Publication Date:
2011-05-28
Description:
Somatic cell nuclear transfer, cell fusion, or expression of lineage-specific factors have been shown to induce cell-fate changes in diverse somatic cell types. We recently observed that forced expression of a combination of three transcription factors, Brn2 (also known as Pou3f2), Ascl1 and Myt1l, can efficiently convert mouse fibroblasts into functional induced neuronal (iN) cells. Here we show that the same three factors can generate functional neurons from human pluripotent stem cells as early as 6 days after transgene activation. When combined with the basic helix-loop-helix transcription factor NeuroD1, these factors could also convert fetal and postnatal human fibroblasts into iN cells showing typical neuronal morphologies and expressing multiple neuronal markers, even after downregulation of the exogenous transcription factors. Importantly, the vast majority of human iN cells were able to generate action potentials and many matured to receive synaptic contacts when co-cultured with primary mouse cortical neurons. Our data demonstrate that non-neural human somatic cells, as well as pluripotent stem cells, can be converted directly into neurons by lineage-determining transcription factors. These methods may facilitate robust generation of patient-specific human neurons for in vitro disease modelling or future applications in regenerative medicine.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159048/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159048/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pang, Zhiping P -- Yang, Nan -- Vierbuchen, Thomas -- Ostermeier, Austin -- Fuentes, Daniel R -- Yang, Troy Q -- Citri, Ami -- Sebastiano, Vittorio -- Marro, Samuele -- Sudhof, Thomas C -- Wernig, Marius -- 1R01MH092931/MH/NIMH NIH HHS/ -- R01 MH092931/MH/NIMH NIH HHS/ -- R01 MH092931-01/MH/NIMH NIH HHS/ -- RC4 NS073015/NS/NINDS NIH HHS/ -- RC4 NS073015-01/NS/NINDS NIH HHS/ -- RC4NS073015/NS/NINDS NIH HHS/ -- T32 CA009302/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 May 26;476(7359):220-3. doi: 10.1038/nature10202.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 265 Campus Drive, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21617644" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism
;
*Cell Differentiation
;
Cell Line
;
Cells, Cultured
;
*Cellular Reprogramming/genetics/physiology
;
Cerebral Cortex/cytology
;
Coculture Techniques
;
DNA-Binding Proteins/genetics/metabolism
;
Electric Conductivity
;
Fibroblasts/cytology/metabolism
;
Humans
;
Membrane Potentials
;
Mice
;
Nerve Tissue Proteins/genetics/metabolism
;
Neurons/*cytology/*metabolism
;
POU Domain Factors/genetics/metabolism
;
Pluripotent Stem Cells/cytology/metabolism
;
Regenerative Medicine
;
Synapses/metabolism
;
Transcription Factors/genetics/*metabolism
;
Transgenes
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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