LINE-1 transcription activates long-range gene expression
Long interspersed nuclear element-1 (LINE-1 or L1) is a retrotransposon group that constitutes 17% of the human genome and shows variable expression across cell types. However, the control of L1 expression and its function in gene regulation are incompletely understood. Here we show that L1 transcri...
Gespeichert in:
| Veröffentlicht in: | