Efficient differentiation of steroidogenic and germ-like cells from epigenetically-related iPSCs derived from ovarian granulosa cells
To explore restoration of ovarian function using epigenetically-related, induced pluripotent stem cells (iPSCs), we functionally evaluated the epigenetic memory of novel iPSC lines, derived from mouse and human ovarian granulosa cells (GCs) using c-Myc, Klf4, Sox2 and Oct4 retroviral vectors. The st...
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| Veröffentlicht in: | PloS one 2015-03, Vol.10 (3), p.e0119275 |
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| creator | Anchan, Raymond Gerami-Naini, Behzad Lindsey, Jennifer S Ho, Joshua W K Kiezun, Adam Lipskind, Shane Ng, Nicholas LiCausi, Joseph A Kim, Chloe S Brezina, Paul Tuschl, Thomas Maas, Richard Kearns, William G Williams, Zev |
| description | To explore restoration of ovarian function using epigenetically-related, induced pluripotent stem cells (iPSCs), we functionally evaluated the epigenetic memory of novel iPSC lines, derived from mouse and human ovarian granulosa cells (GCs) using c-Myc, Klf4, Sox2 and Oct4 retroviral vectors. The stem cell identity of the mouse and human GC-derived iPSCs (mGriPSCs, hGriPSCs) was verified by demonstrating embryonic stem cell (ESC) antigen expression using immunocytochemistry and RT-PCR analysis, as well as formation of embryoid bodies (EBs) and teratomas that are capable of differentiating into cells from all three germ layers. GriPSCs' gene expression profiles associate more closely with those of ESCs than of the originating GCs as demonstrated by genome-wide analysis of mRNA and microRNA. A comparative analysis of EBs generated from three different mouse cell lines (mGriPSCs; fibroblast-derived iPSC, mFiPSCs; G4 embryonic stem cells, G4 mESCs) revealed that differentiated mGriPSC-EBs synthesize 10-fold more estradiol (E2) than either differentiated FiPSC- or mESC-EBs under identical culture conditions. By contrast, mESC-EBs primarily synthesize progesterone (P4) and FiPSC-EBs produce neither E2 nor P4. Differentiated mGriPSC-EBs also express ovarian markers (AMHR, FSHR, Cyp19a1, ER and Inha) as well as markers of early gametogenesis (Mvh, Dazl, Gdf9, Boule and Zp1) more frequently than EBs of the other cell lines. These results provide evidence of preferential homotypic differentiation of mGriPSCs into ovarian cell types. Collectively, our data support the hypothesis that generating iPSCs from the desired tissue type may prove advantageous due to the iPSCs' epigenetic memory. |
| doi_str_mv | 10.1371/journal.pone.0119275 |
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The stem cell identity of the mouse and human GC-derived iPSCs (mGriPSCs, hGriPSCs) was verified by demonstrating embryonic stem cell (ESC) antigen expression using immunocytochemistry and RT-PCR analysis, as well as formation of embryoid bodies (EBs) and teratomas that are capable of differentiating into cells from all three germ layers. GriPSCs' gene expression profiles associate more closely with those of ESCs than of the originating GCs as demonstrated by genome-wide analysis of mRNA and microRNA. A comparative analysis of EBs generated from three different mouse cell lines (mGriPSCs; fibroblast-derived iPSC, mFiPSCs; G4 embryonic stem cells, G4 mESCs) revealed that differentiated mGriPSC-EBs synthesize 10-fold more estradiol (E2) than either differentiated FiPSC- or mESC-EBs under identical culture conditions. By contrast, mESC-EBs primarily synthesize progesterone (P4) and FiPSC-EBs produce neither E2 nor P4. Differentiated mGriPSC-EBs also express ovarian markers (AMHR, FSHR, Cyp19a1, ER and Inha) as well as markers of early gametogenesis (Mvh, Dazl, Gdf9, Boule and Zp1) more frequently than EBs of the other cell lines. These results provide evidence of preferential homotypic differentiation of mGriPSCs into ovarian cell types. Collectively, our data support the hypothesis that generating iPSCs from the desired tissue type may prove advantageous due to the iPSCs' epigenetic memory.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0119275</identifier><identifier>PMID: 25751620</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>17β-Estradiol ; Analysis ; Animals ; Biomarkers ; Biotechnology ; c-Myc protein ; Cell culture ; Cell Differentiation ; Cell lines ; Cells, Cultured ; Comparative analysis ; Differentiation ; Embryo cells ; Embryoid Bodies - cytology ; Embryoid Bodies - immunology ; Embryoid Bodies - metabolism ; Embryonic stem cells ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - immunology ; Embryonic Stem Cells - metabolism ; Embryos ; Epigenesis, Genetic ; Epigenetics ; Estradiol - metabolism ; Estrogen receptors ; Estrogens ; Female ; Gametogenesis ; Gene expression ; Genomes ; Germ Layers - cytology ; Germ Layers - immunology ; Germ Layers - metabolism ; Granulosa cells ; Granulosa Cells - cytology ; Humans ; Immunocytochemistry ; Induced Pluripotent Stem Cells - cytology ; Induced Pluripotent Stem Cells - immunology ; Induced Pluripotent Stem Cells - metabolism ; Infertility ; Influence ; KLF4 protein ; Kruppel-Like Transcription Factors - genetics ; Mice ; miRNA ; Myc protein ; Oct-4 protein ; Octamer Transcription Factor-3 - genetics ; Pluripotency ; Polymerase chain reaction ; Progesterone ; Progesterone - metabolism ; Proto-Oncogene Proteins c-myc - genetics ; Restoration ; Retroviridae - genetics ; Retroviridae - immunology ; Ribonucleic acid ; RNA ; Sex hormones ; SOXB1 Transcription Factors - genetics ; Stem cell research ; Stem cell transplantation ; Stem cells ; Synthesis</subject><ispartof>PloS one, 2015-03, Vol.10 (3), p.e0119275</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Anchan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Anchan et al 2015 Anchan et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-c655ea7d28a8357fc158854a35f2bdb198610208ea657fd8186403de272a380d3</citedby><cites>FETCH-LOGICAL-c692t-c655ea7d28a8357fc158854a35f2bdb198610208ea657fd8186403de272a380d3</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/PMC4353623/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353623/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25751620$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anchan, Raymond</creatorcontrib><creatorcontrib>Gerami-Naini, Behzad</creatorcontrib><creatorcontrib>Lindsey, Jennifer S</creatorcontrib><creatorcontrib>Ho, Joshua W K</creatorcontrib><creatorcontrib>Kiezun, Adam</creatorcontrib><creatorcontrib>Lipskind, Shane</creatorcontrib><creatorcontrib>Ng, Nicholas</creatorcontrib><creatorcontrib>LiCausi, Joseph A</creatorcontrib><creatorcontrib>Kim, Chloe S</creatorcontrib><creatorcontrib>Brezina, Paul</creatorcontrib><creatorcontrib>Tuschl, Thomas</creatorcontrib><creatorcontrib>Maas, Richard</creatorcontrib><creatorcontrib>Kearns, William G</creatorcontrib><creatorcontrib>Williams, Zev</creatorcontrib><title>Efficient differentiation of steroidogenic and germ-like cells from epigenetically-related iPSCs derived from ovarian granulosa cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>To explore restoration of ovarian function using epigenetically-related, induced pluripotent stem cells (iPSCs), we functionally evaluated the epigenetic memory of novel iPSC lines, derived from mouse and human ovarian granulosa cells (GCs) using c-Myc, Klf4, Sox2 and Oct4 retroviral vectors. The stem cell identity of the mouse and human GC-derived iPSCs (mGriPSCs, hGriPSCs) was verified by demonstrating embryonic stem cell (ESC) antigen expression using immunocytochemistry and RT-PCR analysis, as well as formation of embryoid bodies (EBs) and teratomas that are capable of differentiating into cells from all three germ layers. GriPSCs' gene expression profiles associate more closely with those of ESCs than of the originating GCs as demonstrated by genome-wide analysis of mRNA and microRNA. A comparative analysis of EBs generated from three different mouse cell lines (mGriPSCs; fibroblast-derived iPSC, mFiPSCs; G4 embryonic stem cells, G4 mESCs) revealed that differentiated mGriPSC-EBs synthesize 10-fold more estradiol (E2) than either