In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state
Nuclear transplantation can reprogramme a somatic genome back into an embryonic epigenetic state, and the reprogrammed nucleus can create a cloned animal or produce pluripotent embryonic stem cells. One potential use of the nuclear cloning approach is the derivation of ‘customized’ embryonic stem (E...
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| Veröffentlicht in: | Nature 2007-07, Vol.448 (7151), p.318-324 |
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| creator | Jaenisch, Rudolf Wernig, Marius Meissner, Alexander Foreman, Ruth Brambrink, Tobias Ku, Manching Hochedlinger, Konrad Bernstein, Bradley E |
| description | Nuclear transplantation can reprogramme a somatic genome back into an embryonic epigenetic state, and the reprogrammed nucleus can create a cloned animal or produce pluripotent embryonic stem cells. One potential use of the nuclear cloning approach is the derivation of ‘customized’ embryonic stem (ES) cells for patient-specific cell treatment, but technical and ethical considerations impede the therapeutic application of this technology. Reprogramming of fibroblasts to a pluripotent state can be induced
in vitro
through ectopic expression of the four transcription factors Oct4 (also called Oct3/4 or Pou5f1), Sox2, c-Myc and Klf4. Here we show that DNA methylation, gene expression and chromatin state of such induced reprogrammed stem cells are similar to those of ES cells. Notably, the cells—derived from mouse fibroblasts—can form viable chimaeras, can contribute to the germ line and can generate live late-term embryos when injected into tetraploid blastocysts. Our results show that the biological potency and epigenetic state of
in-vitro
-reprogrammed induced pluripotent stem cells are indistinguishable from those of ES cells.
Stem cells with potential
The search for new ways of coaxing readily available cells to show the pluripotent activity of embryonic stem cells — the potential to differentiate into virtually any cell type — continues. The stakes are high, since if it can be achieved safely for human cells, cell transplantation therapy, even patient-specific therapy, will have come a step closer. Two groups now report an important advance in this direction: the creation of pluripotent stem cells from mouse fibroblasts. The epigenetic reprogramming requires the expression of four transcription factors, Oct3/4, Sox2, c-Myc and Klf4. The resulting cells resemble embryonic stem cells in both biological potency and epigenetic state.
Four transcription factors Oct4, Sox2, c-Myc and Klf4 are known to convert fibroblasts to pluripotent stem cells, if
Fbx
15 expression is also selected. But the induced stem cells were shown to be distinct from normal embryonic stem cells. However, if cells expressing
Nanog
and Oct4 are selected, then the reprogrammed fibroblasts are similar to embryonic stem cells in both biological potency and epigenetic state. |
| doi_str_mv | 10.1038/nature05944 |
| format | Article |
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in vitro
through ectopic expression of the four transcription factors Oct4 (also called Oct3/4 or Pou5f1), Sox2, c-Myc and Klf4. Here we show that DNA methylation, gene expression and chromatin state of such induced reprogrammed stem cells are similar to those of ES cells. Notably, the cells—derived from mouse fibroblasts—can form viable chimaeras, can contribute to the germ line and can generate live late-term embryos when injected into tetraploid blastocysts. Our results show that the biological potency and epigenetic state of
in-vitro
-reprogrammed induced pluripotent stem cells are indistinguishable from those of ES cells.
Stem cells with potential
The search for new ways of coaxing readily available cells to show the pluripotent activity of embryonic stem cells — the potential to differentiate into virtually any cell type — continues. The stakes are high, since if it can be achieved safely for human cells, cell transplantation therapy, even patient-specific therapy, will have come a step closer. Two groups now report an important advance in this direction: the creation of pluripotent stem cells from mouse fibroblasts. The epigenetic reprogramming requires the expression of four transcription factors, Oct3/4, Sox2, c-Myc and Klf4. The resulting cells resemble embryonic stem cells in both biological potency and epigenetic state.
Four transcription factors Oct4, Sox2, c-Myc and Klf4 are known to convert fibroblasts to pluripotent stem cells, if
Fbx
15 expression is also selected. But the induced stem cells were shown to be distinct from normal embryonic stem cells. However, if cells expressing
Nanog
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in vitro
through ectopic expression of the four transcription factors Oct4 (also called Oct3/4 or Pou5f1), Sox2, c-Myc and Klf4. Here we show that DNA methylation, gene expression and chromatin state of such induced reprogrammed stem cells are similar to those of ES cells. Notably, the cells—derived from mouse fibroblasts—can form viable chimaeras, can contribute to the germ line and can generate live late-term embryos when injected into tetraploid blastocysts. Our results show that the biological potency and epigenetic state of
in-vitro
-reprogrammed induced pluripotent stem cells are indistinguishable from those of ES cells.
Stem cells with potential
The search for new ways of coaxing readily available cells to show the pluripotent activity of embryonic stem cells — the potential to differentiate into virtually any cell type — continues. The stakes are high, since if it can be achieved safely for human cells, cell transplantation therapy, even patient-specific therapy, will have come a step closer. Two groups now report an important advance in this direction: the creation of pluripotent stem cells from mouse fibroblasts. The epigenetic reprogramming requires the expression of four transcription factors, Oct3/4, Sox2, c-Myc and Klf4. The resulting cells resemble embryonic stem cells in both biological potency and epigenetic state.
