Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors

Jongpil Kim, Christopher J. Lengner, Oktay Kirak, Jacob Hanna, John P. Cassady, Michael A. Lodato, S. U. Wu, Dina A. Faddah, Eveline J. Steine, G. A O Qing, Dongdong Fu, Meelad M. Dawlaty, Rudolf Jaenisch

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)992-1000
Number of pages9
JournalStem Cells
Volume29
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

Fingerprint

Induced Pluripotent Stem Cells
Stem Cell Factor
Neurons
Transcriptional Silencer Elements
Genetic Epigenesis
Suppressor Genes
Epigenomics
Transcription Factors
Cell Proliferation
Gene Expression
Ectopic Gene Expression
Cellular Reprogramming

Keywords

  • Induced pluripotency
  • Neuron
  • p53
  • Pluripotent stem cells
  • Reprogramming

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Kim, J., Lengner, C. J., Kirak, O., Hanna, J., Cassady, J. P., Lodato, M. A., ... Jaenisch, R. (2011). Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors. Stem Cells, 29(6), 992-1000. https://doi.org/10.1002/stem.641

Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors. / Kim, Jongpil; Lengner, Christopher J.; Kirak, Oktay; Hanna, Jacob; Cassady, John P.; Lodato, Michael A.; Wu, S. U.; Faddah, Dina A.; Steine, Eveline J.; Qing, G. A O; Fu, Dongdong; Dawlaty, Meelad M.; Jaenisch, Rudolf.

In: Stem Cells, Vol. 29, No. 6, 06.2011, p. 992-1000.

Research output: Contribution to journalArticle

Kim, J, Lengner, CJ, Kirak, O, Hanna, J, Cassady, JP, Lodato, MA, Wu, SU, Faddah, DA, Steine, EJ, Qing, GAO, Fu, D, Dawlaty, MM & Jaenisch, R 2011, 'Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors', Stem Cells, vol. 29, no. 6, pp. 992-1000. https://doi.org/10.1002/stem.641
Kim J, Lengner CJ, Kirak O, Hanna J, Cassady JP, Lodato MA et al. Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors. Stem Cells. 2011 Jun;29(6):992-1000. https://doi.org/10.1002/stem.641
Kim, Jongpil ; Lengner, Christopher J. ; Kirak, Oktay ; Hanna, Jacob ; Cassady, John P. ; Lodato, Michael A. ; Wu, S. U. ; Faddah, Dina A. ; Steine, Eveline J. ; Qing, G. A O ; Fu, Dongdong ; Dawlaty, Meelad M. ; Jaenisch, Rudolf. / Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors. In: Stem Cells. 2011 ; Vol. 29, No. 6. pp. 992-1000.
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