Integrated transcriptome and binding sites analysis implicates E2F in the regulation of self-renewal in human pluripotent stem cells
Rapid cellular growth and multiplication, limited replicative senescence, calibrated sensitivity to apoptosis, and a capacity to differentiate into almost any cell type are major properties that underline the self-renewal capabilities of human pluripotent stem cells (hPSCs). We developed an integrat...
Gespeichert in:
Veröffentlicht in: | PloS one 2011-11, Vol.6 (11), p.e27231-e27231 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | e27231 |
---|---|
container_issue | 11 |
container_start_page | e27231 |
container_title | PloS one |
container_volume | 6 |
creator | Yeo, Hock Chuan Beh, Thian Thian Quek, Jovina Jia Ling Koh, Geoffrey Chan, Ken Kwok Keung Lee, Dong-Yup |
description | Rapid cellular growth and multiplication, limited replicative senescence, calibrated sensitivity to apoptosis, and a capacity to differentiate into almost any cell type are major properties that underline the self-renewal capabilities of human pluripotent stem cells (hPSCs). We developed an integrated bioinformatics pipeline to understand the gene regulation and functions involved in maintaining such self-renewal properties of hPSCs compared to matched fibroblasts. An initial genome-wide screening of transcription factor activity using in silico binding-site and gene expression microarray data newly identified E2F as one of major candidate factors, revealing their significant regulation of the transcriptome. This is underscored by an elevated level of its transcription factor activity and expression in all tested pluripotent stem cell lines. Subsequent analysis of functional gene groups demonstrated the importance of the TFs to self-renewal in the pluripotency-coupled context; E2F directly targets the global signaling (e.g. self-renewal associated WNT and FGF pathways) and metabolic network (e.g. energy generation pathways, molecular transports and fatty acid metabolism) to promote its canonical functions that are driving the self-renewal of hPSCs. In addition, we proposed a core self-renewal module of regulatory interplay between E2F and, WNT and FGF pathways in these cells. Thus, we conclude that E2F plays a significant role in influencing the self-renewal capabilities of hPSCs. |
doi_str_mv | 10.1371/journal.pone.0027231 |
format | Article |
fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1310933638</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A476863465</galeid><doaj_id>oai_doaj_org_article_80176bfd331747cdbe27f6e8c02fd493</doaj_id><sourcerecordid>A476863465</sourcerecordid><originalsourceid>FETCH-LOGICAL-c691t-25984e1b58c33ff74ff38cee50e64df1a1f75e9255cc804fcaf3645fd46eae93</originalsourceid><addsrcrecordid>eNqNk11rFDEUhgdRbK3-A9GAoHixa74mM3MjlNLqQqGgxduQzZzMpmSSNcmovfeHm7Hb0pVeSC4STp7zno_kVNVLgpeENeTDVZiiV265DR6WGNOGMvKoOiQdowtBMXt873xQPUvpCuOatUI8rQ4oxY0grDusfq98hiGqDD3KUfmko93mMAJSvkdr63vrB5RshlQsyl0nm5Adt85qNdtO6RmyHuUNoAjD5FS2waNgUAJnFhE8_FRuJjbTqDzauqnohww-o5RhRBqcS8-rJ0a5BC92-1F1eXZ6efJ5cX7xaXVyfL7QoiN5Qeuu5UDWdasZM6bhxrBWA9QYBO8NUcQ0NXS0rrVuMTdaGSZ4bXouQEHHjqrXN7JbF5Lc9S9JwgjuGBOsLcTqhuiDupLbaEcVr2VQVv41hDhIFbPVDmSLSSPWpmeMNLzR_RpoYwS0GtMSsOgdVR930ab1CL0uJUfl9kT3b7zdyCH8kIziVtA5mXc7gRi-T5CyHG2a-6U8hCnJDnNcMue8kG_-IR8ubkcNquRvvQklrJ415TFvRCsYF3Whlg9QZfUwWl3-mrHFvufwfs-hMBl-5UFNKcnV1y__z15822ff3mM3oFzepOCm-YOlfZDfgDqGlCKYux4TLOdRue2GnEdF7kaluL26_z53Trezwf4ANN0RIw</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1310933638</pqid></control><display><type>article</type><title>Integrated transcriptome and binding sites analysis implicates E2F in the regulation of self-renewal in human pluripotent stem cells</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Yeo, Hock Chuan ; Beh, Thian Thian ; Quek, Jovina Jia Ling ; Koh, Geoffrey ; Chan, Ken Kwok Keung ; Lee, Dong-Yup</creator><contributor>Selvarajoo, Kumar</contributor><creatorcontrib>Yeo, Hock Chuan ; Beh, Thian Thian ; Quek, Jovina Jia Ling ; Koh, Geoffrey ; Chan, Ken Kwok Keung ; Lee, Dong-Yup ; Selvarajoo, Kumar</creatorcontrib><description>Rapid cellular growth and multiplication, limited replicative senescence, calibrated sensitivity to apoptosis, and a capacity to differentiate into almost any cell type are major properties that underline the self-renewal capabilities of human pluripotent stem cells (hPSCs). We developed an integrated bioinformatics pipeline to understand the gene regulation and functions involved in maintaining such self-renewal properties of hPSCs compared to matched fibroblasts. An initial genome-wide