Four transcription factors Oct4, Sox2, c-Myc and Klf4 are known to convert fibroblasts to pluripotent stem cells, if
Fbx
15 expression is also selected. But the induced stem cells were shown to be distinct from normal embryonic stem cells. However, if cells expressing
Nanog
and Oct4 are selected, then the reprogrammed fibroblasts are similar to embryonic stem cells in both biological potency and epigenetic state.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Differentiation</subject><subject>Cell Lineage</subject><subject>Chimera - embryology</subject><subject>Chimera - genetics</subject><subject>Chimera - growth & development</subject><subject>Chimera - metabolism</subject><subject>Chromatin - genetics</subject><subject>Chromatin - metabolism</subject><subject>Cloning</subject><subject>Deoxyribonucleic acid</subject><subject>Derivation</subject><subject>DNA</subject><subject>DNA binding proteins</subject><subject>DNA Methylation</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Embryology: invertebrates and vertebrates. 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Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><jtitle>Nature</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jaenisch, Rudolf</au><au>Wernig, Marius</au><au>Meissner, Alexander</au><au>Foreman, Ruth</au><au>Brambrink, Tobias</au><au>Ku, Manching</au><au>Hochedlinger, Konrad</au><au>Bernstein, Bradley E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state</atitle><jtitle>Nature</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>2007-07-19</date><risdate>2007</risdate><volume>448</volume><issue>7151</issue><spage>318</spage><epage>324</epage><pages>318-324</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><eissn>1476-4679</eissn><coden>NATUAS</coden><abstract>Nuclear transplantation can reprogramme a somatic genome back into an embryonic epigenetic state, and the reprogrammed nucleus can create a cloned animal or produce pluripotent embryonic stem cells. One potential use of the nuclear cloning approach is the derivation of ‘customized’ embryonic stem (ES) cells for patient-specific cell treatment, but technical and ethical considerations impede the therapeutic application of this technology. Reprogramming of fibroblasts to a pluripotent state can be induced
in vitro
through ectopic expression of the four transcription factors Oct4 (also called Oct3/4 or Pou5f1), Sox2, c-Myc and Klf4. Here we show that DNA methylation, gene expression and chromatin state of such induced reprogrammed stem cells are similar to those of ES cells. Notably, the cells—derived from mouse fibroblasts—can form viable chimaeras, can contribute to the germ line and can generate live late-term embryos when injected into tetraploid blastocysts. Our results show that the biological potency and epigenetic state of
in-vitro
-reprogrammed induced pluripotent stem cells are indistinguishable from those of ES cells.
Stem cells with potential
The search for new ways of coaxing readily available cells to show the pluripotent activity of embryonic stem cells — the potential to differentiate into virtually any cell type — continues. The stakes are high, since if it can be achieved safely for human cells, cell transplantation therapy, even patient-specific therapy, will have come a step closer. Two groups now report an important advance in this direction: the creation of pluripotent stem cells from mouse fibroblasts. The epigenetic reprogramming requires the expression of four transcription factors, Oct3/4, Sox2, c-Myc and Klf4. The resulting cells resemble embryonic stem cells in both biological potency and epigenetic state.
Four transcription factors Oct4, Sox2, c-Myc and Klf4 are known to convert fibroblasts to pluripotent stem cells, if
Fbx
15 expression is also selected. But the induced stem cells were shown to be distinct from normal embryonic stem cells. However, if cells expressing
Nanog
and Oct4 are selected, then the reprogrammed fibroblasts are similar to embryonic stem cells in both biological potency and epigenetic state.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>17554336</pmid><doi>10.1038/nature05944</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature, 2007-07, Vol.448 (7151), p.318-324 |
| issn | 0028-0836 1476-4687 1476-4679 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_743355799 |
| source | MEDLINE; Nature; SpringerLink Journals - AutoHoldings |
| subjects | Animals Biological and medical sciences Cell Differentiation Cell Lineage Chimera - embryology Chimera - genetics Chimera - growth & development Chimera - metabolism Chromatin - genetics Chromatin - metabolism Cloning Deoxyribonucleic acid Derivation DNA DNA binding proteins DNA Methylation DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Embryology: invertebrates and vertebrates. Teratology Embryos Ethics Evaluation Female Fibroblasts Fibroblasts - cytology Fibroblasts - metabolism Fundamental and applied biological sciences. Psychology Gene expression Gene Silencing Genomes Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humanities and Social Sciences In vitro testing Male Methylation Mice Molecular embryology multidisciplinary Nanog Homeobox Protein Nucleotide sequence Octamer Transcription Factor-3 - genetics Octamer Transcription Factor-3 - metabolism Pluripotent Stem Cells - cytology Pluripotent Stem Cells - metabolism Rodents Science Science (multidisciplinary) Stem cell research Stem cells Teratoma - metabolism Teratoma - pathology |
| title | In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state |
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