Direct generation of human naive induced pluripotent stem cells from somatic cells in microfluidics
Induced pluripotent stem cells (iPSCs) are generated via the expression of the transcription factors OCT4 (also known as POU5F1 ), SOX2 , KLF4 and cMYC (OSKM) in somatic cells. In contrast to murine naive iPSCs, conventional human iPSCs are in a more developmentally advanced state called primed plur...
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| Veröffentlicht in: | Nature cell biology 2019-02, Vol.21 (2), p.275-286 |
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| creator | Giulitti, Stefano Pellegrini, Marco Zorzan, Irene Martini, Paolo Gagliano, Onelia Mutarelli, Margherita Ziller, Michael Johannes Cacchiarelli, Davide Romualdi, Chiara Elvassore, Nicola Martello, Graziano |
| description | Induced pluripotent stem cells (iPSCs) are generated via the expression of the transcription factors
OCT4
(also known as
POU5F1
),
SOX2
,
KLF4
and
cMYC
(OSKM) in somatic cells. In contrast to murine naive iPSCs, conventional human iPSCs are in a more developmentally advanced state called primed pluripotency. Here, we report that human naive iPSCs (niPSCs) can be generated directly from fewer than 1,000 primary human somatic cells, without requiring stable genetic manipulation, via the delivery of modified messenger RNAs using microfluidics. Expression of the OSKM factors in combination with
NANOG
for 12 days generates niPSCs that are free of transgenes, karyotypically normal and display transcriptional, epigenetic and metabolic features indicative of the naive state. Importantly, niPSCs efficiently differentiate into all three germ layers. While niPSCs can be generated at low frequency under conventional conditions, our microfluidics approach enables the robust and cost-effective production of patient-specific niPSCs for regenerative medicine applications, including disease modelling and drug screening.
Giulitti et al. deliver modified mRNAs encoding OCT3/4, SOX2, KLF4 and cMYC as well as NANOG in microfluidics to directly convert human fibroblasts into naive induced pluripotent stem cells; the confined environment leads to enhanced efficiency and homogeneity compared to traditional methods. |
| doi_str_mv | 10.1038/s41556-018-0254-5 |
| format | Article |
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OCT4
(also known as
POU5F1
),
SOX2
,
KLF4
and
cMYC
(OSKM) in somatic cells. In contrast to murine naive iPSCs, conventional human iPSCs are in a more developmentally advanced state called primed pluripotency. Here, we report that human naive iPSCs (niPSCs) can be generated directly from fewer than 1,000 primary human somatic cells, without requiring stable genetic manipulation, via the delivery of modified messenger RNAs using microfluidics. Expression of the OSKM factors in combination with
NANOG
for 12 days generates niPSCs that are free of transgenes, karyotypically normal and display transcriptional, epigenetic and metabolic features indicative of the naive state. Importantly, niPSCs efficiently differentiate into all three germ layers. While niPSCs can be generated at low frequency under conventional conditions, our microfluidics approach enables the robust and cost-effective production of patient-specific niPSCs for regenerative medicine applications, including disease modelling and drug screening.