differentiated FiPSC- or mESC-EBs under identical culture conditions. By contrast, mESC-EBs primarily synthesize progesterone (P4) and FiPSC-EBs produce neither E2 nor P4. Differentiated mGriPSC-EBs also express ovarian markers (AMHR, FSHR, Cyp19a1, ER and Inha) as well as markers of early gametogenesis (Mvh, Dazl, Gdf9, Boule and Zp1) more frequently than EBs of the other cell lines. These results provide evidence of preferential homotypic differentiation of mGriPSCs into ovarian cell types. Collectively, our data support the hypothesis that generating iPSCs from the desired tissue type may prove advantageous due to the iPSCs' epigenetic memory.</description><subject>17β-Estradiol</subject><subject>Analysis</subject><subject>Animals</subject><subject>Biomarkers</subject><subject>Biotechnology</subject><subject>c-Myc protein</subject><subject>Cell culture</subject><subject>Cell Differentiation</subject><subject>Cell lines</subject><subject>Cells, Cultured</subject><subject>Comparative analysis</subject><subject>Differentiation</subject><subject>Embryo cells</subject><subject>Embryoid Bodies - cytology</subject><subject>Embryoid Bodies - immunology</subject><subject>Embryoid Bodies - metabolism</subject><subject>Embryonic stem cells</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - immunology</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Embryos</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>Estradiol - metabolism</subject><subject>Estrogen receptors</subject><subject>Estrogens</subject><subject>Female</subject><subject>Gametogenesis</subject><subject>Gene expression</subject><subject>Genomes</subject><subject>Germ Layers - cytology</subject><subject>Germ Layers - immunology</subject><subject>Germ Layers - metabolism</subject><subject>Granulosa cells</subject><subject>Granulosa Cells - cytology</subject><subject>Humans</subject><subject>Immunocytochemistry</subject><subject>Induced Pluripotent Stem Cells - cytology</subject><subject>Induced Pluripotent Stem Cells - immunology</subject><subject>Induced Pluripotent Stem Cells - metabolism</subject><subject>Infertility</subject><subject>Influence</subject><subject>KLF4 protein</subject><subject>Kruppel-Like Transcription Factors - genetics</subject><subject>Mice</subject><subject>miRNA</subject><subject>Myc protein</subject><subject>Oct-4 protein</subject><subject>Octamer Transcription Factor-3 - genetics</subject><subject>Pluripotency</subject><subject>Polymerase chain reaction</subject><subject>Progesterone</subject><subject>Progesterone - metabolism</subject><subject>Proto-Oncogene Proteins c-myc - genetics</subject><subject>Restoration</subject><subject>Retroviridae - genetics</subject><subject>Retroviridae - immunology</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Sex hormones</subject><subject>SOXB1 Transcription Factors - genetics</subject><subject>Stem cell research</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Synthesis</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9GK1DAUhoso7rr6BqIFQfBixiZp0vZGWIZVBxZWXPU2nGlOOhnTZjZpB_cBfG8zO91lCgpSSJOc7_xJfs5JkpckmxNWkPcbN_gO7HzrOpxnhFS04I-SU1IxOhM0Y4-P5ifJsxA2WcZZKcTT5ITygpMYOE1-X2htaoNdnyqjNfo4M9Ab16VOp6FH74xyDXamTqFTaYO-nVnzE9MarQ2p9q5NcWsigb2pwdrbmUcLParUfLlehFShN7u4uiPdDryBLm08dIN1AQ4yz5MnGmzAF-P_LPn-8eLb4vPs8urTcnF-OatFRfs4co5QKFpCyXiha8LLkufAuKYrtSJVKUhGsxJBxKgqSSnyjCmkBQVWZoqdJa8Putt4thwdDJIIQXgloiuRWB4I5WAjt9604G-lAyPvNpxvJPj4UIuSZasCqSZCFZhDpUFzUVcoSgAuBF1FrQ_jacOqRVVHaz3Yieg00pm1bNxO5owzQVkUeDMKeHczYOj_ceWRaiDeynTaRbG6NaGW5zmtKM9pTiM1_wsVP4WtqWMNaRP3JwnvJgmR6fFX38AQglxef_1_9urHlH17xK4RbL8Ozg77mgtTMD-AtXcheNQPzpFM7lvg3g25bwE5tkBMe3Xs-kPSfc2zP3IgA1Y</recordid><startdate>20150309</startdate><enddate>20150309</enddate><creator>Anchan, Raymond</creator><creator>Gerami-Naini, Behzad</creator><creator>Lindsey, Jennifer S</creator><creator>Ho, Joshua W K</creator><creator>Kiezun, Adam</creator><creator>Lipskind, Shane</creator><creator>Ng, Nicholas</creator><creator>LiCausi, Joseph A</creator><creator>Kim, Chloe S</creator><creator>Brezina, Paul</creator><creator>Tuschl, Thomas</creator><creator>Maas, Richard</creator><creator>Kearns, William G</creator><creator>Williams, Zev</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</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>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150309</creationdate><title>Efficient differentiation of steroidogenic and germ-like cells from epigenetically-related iPSCs derived from ovarian granulosa cells</title><author>Anchan, Raymond ; Gerami-Naini, Behzad ; Lindsey, Jennifer S ; Ho, Joshua W K ; Kiezun, Adam ; Lipskind, Shane ; Ng, Nicholas ; LiCausi, Joseph A ; Kim, Chloe S ; Brezina, Paul ; Tuschl, Thomas ; Maas, Richard ; Kearns, William G ; Williams, Zev</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-c655ea7d28a8357fc158854a35f2bdb198610208ea657fd8186403de272a380d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>17β-Estradiol</topic><topic>Analysis</topic><topic>Animals</topic><topic>Biomarkers</topic><topic>Biotechnology</topic><topic>c-Myc protein</topic><topic>Cell culture</topic><topic>Cell Differentiation</topic><topic>Cell lines</topic><topic>Cells, Cultured</topic><topic>Comparative analysis</topic><topic>Differentiation</topic><topic>Embryo cells</topic><topic>Embryoid Bodies - cytology</topic><topic>Embryoid Bodies - immunology</topic><topic>Embryoid Bodies - metabolism</topic><topic>Embryonic stem cells</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Embryonic Stem Cells - immunology</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>Embryos</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetics</topic><topic>Estradiol - metabolism</topic><topic>Estrogen receptors</topic><topic>Estrogens</topic><topic>Female</topic><topic>Gametogenesis</topic><topic>Gene expression</topic><topic>Genomes</topic><topic>Germ Layers - cytology</topic><topic>Germ Layers - immunology</topic><topic>Germ Layers - metabolism</topic><topic>Granulosa cells</topic><topic>Granulosa Cells - cytology</topic><topic>Humans</topic><topic>Immunocytochemistry</topic><topic>Induced Pluripotent Stem Cells - cytology</topic><topic>Induced Pluripotent Stem Cells - immunology</topic><topic>Induced Pluripotent Stem Cells - metabolism</topic><topic>Infertility</topic><topic>Influence</topic><topic>KLF4 protein</topic><topic>Kruppel-Like Transcription Factors - genetics</topic><topic>Mice</topic><topic>miRNA</topic><topic>Myc protein</topic><topic>Oct-4 protein</topic><topic>Octamer Transcription Factor-3 - genetics</topic><topic>Pluripotency</topic><topic>Polymerase chain reaction</topic><topic>Progesterone</topic><topic>Progesterone - metabolism</topic><topic>Proto-Oncogene Proteins c-myc - genetics</topic><topic>Restoration</topic><topic>Retroviridae - genetics</topic><topic>Retroviridae - immunology</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Sex hormones</topic><topic>SOXB1 Transcription Factors - genetics</topic><topic>Stem cell research</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Synthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Anchan, Raymond</creatorcontrib><creatorcontrib>Gerami-Naini, Behzad</creatorcontrib><creatorcontrib>Lindsey, Jennifer S</creatorcontrib><creatorcontrib>Ho, Joshua W K</creatorcontrib><creatorcontrib>Kiezun, Adam</creatorcontrib><creatorcontrib>Lipskind, Shane</creatorcontrib><creatorcontrib>Ng, Nicholas</creatorcontrib><creatorcontrib>LiCausi, Joseph A</creatorcontrib><creatorcontrib>Kim, Chloe S</creatorcontrib><creatorcontrib>Brezina, Paul</creatorcontrib><creatorcontrib>Tuschl, Thomas</creatorcontrib><creatorcontrib>Maas, Richard</creatorcontrib><creatorcontrib>Kearns, William G</creatorcontrib><creatorcontrib>Williams, Zev</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: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</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>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</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>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Anchan, Raymond</au><au>Gerami-Naini, Behzad</au><au>Lindsey, Jennifer S</au><au>Ho, Joshua W