An integrated systems biology approach identifies positive cofactor 4 as a factor that increases reprogramming efficiency
Spermatogonial stem cells (SSCs) can spontaneously dedifferentiate into embryonic stem cell (ESC)-like cells, which are designated as multipotent SSCs (mSSCs), without ectopic expression of reprogramming factors. Interestingly, SSCs express key pluripotency genes such as Oct4, Sox2, Klf4 and Myc. Th...
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| Veröffentlicht in: | Nucleic acids research 2016-02, Vol.44 (3), p.1203-1215 |
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| container_title | Nucleic acids research |
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| creator | Jo, Junghyun Hwang, Sohyun Kim, Hyung Joon Hong, Soomin Lee, Jeoung Eun Lee, Sung-Geum Baek, Ahmi Han, Heonjong Lee, Jin Il Lee, Insuk Lee, Dong Ryul |
| description | Spermatogonial stem cells (SSCs) can spontaneously dedifferentiate into embryonic stem cell (ESC)-like cells, which are designated as multipotent SSCs (mSSCs), without ectopic expression of reprogramming factors. Interestingly, SSCs express key pluripotency genes such as Oct4, Sox2, Klf4 and Myc. Therefore, molecular dissection of mSSC reprogramming may provide clues about novel endogenous reprogramming or pluripotency regulatory factors. Our comparative transcriptome analysis of mSSCs and induced pluripotent stem cells (iPSCs) suggests that they have similar pluripotency states but are reprogrammed via different transcriptional pathways. We identified 53 genes as putative pluripotency regulatory factors using an integrated systems biology approach. We demonstrated a selected candidate, Positive cofactor 4 (Pc4), can enhance the efficiency of somatic cell reprogramming by promoting and maintaining transcriptional activity of the key reprograming factors. These results suggest that Pc4 has an important role in inducing spontaneous somatic cell reprogramming via up-regulation of key pluripotency genes. |
| doi_str_mv | 10.1093/nar/gkv1468 |
| format | Article |
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Interestingly, SSCs express key pluripotency genes such as Oct4, Sox2, Klf4 and Myc. Therefore, molecular dissection of mSSC reprogramming may provide clues about novel endogenous reprogramming or pluripotency regulatory factors. Our comparative transcriptome analysis of mSSCs and induced pluripotent stem cells (iPSCs) suggests that they have similar pluripotency states but are reprogrammed via different transcriptional pathways. We identified 53 genes as putative pluripotency regulatory factors using an integrated systems biology approach. We demonstrated a selected candidate, Positive cofactor 4 (Pc4), can enhance the efficiency of somatic cell reprogramming by promoting and maintaining transcriptional activity of the key reprograming factors. These results suggest that Pc4 has an important role in inducing spontaneous somatic cell reprogramming via up-regulation of key pluripotency genes.</description><identifier>ISSN: 0305-1048</identifier><identifier>EISSN: 1362-4962</identifier><identifier>DOI: 10.1093/nar/gkv1468</identifier><identifier>PMID: 26740582</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adult Stem Cells - cytology ; Adult Stem Cells - metabolism ; Animals ; Blotting, Western ; Cells, Cultured ; Cellular Reprogramming - genetics ; Cluster Analysis ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Gene Expression Profiling ; Induced Pluripotent Stem Cells - cytology ; Induced Pluripotent Stem Cells - metabolism ; Kruppel-Like Transcription Factors - genetics ; Kruppel-Like Transcription Factors - metabolism ; Mice ; Mice, Inbred C57BL ; Molecular Biology ; Mouse Embryonic Stem Cells - cytology ; Mouse Embryonic Stem Cells - metabolism ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Octamer Transcription Factor-3 - genetics ; Octamer Transcription Factor-3 - metabolism ; Oligonucleotide Array Sequence Analysis ; Proto-Oncogene Proteins c-myc - genetics ; Proto-Oncogene Proteins c-myc - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; SOXB1 Transcription Factors - genetics ; SOXB1 Transcription Factors - metabolism ; Systems Biology - methods ; Transcription Factors - genetics ; Transcription Factors - metabolism</subject><ispartof>Nucleic acids research, 2016-02, Vol.44 (3), p.1203-1215</ispartof><rights>The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.