Giulitti et al. deliver modified mRNAs encoding OCT3/4, SOX2, KLF4 and cMYC as well as NANOG in microfluidics to directly convert human fibroblasts into naive induced pluripotent stem cells; the confined environment leads to enhanced efficiency and homogeneity compared to traditional methods.</description><identifier>ISSN: 1465-7392</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/s41556-018-0254-5</identifier><identifier>PMID: 30598530</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/1 ; 13/100 ; 13/106 ; 13/109 ; 13/21 ; 13/31 ; 13/51 ; 13/62 ; 14/19 ; 38/77 ; 38/91 ; 45/23 ; 631/136/2444 ; 631/532 ; 631/532/2435 ; 96 ; Animals ; Biomedical and Life Sciences ; Cancer Research ; Cell Biology ; Cell Differentiation ; Cells, Cultured ; Developmental Biology ; Displays (Marketing) ; DNA binding proteins ; Drug evaluation ; Drug screening ; Epigenetic inheritance ; Genetic aspects ; Genetic engineering ; Germ Layers - cytology ; Germ Layers - metabolism ; Health screening ; Human genetic engineering ; Humans ; Induced Pluripotent Stem Cells - cytology ; Induced Pluripotent Stem Cells - metabolism ; Karyotype ; KLF4 protein ; Kruppel-Like Transcription Factors - genetics ; Life Sciences ; Mammals ; Messenger RNA ; Methods ; Mice ; Microfluidics ; Microfluidics - methods ; Oct-4 protein ; Octamer Transcription Factor-3 - genetics ; Pluripotency ; Proto-Oncogene Proteins c-myc - genetics ; Regenerative medicine ; Regenerative Medicine - methods ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Somatic cells ; SOXB1 Transcription Factors - genetics ; Stem cell transplantation ; Stem Cells ; technical-report ; Tissue engineering ; Transcription factors ; Transgenes</subject><ispartof>Nature cell biology, 2019-02, Vol.21 (2), p.275-286</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2018</rights><rights>COPYRIGHT 2019 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Feb 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-f02ba83fd9405f8a00ebb9cecd447514ad24efd4688160fc2fb845de50daaa5c3</citedby><cites>FETCH-LOGICAL-c473t-f02ba83fd9405f8a00ebb9cecd447514ad24efd4688160fc2fb845de50daaa5c3</cites><orcidid>0000-0002-7749-653X ; 0000-0001-5520-085X ; 0000-0002-7029-6287 ; 0000-0002-3724-6640</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41556-018-0254-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41556-018-0254-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30598530$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Giulitti, Stefano</creatorcontrib><creatorcontrib>Pellegrini, Marco</creatorcontrib><creatorcontrib>Zorzan, Irene</creatorcontrib><creatorcontrib>Martini, Paolo</creatorcontrib><creatorcontrib>Gagliano, Onelia</creatorcontrib><creatorcontrib>Mutarelli, Margherita</creatorcontrib><creatorcontrib>Ziller, Michael Johannes</creatorcontrib><creatorcontrib>Cacchiarelli, Davide</creatorcontrib><creatorcontrib>Romualdi, Chiara</creatorcontrib><creatorcontrib>Elvassore, Nicola</creatorcontrib><creatorcontrib>Martello, Graziano</creatorcontrib><title>Direct generation of human naive induced pluripotent stem cells from somatic cells in microfluidics</title><title>Nature cell biology</title><addtitle>Nat Cell Biol</addtitle><addtitle>Nat Cell Biol</addtitle><description>Induced pluripotent stem cells (iPSCs) are generated via the expression of the transcription factors
OCT4
(also known as
POU5F1
),
SOX2
,
KLF4
and
cMYC
(OSKM) in somatic cells. In contrast to murine naive iPSCs, conventional human iPSCs are in a more developmentally advanced state called primed pluripotency. Here, we report that human naive iPSCs (niPSCs) can be generated directly from fewer than 1,000 primary human somatic cells, without requiring stable genetic manipulation, via the delivery of modified messenger RNAs using microfluidics. Expression of the OSKM factors in combination with
NANOG
for 12 days generates niPSCs that are free of transgenes, karyotypically normal and display transcriptional, epigenetic and metabolic features indicative of the naive state. Importantly, niPSCs efficiently differentiate into all three germ layers. While niPSCs can be generated at low frequency under conventional conditions, our microfluidics approach enables the robust and cost-effective production of patient-specific niPSCs for regenerative medicine applications, including disease modelling and drug screening.
