veerakumarasivam, Abhi
论文数: 0引用数: 0
h-index: 0
机构:
Univ Putra Malaysia, Fac Med & Hlth Sci, Med Genet Lab, Clin Genet Unit,UPM, Serdang 43400, Selangor, Malaysia
Perdana Univ, Grad Sch Med, Serdang 43400, Selangor, MalaysiaUniv Putra Malaysia, Fac Med & Hlth Sci, Med Genet Lab, Clin Genet Unit,UPM, Serdang 43400, Selangor, Malaysia
Veerakumarasivam, Abhi
Abdullah, Syahril
论文数: 0引用数: 0
h-index: 0
机构:
Univ Putra Malaysia, Fac Med & Hlth Sci, Med Genet Lab, Clin Genet Unit,UPM, Serdang 43400, Selangor, Malaysia
Univ Putra Malaysia, UPM MAKNA Canc Res Lab, Inst Biosci, Serdang Upm 43400, Selangor, MalaysiaUniv Putra Malaysia, Fac Med & Hlth Sci, Med Genet Lab, Clin Genet Unit,UPM, Serdang 43400, Selangor, Malaysia