Targeted RNA N 6 -Methyladenosine Demethylation Controls Cell Fate Transition in Human Pluripotent Stem Cells
Deficiency of the N -methyladenosine (m A) methyltransferase complex results in global reduction of m A abundance and defective cell development in embryonic stem cells (ESCs). However, it's unclear whether regional m A methylation affects cell fate decisions due to the inability to modulate in...
Gespeichert in:
| Veröffentlicht in: | Advanced science 2021-06, Vol.8 (11), p.e2003902 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 11 |
| container_start_page | e2003902 |
| container_title | Advanced science |
| container_volume | 8 |
| creator | Chen, Xuena Zhao, Qingquan Zhao, Yu-Li Chai, Guo-Shi Cheng, Weisheng Zhao, Zhiju Wang, Jia Luo, Guan-Zheng Cao, Nan |
| description | Deficiency of the N
-methyladenosine (m
A) methyltransferase complex results in global reduction of m
A abundance and defective cell development in embryonic stem cells (ESCs). However, it's unclear whether regional m
A methylation affects cell fate decisions due to the inability to modulate individual m
A modification in ESCs with precise temporal control. Here, a targeted RNA m
A erasure (TRME) system is developed to achieve site-specific demethylation of RNAs in human ESCs (hESCs). TRME, in which a stably transfected, doxycycline-inducible dCas13a is fused to the catalytic domain of ALKBH5, can precisely and reversibly demethylate the targeted m
A site of mRNA and increase mRNA stability with limited off-target effects. It is further demonstrated that temporal m
A erasure on a single site of SOX2 is sufficient to control the differentiation of hESCs. This study provides a versatile toolbox to reveal the function of individual m
A modification in hESCs, enabling cell fate control studies at the epitranscriptional level. |
| doi_str_mv | 10.1002/advs.202003902 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8188216</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2539041175</sourcerecordid><originalsourceid>FETCH-LOGICAL-c315t-523595848d631324a766f4121364ed631221cb7830ef8a8bf79835a146668f8f3</originalsourceid><addsrcrecordid>eNpVUU1LAzEQDaKoVK8eJeB5ayZfm70IpVoV_ELrOaTdrG7ZTWqSLfjv3Votepph3ps3j3kInQAZAiH03JSrOKSEEsIKQnfQIYVCZUxxvvunP0DHMS4IISBYzkHtowPGgQiaF4eonZrwZpMt8fPDCD9gibN7m94_G1Na52PtLL607WaSau_w2LsUfBPx2DYNnphk8TQYF-tvtHb4pmuNw09NF-qlT9Yl_JJs-02PR2ivMk20xz91gF4nV9PxTXb3eH07Ht1lcwYiZYIyUQjFVSkZMMpNLmXFgQKT3K5nlMJ8litGbKWMmlV5oZgwwKWUqlIVG6CLje6ym7W2nPcugmn0MtStCZ_am1r_R1z9rt_8SitQioLsBc5-BIL_6GxMeuG74HrPmor-2RwgFz1ruGHNg48x2Gp7AYheJ6TXCeltQv3C6V9fW_pvHuwLhAKLwg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2539041175</pqid></control><display><type>article</type><title>Targeted RNA N 6 -Methyladenosine Demethylation Controls Cell Fate Transition in Human Pluripotent Stem Cells</title><source>PubMed (Medline)</source><source>MEDLINE</source><source>Wiley Online Library Journals</source><source>DOAJ Directory of Open Access Journals</source><source>Wiley Online Library (Open Access Collection)</source><source>EZB Electronic Journals Library</source><creator>Chen, Xuena ; Zhao, Qingquan ; Zhao, Yu-Li ; Chai, Guo-Shi ; Cheng, Weisheng ; Zhao, Zhiju ; Wang, Jia ; Luo, Guan-Zheng ; Cao, Nan</creator><creatorcontrib>Chen, Xuena ; Zhao, Qingquan ; Zhao, Yu-Li ; Chai, Guo-Shi ; Cheng, Weisheng ; Zhao, Zhiju ; Wang, Jia ; Luo, Guan-Zheng ; Cao, Nan</creatorcontrib><description>Deficiency of the N
-methyladenosine (m
A) methyltransferase complex results in global reduction of m
A abundance and defective cell development in embryonic stem cells (ESCs). However, it's unclear whether regional m
A methylation affects cell fate decisions due to the inability to modulate individual m
A modification in ESCs with precise temporal control. Here, a targeted RNA m
A erasure (TRME) system is developed to achieve site-specific demethylation of RNAs in human ESCs (hESCs). TRME, in which a stably transfected, doxycycline-inducible dCas13a is fused to the catalytic domain of ALKBH5, can precisely and reversibly demethylate the targeted m
A site of mRNA and increase mRNA stability with limited off-target effects. It is further demonstrated that temporal m
A erasure on a single site of SOX2 is sufficient to control the differentiation of hESCs. This study provides a versatile toolbox to reveal the function of individual m
A modification in hESCs, enabling cell fate control studies at the epitranscriptional level.</description><identifier>ISSN: 2198-3844</identifier><identifier>EISSN: 2198-3844</identifier><identifier>DOI: 10.1002/advs.202003902</identifier><identifier>PMID: 34105279</identifier><language>eng</language><publisher>Germany: John Wiley & Sons, Inc</publisher><subject>Adenosine - analogs & derivatives ; Adenosine - genetics ; AlkB Homolog 5, RNA Demethylase - genetics ; Caspases - genetics ; Catalytic Domain - genetics ; Cell Differentiation - genetics ; Cell Lineage - genetics ; Cell Proliferation - genetics ; Communication ; Communications ; CRISPR ; Cytoplasm ; Demethylation ; Editors ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - metabolism ; Humans ; Localization ; Methylation ; Methyltransferases - genetics ; Mutation ; Pluripotent Stem Cells - metabolism ; Proteins ; RNA Stability - genetics ; RNA, Messenger - genetics ; SOXB1 Transcription Factors - genetics ; Stem cells</subject><ispartof>Advanced science, 2021-06, Vol.8 (11), p.e2003902</ispartof><rights>2021 The Authors. Advanced Science published by Wiley-VCH GmbH.</rights><rights>2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 The Authors. Advanced Science published by Wiley‐VCH GmbH</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c315t-523595848d631324a766f4121364ed631221cb7830ef8a8bf79835a146668f8f3</citedby><cites>FETCH-LOGICAL-c315t-523595848d631324a766f4121364ed631221cb7830ef8a8bf79835a146668f8f3</cites><orcidid>0000-0002-1660-4728</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188216/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188216/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34105279$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Xuena</creatorcontrib><creatorcontrib>Zhao, Qingquan</creatorcontrib><creatorcontrib>Zhao, Yu-Li</creatorcontrib><creatorcontrib>Chai, Guo-Shi</creatorcontrib><creatorcontrib>Cheng, Weisheng</creatorcontrib><creatorcontrib>Zhao, Zhiju</creatorcontrib><creatorcontrib>Wang, Jia</creatorcontrib><creatorcontrib>Luo, Guan-Zheng</creatorcontrib><creatorcontrib>Cao, Nan</creatorcontrib><title>Targeted RNA N 6 -Methyladenosine Demethylation Controls Cell Fate Transition in Human Pluripotent Stem Cells</title><title>Advanced science</title><addtitle>Adv Sci (Weinh)</addtitle><description>Deficiency of the N
-methyladenosine (m
A) methyltransferase complex results in global reduction of m
A abundance and defective cell development in embryonic stem cells (ESCs). However, it's unclear whether regional m
A methylation affects cell fate decisions due to the inability to modulate individual m
A modification in ESCs with precise temporal control. Here, a targeted RNA m
A erasure (TRME) system is developed to achieve site-specific demethylation of RNAs in human ESCs (hESCs). TRME, in which a stably transfected, doxycycline-inducible dCas13a is fused to the catalytic domain of ALKBH5, can precisely and reversibly demethylate the targeted m
A site of mRNA and increase mRNA stability with limited off-target effects. It is further demonstrated that temporal m
A erasure on a single site of SOX2 is sufficient to control the differentiation of hESCs. This study provides a versatile toolbox to reveal the function of individual m
A modification in hESCs, enabling cell fate control studies at the epitranscriptional level.</description><subject>Adenosine - analogs & derivatives</subject><subject>Adenosine - genetics</subject><subject>AlkB Homolog 5, RNA Demethylase - genetics</subject><subject>Caspases - genetics</subject><subject>Catalytic Domain - genetics</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Lineage - genetics</subject><subject>Cell Proliferation - genetics</subject><subject>Communication</subject><subject>Communications</subject><subject>CRISPR</subject><subject>Cytoplasm</subject><subject>Demethylation</subject><subject>Editors</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Humans</subject><subject>Localization</subject><subject>Methylation</subject><subject>Methyltransferases - genetics</subject><subject>Mutation</subject><subject>Pluripotent Stem Cells - metabolism</subject><subject>Proteins</subject><subject>RNA Stability - genetics</subject><subject>RNA, Messenger - genetics</subject><subject>SOXB1 Transcription Factors - genetics</subject><subject>Stem cells</subject><issn>2198-3844</issn><issn>2198-3844</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpVUU1LAzEQDaKoVK8eJeB5ayZfm70IpVoV_ELrOaTdrG7ZTWqSLfjv3Votepph3ps3j3kInQAZAiH03JSrOKSEEsIKQnfQIYVCZUxxvvunP0DHMS4IISBYzkHtowPGgQiaF4eonZrwZpMt8fPDCD9gibN7m94_G1Na52PtLL607WaSau_w2LsUfBPx2DYNnphk8TQYF-tvtHb4pmuNw09NF-qlT9Yl_JJs-02PR2ivMk20xz91gF4nV9PxTXb3eH07Ht1lcwYiZYIyUQjFVSkZMMpNLmXFgQKT3K5nlMJ8litGbKWMmlV5oZgwwKWUqlIVG6CLje6ym7W2nPcugmn0MtStCZ_am1r_R1z9rt_8SitQioLsBc5-BIL_6GxMeuG74HrPmor-2RwgFz1ruGHNg48x2Gp7AYheJ6TXCeltQv3C6V9fW_pvHuwLhAKLwg</recordid><startdate>20210601</startdate><enddate>20210601</enddate><creator>Chen, Xuena</creator><creator>Zhao, Qingquan</creator><creator>Zhao, Yu-Li</creator><creator>Chai, Guo-Shi</creator><creator>Cheng, Weisheng</creator><creator>Zhao, Zhiju</creator><creator>Wang, Jia</creator><creator>Luo, Guan-Zheng</creator><creator>Cao, Nan</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</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>3V.</scope><scope>7XB</scope><scope>88I</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>M2O</scope><scope>M2P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1660-4728</orcidid></search><sort><creationdate>20210601</creationdate><title>Targeted RNA N 6 -Methyladenosine Demethylation Controls Cell Fate Transition in Human Pluripotent Stem Cells</title><author>Chen, Xuena ; Zhao, Qingquan ; Zhao, Yu-Li ; Chai, Guo-Shi ; Cheng, Weisheng ; Zhao, Zhiju ; Wang, Jia ; Luo, Guan-Zheng ; Cao, Nan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c315t-523595848d631324a766f4121364ed631221cb7830ef8a8bf79835a146668f8f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adenosine - analogs & derivatives</topic><topic>Adenosine - genetics</topic><topic>AlkB Homolog 5, RNA Demethylase - genetics</topic><topic>Caspases - genetics</topic><topic>Catalytic Domain - genetics</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Lineage - genetics</topic><topic>Cell Proliferation - genetics</topic><topic>Communication</topic><topic>Communications</topic><topic>CRISPR</topic><topic>Cytoplasm</topic><topic>Demethylation</topic><topic>Editors</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Embryonic Stem Cells - metabolism</topic><topic>Humans</topic><topic>Localization</topic><topic>Methylation</topic><topic>Methyltransferases - genetics</topic><topic>Mutation</topic><topic>Pluripotent Stem Cells - metabolism</topic><topic>Proteins</topic><topic>RNA Stability - genetics</topic><topic>RNA, Messenger - genetics</topic><topic>SOXB1 Transcription Factors - genetics</topic><topic>Stem cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Xuena</creatorcontrib><creatorcontrib>Zhao, Qingquan</creatorcontrib><creatorcontrib>Zhao, Yu-Li</creatorcontrib><creatorcontrib>Chai, Guo-Shi</creatorcontrib><creatorcontrib>Cheng, Weisheng</creatorcontrib><creatorcontrib>Zhao, Zhiju</creatorcontrib><creatorcontrib>Wang, Jia</creatorcontrib><creatorcontrib>Luo, Guan-Zheng</creatorcontrib><creatorcontrib>Cao, Nan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>Research Library</collection><collection>ProQuest Science Journals</collection><collection>Research Library (Corporate)</collection><collection>Access via ProQuest (Open Access)</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>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Advanced science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Xuena</au><au>Zhao, Qingquan</au><au>Zhao, Yu-Li</au><au>Chai, Guo-Shi</au><au>Cheng, Weisheng</au><au>Zhao, Zhiju</au><au>Wang, Jia</au><au>Luo, Guan-Zheng</au><au>Cao, Nan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeted RNA N 6 -Methyladenosine Demethylation Controls Cell Fate Transition in Human Pluripotent Stem Cells</atitle><jtitle>Advanced science</jtitle><addtitle>Adv Sci (Weinh)</addtitle><date>2021-06-01</date><risdate>2021</risdate><volume>8</volume><issue>11</issue><spage>e2003902</spage><pages>e2003902-</pages><issn>2198-3844</issn><eissn>2198-3844</eissn><abstract>Deficiency of the N
-methyladenosine (m
A) methyltransferase complex results in global reduction of m
A abundance and defective cell development in embryonic stem cells (ESCs). However, it's unclear whether regional m
A methylation affects cell fate decisions due to the inability to modulate individual m
A modification in ESCs with precise temporal control. Here, a targeted RNA m
A erasure (TRME) system is developed to achieve site-specific demethylation of RNAs in human ESCs (hESCs). TRME, in which a stably transfected, doxycycline-inducible dCas13a is fused to the catalytic domain of ALKBH5, can precisely and reversibly demethylate the targeted m
A site of mRNA and increase mRNA stability with limited off-target effects. It is further demonstrated that temporal m
A erasure on a single site of SOX2 is sufficient to control the differentiation of hESCs. This study provides a versatile toolbox to reveal the function of individual m
A modification in hESCs, enabling cell fate control studies at the epitranscriptional level.</abstract><cop>Germany</cop><pub>John Wiley & Sons, Inc</pub><pmid>34105279</pmid><doi>10.1002/advs.202003902</doi><orcidid>https://orcid.org/0000-0002-1660-4728</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2198-3844 |
| ispartof | Advanced science, 2021-06, Vol.8 (11), p.e2003902 |
| issn | 2198-3844 2198-3844 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8188216 |
| source | PubMed (Medline); MEDLINE; Wiley Online Library Journals; DOAJ Directory of Open Access Journals; Wiley Online Library (Open Access Collection); EZB Electronic Journals Library |
| subjects | Adenosine - analogs & derivatives Adenosine - genetics AlkB Homolog 5, RNA Demethylase - genetics Caspases - genetics Catalytic Domain - genetics Cell Differentiation - genetics Cell Lineage - genetics Cell Proliferation - genetics Communication Communications CRISPR Cytoplasm Demethylation Editors Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Humans Localization Methylation Methyltransferases - genetics Mutation Pluripotent Stem Cells - metabolism Proteins RNA Stability - genetics RNA, Messenger - genetics SOXB1 Transcription Factors - genetics Stem cells |
| title | Targeted RNA N 6 -Methyladenosine Demethylation Controls Cell Fate Transition 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=2024-12-17T15%3A44%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Targeted%20RNA%20N%206%20-Methyladenosine%20Demethylation%20Controls%20Cell%20Fate%20Transition%20in%20Human%20Pluripotent%20Stem%20Cells&rft.jtitle=Advanced%20science&rft.au=Chen,%20Xuena&rft.date=2021-06-01&rft.volume=8&rft.issue=11&rft.spage=e2003902&rft.pages=e2003902-&rft.issn=2198-3844&rft.eissn=2198-3844&rft_id=info:doi/10.1002/advs.202003902&rft_dat=%3Cproquest_pubme%3E2539041175%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2539041175&rft_id=info:pmid/34105279&rfr_iscdi=true |