screening of transcription factor activity using in silico binding-site and gene expression microarray data newly identified E2F as one of major candidate factors, revealing their significant regulation of the transcriptome. This is underscored by an elevated level of its transcription factor activity and expression in all tested pluripotent stem cell lines. Subsequent analysis of functional gene groups demonstrated the importance of the TFs to self-renewal in the pluripotency-coupled context; E2F directly targets the global signaling (e.g. self-renewal associated WNT and FGF pathways) and metabolic network (e.g. energy generation pathways, molecular transports and fatty acid metabolism) to promote its canonical functions that are driving the self-renewal of hPSCs. In addition, we proposed a core self-renewal module of regulatory interplay between E2F and, WNT and FGF pathways in these cells. Thus, we conclude that E2F plays a significant role in influencing the self-renewal capabilities of hPSCs.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0027231</identifier><identifier>PMID: 22076139</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Apoptosis ; Binding Sites ; Bioinformatics ; Biology ; Biomarkers - metabolism ; Blotting, Western ; Cell cycle ; Cell Differentiation ; Cell lines ; Cell Proliferation ; Cell self-renewal ; Cells, Cultured ; DNA microarrays ; E2F protein ; E2F1 Transcription Factor - genetics ; E2F1 Transcription Factor - metabolism ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - metabolism ; Fatty acids ; Fibroblast growth factors ; Fibroblasts ; Fibroblasts - cytology ; Fibroblasts - metabolism ; Gene expression ; Gene Expression Profiling ; Gene regulation ; Genes ; Genetic aspects ; Genomes ; Genomics ; Growth factors ; Humans ; Luciferases - metabolism ; Metabolism ; Oligonucleotide Array Sequence Analysis ; Pluripotency ; Pluripotent Stem Cells - cytology ; Pluripotent Stem Cells - metabolism ; Proteins ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; Science ; Senescence ; Signal Transduction ; Signaling ; Stem cells ; Transcription (Genetics) ; Transcription factors ; Wnt protein</subject><ispartof>PloS one, 2011-11, Vol.6 (11), p.e27231-e27231</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Yeo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>Yeo et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-25984e1b58c33ff74ff38cee50e64df1a1f75e9255cc804fcaf3645fd46eae93</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208628/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208628/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22076139$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Selvarajoo, Kumar</contributor><creatorcontrib>Yeo, Hock Chuan</creatorcontrib><creatorcontrib>Beh, Thian Thian</creatorcontrib><creatorcontrib>Quek, Jovina Jia Ling</creatorcontrib><creatorcontrib>Koh, Geoffrey</creatorcontrib><creatorcontrib>Chan, Ken Kwok Keung</creatorcontrib><creatorcontrib>Lee, Dong-Yup</creatorcontrib><title>Integrated transcriptome and binding sites analysis implicates E2F in the regulation of self-renewal in human pluripotent stem cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Rapid cellular growth and multiplication, limited replicative senescence, calibrated sensitivity to apoptosis, and a capacity to differentiate into almost any cell type are major properties that underline the self-renewal capabilities of human pluripotent stem cells (hPSCs). We developed an integrated bioinformatics pipeline to understand the gene regulation and functions involved in maintaining such self-renewal properties of hPSCs compared to matched fibroblasts. An initial genome-wide screening of transcription factor activity using in silico binding-site and gene expression microarray data newly identified E2F as one of major candidate factors, revealing their significant regulation of the transcriptome. This is underscored by an elevated level of its transcription factor activity and expression in all tested pluripotent stem cell lines. Subsequent analysis of functional gene groups demonstrated the importance of the TFs to self-renewal in the pluripotency-coupled context; E2F directly targets the global signaling (e.g. self-renewal associated WNT and FGF pathways) and metabolic network (e.g. energy generation pathways, molecular transports and fatty acid metabolism) to promote its canonical functions that are driving the self-renewal of hPSCs. In addition, we proposed a core self-renewal module of regulatory interplay between E2F and, WNT and FGF pathways in these cells. Thus, we conclude that E2F plays a significant role in influencing the self-renewal capabilities of hPSCs.</description><subject>Apoptosis</subject><subject>Binding Sites</subject><subject>Bioinformatics</subject><subject>Biology</subject><subject>Biomarkers - metabolism</subject><subject>Blotting, Western</subject><subject>Cell cycle</subject><subject>Cell Differentiation</subject><subject>Cell lines</subject><subject>Cell Proliferation</subject><subject>Cell self-renewal</subject><subject>Cells, Cultured</subject><subject>DNA microarrays</subject><subject>E2F protein</subject><subject>E2F1 Transcription Factor - genetics</subject><subject>E2F1 Transcription Factor - metabolism</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Fatty acids</subject><subject>Fibroblast growth factors</subject><subject>Fibroblasts</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - metabolism</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Luciferases - metabolism</subject><subject>Metabolism</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Pluripotency</subject><subject>Pluripotent Stem Cells - cytology</subject><subject>Pluripotent Stem Cells - metabolism</subject><subject>Proteins</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>Science</subject><subject>Senescence</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Stem cells</subject><subject>Transcription (Genetics)</subject><subject>Transcription factors</subject><subject>Wnt protein</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</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><sourceid>DOA</sourceid><recordid>eNqNk11rFDEUhgdRbK3-A9GAoHixa74mM3MjlNLqQqGgxduQzZzMpmSSNcmovfeHm7Hb0pVeSC4STp7zno_kVNVLgpeENeTDVZiiV265DR6WGNOGMvKoOiQdowtBMXt873xQPUvpCuOatUI8rQ4oxY0grDusfq98hiGqDD3KUfmko93mMAJSvkdr63vrB5RshlQsyl0nm5Adt85qNdtO6RmyHuUNoAjD5FS2waNgUAJnFhE8_FRuJjbTqDzauqnohww-o5RhRBqcS8-rJ0a5BC92-1F1eXZ6efJ5cX7xaXVyfL7QoiN5Qeuu5UDWdasZM6bhxrBWA9QYBO8NUcQ0NXS0rrVuMTdaGSZ4bXouQEHHjqrXN7JbF5Lc9S9JwgjuGBOsLcTqhuiDupLbaEcVr2VQVv41hDhIFbPVDmSLSSPWpmeMNLzR_RpoYwS0GtMSsOgdVR930ab1CL0uJUfl9kT3b7zdyCH8kIziVtA5mXc7gRi-T5CyHG2a-6U8hCnJDnNcMue8kG_-IR8ubkcNquRvvQklrJ415TFvRCsYF3Whlg9QZfUwWl3-mrHFvufwfs-hMBl-5UFNKcnV1y__z15822ff3mM3oFzepOCm-YOlfZDfgDqGlCKYux4TLOdRue2GnEdF7kaluL26_z53Trezwf4ANN0RIw</recordid><startdate>20111104</startdate><enddate>20111104</enddate><creator>Yeo, Hock Chuan</creator><creator>Beh, Thian Thian</creator><creator>Quek, Jovina Jia Ling</creator><creator>Koh, Geoffrey</creator><creator>Chan, Ken Kwok Keung</creator><creator>Lee, Dong-Yup</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>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>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20111104</creationdate><title>Integrated transcriptome and binding sites analysis implicates E2F in the regulation of self-renewal in human pluripotent stem cells</title><author>Yeo, Hock Chuan ; Beh, Thian Thian ; Quek, Jovina Jia Ling ; Koh, Geoffrey ; Chan, Ken Kwok Keung ; Lee, Dong-Yup</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c691t-25984e1b58c33ff74ff38cee50e64df1a1f75e9255cc804fcaf3645fd46eae93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Apoptosis</topic><topic>Binding Sites</topic><topic>Bioinformatics</topic><topic>Biology</topic><topic>Biomarkers - metabolism</topic><topic>Blotting, Western</topic><topic>Cell cycle</topic><topic>Cell Differentiation</topic><topic>Cell lines</topic><topic>Cell Proliferation</topic><topic>Cell self-renewal</topic><topic>Cells, Cultured</topic><topic>DNA microarrays</topic><topic>E2F protein</topic><topic>E2F1 Transcription Factor - genetics</topic><topic>E2F1 Transcription Factor - metabolism</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>Fatty acids</topic><topic>Fibroblast growth factors</topic><topic>Fibroblasts</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - metabolism</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene regulation</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Luciferases - metabolism</topic><topic>Metabolism</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Pluripotency</topic><topic>Pluripotent Stem Cells - cytology</topic><topic>Pluripotent Stem Cells - metabolism</topic><topic>Proteins</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>Science</topic><topic>Senescence</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Stem cells</topic><topic>Transcription (Genetics)</topic><topic>Transcription factors</topic><topic>Wnt protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yeo, Hock Chuan</creatorcontrib><creatorcontrib>Beh, Thian Thian</creatorcontrib><creatorcontrib>Quek, Jovina Jia Ling</creatorcontrib><creatorcontrib>Koh, Geoffrey</creatorcontrib><creatorcontrib>Chan, Ken Kwok Keung</creatorcontrib><creatorcontrib>Lee, Dong-Yup</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 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>MEDLINE - Academic</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>Yeo, Hock Chuan</au><au>Beh, Thian Thian</au><au>Quek, Jovina Jia Ling</au><au>Koh, Geoffrey</au><au>Chan, Ken Kwok Keung</au><au>Lee, Dong-Yup</au><au>Selvarajoo, Kumar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Integrated transcriptome and binding sites analysis implicates E2F in the regulation of self-renewal in human pluripotent stem cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-11-04</date><risdate>2011</risdate><volume>6</volume><issue>11</issue><spage>e27231</spage><epage>e27231</epage><pages>e27231-e27231</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Rapid cellular growth and multiplication, limited replicative senescence, calibrated sensitivity to apoptosis, and a capacity to differentiate into almost any cell type are major properties that underline the self-renewal capabilities of human pluripotent stem cells (hPSCs). We developed an integrated bioinformatics pipeline to understand the gene regulation and functions involved in maintaining such self-renewal properties of hPSCs compared to matched fibroblasts. An initial genome-wide screening of transcription factor activity using in silico binding-site and gene expression microarray data newly identified E2F as one of major candidate factors, revealing their significant regulation of the transcriptome. This is underscored by an elevated level of its transcription factor activity and expression in all tested pluripotent stem cell lines. Subsequent analysis of functional gene groups demonstrated the importance of the TFs to self-renewal in the pluripotency-coupled context; E2F directly targets the global signaling (e.g. self-renewal associated WNT and FGF pathways) and metabolic network (e.g. energy generation pathways, molecular transports and fatty acid metabolism) to promote its canonical functions that are driving the self-renewal of hPSCs. In addition, we proposed a core self-renewal module of regulatory interplay between E2F and, WNT and FGF pathways in these cells. Thus, we conclude that E2F plays a significant role in influencing the self-renewal capabilities of hPSCs.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22076139</pmid><doi>10.1371/journal.pone.0027231</doi><tpages>e27231</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2011-11, Vol.6 (11), p.e27231-e27231 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1310933638 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Apoptosis Binding Sites Bioinformatics Biology Biomarkers - metabolism Blotting, Western Cell cycle Cell Differentiation Cell lines Cell Proliferation Cell self-renewal Cells, Cultured DNA microarrays E2F protein E2F1 Transcription Factor - genetics E2F1 Transcription Factor - metabolism Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Fatty acids Fibroblast growth factors Fibroblasts Fibroblasts - cytology Fibroblasts - metabolism Gene expression Gene Expression Profiling Gene regulation Genes Genetic aspects Genomes Genomics Growth factors Humans Luciferases - metabolism Metabolism Oligonucleotide Array Sequence Analysis Pluripotency Pluripotent Stem Cells - cytology Pluripotent Stem Cells - metabolism Proteins Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics Science Senescence Signal Transduction Signaling Stem cells Transcription (Genetics) Transcription factors Wnt protein |
title | Integrated transcriptome and binding sites analysis implicates E2F in the regulation of self-renewal in human pluripotent stem cells |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T11%3A38%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Integrated%20transcriptome%20and%20binding%20sites%20analysis%20implicates%20E2F%20in%20the%20regulation%20of%20self-renewal%20in%20human%20pluripotent%20stem%20cells&rft.jtitle=PloS%20one&rft.au=Yeo,%20Hock%20Chuan&rft.date=2011-11-04&rft.volume=6&rft.issue=11&rft.spage=e27231&rft.epage=e27231&rft.pages=e27231-e27231&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0027231&rft_dat=%3Cgale_plos_%3EA476863465%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1310933638&rft_id=info:pmid/22076139&rft_galeid=A476863465&rft_doaj_id=oai_doaj_org_article_80176bfd331747cdbe27f6e8c02fd493&rfr_iscdi=true |