</rights><rights>The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-97ed0821b0b903ec69b840ddc8f09af71b989dce7c671b5896592cdfde3c0f8e3</citedby><cites>FETCH-LOGICAL-c381t-97ed0821b0b903ec69b840ddc8f09af71b989dce7c671b5896592cdfde3c0f8e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756831/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756831/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26740582$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jo, Junghyun</creatorcontrib><creatorcontrib>Hwang, Sohyun</creatorcontrib><creatorcontrib>Kim, Hyung Joon</creatorcontrib><creatorcontrib>Hong, Soomin</creatorcontrib><creatorcontrib>Lee, Jeoung Eun</creatorcontrib><creatorcontrib>Lee, Sung-Geum</creatorcontrib><creatorcontrib>Baek, Ahmi</creatorcontrib><creatorcontrib>Han, Heonjong</creatorcontrib><creatorcontrib>Lee, Jin Il</creatorcontrib><creatorcontrib>Lee, Insuk</creatorcontrib><creatorcontrib>Lee, Dong Ryul</creatorcontrib><title>An integrated systems biology approach identifies positive cofactor 4 as a factor that increases reprogramming efficiency</title><title>Nucleic acids research</title><addtitle>Nucleic Acids Res</addtitle><description>Spermatogonial stem cells (SSCs) can spontaneously dedifferentiate into embryonic stem cell (ESC)-like cells, which are designated as multipotent SSCs (mSSCs), without ectopic expression of reprogramming factors. 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These results suggest that Pc4 has an important role in inducing spontaneous somatic cell reprogramming via up-regulation of key pluripotency genes.</description><subject>Adult Stem Cells - cytology</subject><subject>Adult Stem Cells - metabolism</subject><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cells, Cultured</subject><subject>Cellular Reprogramming - genetics</subject><subject>Cluster Analysis</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Gene Expression Profiling</subject><subject>Induced Pluripotent Stem Cells - cytology</subject><subject>Induced Pluripotent Stem Cells - metabolism</subject><subject>Kruppel-Like Transcription Factors - genetics</subject><subject>Kruppel-Like Transcription Factors - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Molecular Biology</subject><subject>Mouse Embryonic Stem Cells - cytology</subject><subject>Mouse Embryonic Stem Cells - metabolism</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Octamer Transcription Factor-3 - genetics</subject><subject>Octamer Transcription Factor-3 - metabolism</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Proto-Oncogene Proteins c-myc - genetics</subject><subject>Proto-Oncogene Proteins c-myc - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>SOXB1 Transcription Factors - genetics</subject><subject>SOXB1 Transcription Factors - metabolism</subject><subject>Systems Biology - methods</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkcFrFTEQh0OxtK_Vk3fJUZC1ySabTS5CKdUKhV70HLLZyb7obrImeQ_2vzfSZ9HTzDAf3wz8EHpLyUdKFLsJJt1MP4-UC3mGdpSJtuFKtK_QjjDSNZRweYmucv5BCOW04xfoshU9J51sd2i7DdiHAlMyBUact1xgyXjwcY7Ths26pmjsHvsRQvHOQ8ZrzL74I2AbnbElJsyxydjg01T2plSnTWByxRNURdUviw8TBue89RDs9hqdOzNneHOq1-j75_tvdw_N49OXr3e3j41lkpZG9TAS2dKBDIowsEINkpNxtNIRZVxPByXVaKG3ovadVKJTrR3dCMwSJ4Fdo0_P3vUwLFDJUJKZ9Zr8YtKmo_H6_03wez3Fo-Z9JySjVfD-JEjx1wFy0YvPFubZBIiHrGkveiKEkn1FPzyjNsWcE7iXM5ToP2HpGpY-hVXpd_9-9sL-TYf9BhHqlcg</recordid><startdate>20160218</startdate><enddate>20160218</enddate><creator>Jo, Junghyun</creator><creator>Hwang, Sohyun</creator><creator>Kim, Hyung Joon</creator><creator>Hong, Soomin</creator><creator>Lee, Jeoung Eun</creator><creator>Lee, Sung-Geum</creator><creator>Baek, Ahmi</creator><creator>Han, Heonjong</creator><creator>Lee, Jin Il</creator><creator>Lee, Insuk</creator><creator>Lee, Dong Ryul</creator><general>Oxford University Press</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160218</creationdate><title>An integrated systems biology approach identifies positive cofactor 4 as a factor that increases reprogramming efficiency</title><author>Jo, Junghyun ; Hwang, Sohyun ; Kim, Hyung Joon ; Hong, Soomin ; Lee, Jeoung Eun ; Lee, Sung-Geum ; Baek, Ahmi ; Han, Heonjong ; Lee, Jin Il ; Lee, Insuk ; Lee, Dong Ryul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-97ed0821b0b903ec69b840ddc8f09af71b989dce7c671b5896592cdfde3c0f8e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult Stem Cells - cytology</topic><topic>Adult Stem Cells - metabolism</topic><topic>Animals</topic><topic>Blotting, Western</topic><topic>Cells, Cultured</topic><topic>Cellular Reprogramming - genetics</topic><topic>Cluster Analysis</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Gene Expression Profiling</topic><topic>Induced Pluripotent Stem Cells - cytology</topic><topic>Induced Pluripotent Stem Cells - metabolism</topic><topic>Kruppel-Like Transcription Factors - genetics</topic><topic>Kruppel-Like Transcription Factors - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Molecular Biology</topic><topic>Mouse Embryonic Stem Cells - cytology</topic><topic>Mouse Embryonic Stem Cells - metabolism</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Octamer Transcription Factor-3 - genetics</topic><topic>Octamer Transcription Factor-3 - metabolism</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Proto-Oncogene Proteins c-myc - genetics</topic><topic>Proto-Oncogene Proteins c-myc - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>SOXB1 Transcription Factors - genetics</topic><topic>SOXB1 Transcription Factors - metabolism</topic><topic>Systems Biology - methods</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jo, Junghyun</creatorcontrib><creatorcontrib>Hwang, Sohyun</creatorcontrib><creatorcontrib>Kim, Hyung Joon</creatorcontrib><creatorcontrib>Hong, Soomin</creatorcontrib><creatorcontrib>Lee, Jeoung Eun</creatorcontrib><creatorcontrib>Lee, Sung-Geum</creatorcontrib><creatorcontrib>Baek, Ahmi</creatorcontrib><creatorcontrib>Han, Heonjong</creatorcontrib><creatorcontrib>Lee, Jin Il</creatorcontrib><creatorcontrib>Lee, Insuk</creatorcontrib><creatorcontrib>Lee, Dong Ryul</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jo, Junghyun</au><au>Hwang, Sohyun</au><au>Kim, Hyung Joon</au><au>Hong, Soomin</au><au>Lee, Jeoung Eun</au><au>Lee, Sung-Geum</au><au>Baek, Ahmi</au><au>Han, Heonjong</au><au>Lee, Jin Il</au><au>Lee, Insuk</au><au>Lee, Dong Ryul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An integrated systems biology approach identifies positive cofactor 4 as a factor that increases reprogramming efficiency</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2016-02-18</date><risdate>2016</risdate><volume>44</volume><issue>3</issue><spage>1203</spage><epage>1215</epage><pages>1203-1215</pages><issn>0305-1048</issn><eissn>1362-4962</eissn><abstract>Spermatogonial stem cells (SSCs) can spontaneously dedifferentiate into embryonic stem cell (ESC)-like cells, which are designated as multipotent SSCs (mSSCs), without ectopic expression of reprogramming factors. Interestingly, SSCs express key pluripotency genes such as Oct4, Sox2, Klf4 and Myc. Therefore, molecular dissection of mSSC reprogramming may provide clues about novel endogenous reprogramming or pluripotency regulatory factors. Our comparative transcriptome analysis of mSSCs and induced pluripotent stem cells (iPSCs) suggests that they have similar pluripotency states but are reprogrammed via different transcriptional pathways. We identified 53 genes as putative pluripotency regulatory factors using an integrated systems biology approach. We demonstrated a selected candidate, Positive cofactor 4 (Pc4), can enhance the efficiency of somatic cell reprogramming by promoting and maintaining transcriptional activity of the key reprograming factors. These results suggest that Pc4 has an important role in inducing spontaneous somatic cell reprogramming via up-regulation of key pluripotency genes.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>26740582</pmid><doi>10.1093/nar/gkv1468</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Stem Cells - cytology Adult Stem Cells - metabolism Animals Blotting, Western Cells, Cultured Cellular Reprogramming - genetics Cluster Analysis DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Gene Expression Profiling Induced Pluripotent Stem Cells - cytology Induced Pluripotent Stem Cells - metabolism Kruppel-Like Transcription Factors - genetics Kruppel-Like Transcription Factors - metabolism Mice Mice, Inbred C57BL Molecular Biology Mouse Embryonic Stem Cells - cytology Mouse Embryonic Stem Cells - metabolism Nuclear Proteins - genetics Nuclear Proteins - metabolism Octamer Transcription Factor-3 - genetics Octamer Transcription Factor-3 - metabolism Oligonucleotide Array Sequence Analysis Proto-Oncogene Proteins c-myc - genetics Proto-Oncogene Proteins c-myc - metabolism Reverse Transcriptase Polymerase Chain Reaction SOXB1 Transcription Factors - genetics SOXB1 Transcription Factors - metabolism Systems Biology - methods Transcription Factors - genetics Transcription Factors - metabolism |
| title | An integrated systems biology approach identifies positive cofactor 4 as a factor that increases reprogramming efficiency |
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