Giulitti et al. deliver modified mRNAs encoding OCT3/4, SOX2, KLF4 and cMYC as well as NANOG in microfluidics to directly convert human fibroblasts into naive induced pluripotent stem cells; the confined environment leads to enhanced efficiency and homogeneity compared to traditional methods.</description><subject>13/1</subject><subject>13/100</subject><subject>13/106</subject><subject>13/109</subject><subject>13/21</subject><subject>13/31</subject><subject>13/51</subject><subject>13/62</subject><subject>14/19</subject><subject>38/77</subject><subject>38/91</subject><subject>45/23</subject><subject>631/136/2444</subject><subject>631/532</subject><subject>631/532/2435</subject><subject>96</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Cancer Research</subject><subject>Cell Biology</subject><subject>Cell Differentiation</subject><subject>Cells, Cultured</subject><subject>Developmental Biology</subject><subject>Displays (Marketing)</subject><subject>DNA binding proteins</subject><subject>Drug evaluation</subject><subject>Drug screening</subject><subject>Epigenetic inheritance</subject><subject>Genetic aspects</subject><subject>Genetic engineering</subject><subject>Germ Layers - cytology</subject><subject>Germ Layers - metabolism</subject><subject>Health screening</subject><subject>Human genetic engineering</subject><subject>Humans</subject><subject>Induced Pluripotent Stem Cells - cytology</subject><subject>Induced Pluripotent Stem Cells - metabolism</subject><subject>Karyotype</subject><subject>KLF4 protein</subject><subject>Kruppel-Like Transcription Factors - genetics</subject><subject>Life Sciences</subject><subject>Mammals</subject><subject>Messenger RNA</subject><subject>Methods</subject><subject>Mice</subject><subject>Microfluidics</subject><subject>Microfluidics - methods</subject><subject>Oct-4 protein</subject><subject>Octamer Transcription Factor-3 - genetics</subject><subject>Pluripotency</subject><subject>Proto-Oncogene Proteins c-myc - genetics</subject><subject>Regenerative medicine</subject><subject>Regenerative Medicine - methods</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Somatic cells</subject><subject>SOXB1 Transcription Factors - genetics</subject><subject>Stem cell transplantation</subject><subject>Stem Cells</subject><subject>technical-report</subject><subject>Tissue engineering</subject><subject>Transcription factors</subject><subject>Transgenes</subject><issn>1465-7392</issn><issn>1476-4679</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kk1v1DAQhiMEoqXwA7ggS1zgkDJ27MQ5VqWFSpWQ-DhbXnu8uErsxXYQ_Hsc7UK1COSDrZnnHc2M36Z5TuGcQiffZE6F6FugsgUmeCseNKeUD33L-2F8uL570Q7dyE6aJznfAVDOYXjcnHQgRik6OG3MW5_QFLLFgEkXHwOJjnxdZh1I0P47Eh_sYtCS3bQkv4sFQyG54EwMTlMmLsWZ5DhXrTmEfCCzNym6afHWm_y0eeT0lPHZ4T5rvlxffb58395-eHdzeXHbGj50pXXANlp2zo4chJMaADeb0aCxnA-Ccm0ZR2d5LyXtwRnmNpILiwKs1lqY7qx5ta-7S_Hbgrmo2ee1JR0wLlkx2jM-SmCyoi__Qu_ikkLtrlIDHzjn43hPbfWEygcXS9JmLaouxMB66Bis1Pk_qHos1jXEgM7X-JHg9ZGgMgV_lK1eclY3nz4es3TP1n3mnNCpXfKzTj8VBbWaQO1NoKoJ1GoCJarmxWG4ZTOj_aP4_esVYHsg11TYYrqf_v9VfwG0mrtd</recordid><startdate>20190201</startdate><enddate>20190201</enddate><creator>Giulitti, Stefano</creator><creator>Pellegrini, Marco</creator><creator>Zorzan, Irene</creator><creator>Martini, Paolo</creator><creator>Gagliano, Onelia</creator><creator>Mutarelli, Margherita</creator><creator>Ziller, Michael Johannes</creator><creator>Cacchiarelli, Davide</creator><creator>Romualdi, Chiara</creator><creator>Elvassore, Nicola</creator><creator>Martello, Graziano</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7749-653X</orcidid><orcidid>https://orcid.org/0000-0001-5520-085X</orcidid><orcidid>https://orcid.org/0000-0002-7029-6287</orcidid><orcidid>https://orcid.org/0000-0002-3724-6640</orcidid></search><sort><creationdate>20190201</creationdate><title>Direct generation of human naive induced pluripotent stem cells from somatic cells in microfluidics</title><author>Giulitti, Stefano ; Pellegrini, Marco ; Zorzan, Irene ; Martini, Paolo ; Gagliano, Onelia ; Mutarelli, Margherita ; Ziller, Michael Johannes ; Cacchiarelli, Davide ; Romualdi, Chiara ; Elvassore, Nicola ; Martello, Graziano</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c473t-f02ba83fd9405f8a00ebb9cecd447514ad24efd4688160fc2fb845de50daaa5c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>13/1</topic><topic>13/100</topic><topic>13/106</topic><topic>13/109</topic><topic>13/21</topic><topic>13/31</topic><topic>13/51</topic><topic>13/62</topic><topic>14/19</topic><topic>38/77</topic><topic>38/91</topic><topic>45/23</topic><topic>631/136/2444</topic><topic>631/532</topic><topic>631/532/2435</topic><topic>96</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Cancer Research</topic><topic>Cell Biology</topic><topic>Cell Differentiation</topic><topic>Cells, Cultured</topic><topic>Developmental Biology</topic><topic>Displays (Marketing)</topic><topic>DNA binding proteins</topic><topic>Drug evaluation</topic><topic>Drug screening</topic><topic>Epigenetic inheritance</topic><topic>Genetic aspects</topic><topic>Genetic engineering</topic><topic>Germ Layers - cytology</topic><topic>Germ Layers - metabolism</topic><topic>Health screening</topic><topic>Human genetic engineering</topic><topic>Humans</topic><topic>Induced Pluripotent Stem Cells - cytology</topic><topic>Induced Pluripotent Stem Cells - metabolism</topic><topic>Karyotype</topic><topic>KLF4 protein</topic><topic>Kruppel-Like Transcription Factors - genetics</topic><topic>Life Sciences</topic><topic>Mammals</topic><topic>Messenger RNA</topic><topic>Methods</topic><topic>Mice</topic><topic>Microfluidics</topic><topic>Microfluidics - methods</topic><topic>Oct-4 protein</topic><topic>Octamer Transcription Factor-3 - genetics</topic><topic>Pluripotency</topic><topic>Proto-Oncogene Proteins c-myc - genetics</topic><topic>Regenerative medicine</topic><topic>Regenerative Medicine - methods</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Somatic cells</topic><topic>SOXB1 Transcription Factors - genetics</topic><topic>Stem cell transplantation</topic><topic>Stem Cells</topic><topic>technical-report</topic><topic>Tissue engineering</topic><topic>Transcription factors</topic><topic>Transgenes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Giulitti, Stefano</creatorcontrib><creatorcontrib>Pellegrini, Marco</creatorcontrib><creatorcontrib>Zorzan, Irene</creatorcontrib><creatorcontrib>Martini, Paolo</creatorcontrib><creatorcontrib>Gagliano, Onelia</creatorcontrib><creatorcontrib>Mutarelli, Margherita</creatorcontrib><creatorcontrib>Ziller, Michael Johannes</creatorcontrib><creatorcontrib>Cacchiarelli, Davide</creatorcontrib><creatorcontrib>Romualdi, Chiara</creatorcontrib><creatorcontrib>Elvassore, Nicola</creatorcontrib><creatorcontrib>Martello, Graziano</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Giulitti, Stefano</au><au>Pellegrini, Marco</au><au>Zorzan, Irene</au><au>Martini, Paolo</au><au>Gagliano, Onelia</au><au>Mutarelli, Margherita</au><au>Ziller, Michael Johannes</au><au>Cacchiarelli, Davide</au><au>Romualdi, Chiara</au><au>Elvassore, Nicola</au><au>Martello, Graziano</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Direct generation of human naive induced pluripotent stem cells from somatic cells in microfluidics</atitle><jtitle>Nature cell biology</jtitle><stitle>Nat Cell Biol</stitle><addtitle>Nat Cell Biol</addtitle><date>2019-02-01</date><risdate>2019</risdate><volume>21</volume><issue>2</issue><spage>275</spage><epage>286</epage><pages>275-286</pages><issn>1465-7392</issn><eissn>1476-4679</eissn><abstract>Induced pluripotent stem cells (iPSCs) are generated via the expression of the transcription factors
OCT4
(also known as
POU5F1
),
SOX2
,
KLF4
and
cMYC
(OSKM) in somatic cells. In contrast to murine naive iPSCs, conventional human iPSCs are in a more developmentally advanced state called primed pluripotency. Here, we report that human naive iPSCs (niPSCs) can be generated directly from fewer than 1,000 primary human somatic cells, without requiring stable genetic manipulation, via the delivery of modified messenger RNAs using microfluidics. Expression of the OSKM factors in combination with
NANOG
for 12 days generates niPSCs that are free of transgenes, karyotypically normal and display transcriptional, epigenetic and metabolic features indicative of the naive state. Importantly, niPSCs efficiently differentiate into all three germ layers. While niPSCs can be generated at low frequency under conventional conditions, our microfluidics approach enables the robust and cost-effective production of patient-specific niPSCs for regenerative medicine applications, including disease modelling and drug screening.
Giulitti et al. deliver modified mRNAs encoding OCT3/4, SOX2, KLF4 and cMYC as well as NANOG in microfluidics to directly convert human fibroblasts into naive induced pluripotent stem cells; the confined environment leads to enhanced efficiency and homogeneity compared to traditional methods.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30598530</pmid><doi>10.1038/s41556-018-0254-5</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-7749-653X</orcidid><orcidid>https://orcid.org/0000-0001-5520-085X</orcidid><orcidid>https://orcid.org/0000-0002-7029-6287</orcidid><orcidid>https://orcid.org/0000-0002-3724-6640</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1465-7392 |
| ispartof | Nature cell biology, 2019-02, Vol.21 (2), p.275-286 |
| issn | 1465-7392 1476-4679 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2162498028 |
| source | MEDLINE; Nature; Springer Nature - Complete Springer Journals |
| subjects | 13/1 13/100 13/106 13/109 13/21 13/31 13/51 13/62 14/19 38/77 38/91 45/23 631/136/2444 631/532 631/532/2435 96 Animals Biomedical and Life Sciences Cancer Research Cell Biology Cell Differentiation Cells, Cultured Developmental Biology Displays (Marketing) DNA binding proteins Drug evaluation Drug screening Epigenetic inheritance Genetic aspects Genetic engineering Germ Layers - cytology Germ Layers - metabolism Health screening Human genetic engineering Humans Induced Pluripotent Stem Cells - cytology Induced Pluripotent Stem Cells - metabolism Karyotype KLF4 protein Kruppel-Like Transcription Factors - genetics Life Sciences Mammals Messenger RNA Methods Mice Microfluidics Microfluidics - methods Oct-4 protein Octamer Transcription Factor-3 - genetics Pluripotency Proto-Oncogene Proteins c-myc - genetics Regenerative medicine Regenerative Medicine - methods RNA, Messenger - genetics RNA, Messenger - metabolism Somatic cells SOXB1 Transcription Factors - genetics Stem cell transplantation Stem Cells technical-report Tissue engineering Transcription factors Transgenes |
| title | Direct generation of human naive induced pluripotent stem cells from somatic cells in microfluidics |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T21%3A17%3A19IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Direct%20generation%20of%20human%20naive%20induced%20pluripotent%20stem%20cells%20from%20somatic%20cells%20in%20microfluidics&rft.jtitle=Nature%20cell%20biology&rft.au=Giulitti,%20Stefano&rft.date=2019-02-01&rft.volume=21&rft.issue=2&rft.spage=275&rft.epage=286&rft.pages=275-286&rft.issn=1465-7392&rft.eissn=1476-4679&rft_id=info:doi/10.1038/s41556-018-0254-5&rft_dat=%3Cgale_proqu%3EA572603209%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2174744499&rft_id=info:pmid/30598530&rft_galeid=A572603209&rfr_iscdi=true |