K</au><au>Kiezun, Adam</au><au>Lipskind, Shane</au><au>Ng, Nicholas</au><au>LiCausi, Joseph A</au><au>Kim, Chloe S</au><au>Brezina, Paul</au><au>Tuschl, Thomas</au><au>Maas, Richard</au><au>Kearns, William G</au><au>Williams, Zev</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficient differentiation of steroidogenic and germ-like cells from epigenetically-related iPSCs derived from ovarian granulosa cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-03-09</date><risdate>2015</risdate><volume>10</volume><issue>3</issue><spage>e0119275</spage><pages>e0119275-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>To explore restoration of ovarian function using epigenetically-related, induced pluripotent stem cells (iPSCs), we functionally evaluated the epigenetic memory of novel iPSC lines, derived from mouse and human ovarian granulosa cells (GCs) using c-Myc, Klf4, Sox2 and Oct4 retroviral vectors. The stem cell identity of the mouse and human GC-derived iPSCs (mGriPSCs, hGriPSCs) was verified by demonstrating embryonic stem cell (ESC) antigen expression using immunocytochemistry and RT-PCR analysis, as well as formation of embryoid bodies (EBs) and teratomas that are capable of differentiating into cells from all three germ layers. GriPSCs' gene expression profiles associate more closely with those of ESCs than of the originating GCs as demonstrated by genome-wide analysis of mRNA and microRNA. A comparative analysis of EBs generated from three different mouse cell lines (mGriPSCs; fibroblast-derived iPSC, mFiPSCs; G4 embryonic stem cells, G4 mESCs) revealed that differentiated mGriPSC-EBs synthesize 10-fold more estradiol (E2) than either differentiated FiPSC- or mESC-EBs under identical culture conditions. By contrast, mESC-EBs primarily synthesize progesterone (P4) and FiPSC-EBs produce neither E2 nor P4. Differentiated mGriPSC-EBs also express ovarian markers (AMHR, FSHR, Cyp19a1, ER and Inha) as well as markers of early gametogenesis (Mvh, Dazl, Gdf9, Boule and Zp1) more frequently than EBs of the other cell lines. These results provide evidence of preferential homotypic differentiation of mGriPSCs into ovarian cell types. Collectively, our data support the hypothesis that generating iPSCs from the desired tissue type may prove advantageous due to the iPSCs' epigenetic memory.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25751620</pmid><doi>10.1371/journal.pone.0119275</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-03, Vol.10 (3), p.e0119275 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1661596257 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | 17β-Estradiol Analysis Animals Biomarkers Biotechnology c-Myc protein Cell culture Cell Differentiation Cell lines Cells, Cultured Comparative analysis Differentiation Embryo cells Embryoid Bodies - cytology Embryoid Bodies - immunology Embryoid Bodies - metabolism Embryonic stem cells Embryonic Stem Cells - cytology Embryonic Stem Cells - immunology Embryonic Stem Cells - metabolism Embryos Epigenesis, Genetic Epigenetics Estradiol - metabolism Estrogen receptors Estrogens Female Gametogenesis Gene expression Genomes Germ Layers - cytology Germ Layers - immunology Germ Layers - metabolism Granulosa cells Granulosa Cells - cytology Humans Immunocytochemistry Induced Pluripotent Stem Cells - cytology Induced Pluripotent Stem Cells - immunology Induced Pluripotent Stem Cells - metabolism Infertility Influence KLF4 protein Kruppel-Like Transcription Factors - genetics Mice miRNA Myc protein Oct-4 protein Octamer Transcription Factor-3 - genetics Pluripotency Polymerase chain reaction Progesterone Progesterone - metabolism Proto-Oncogene Proteins c-myc - genetics Restoration Retroviridae - genetics Retroviridae - immunology Ribonucleic acid RNA Sex hormones SOXB1 Transcription Factors - genetics Stem cell research Stem cell transplantation Stem cells Synthesis |
| title | Efficient differentiation of steroidogenic and germ-like cells from epigenetically-related iPSCs derived from ovarian granulosa cells |
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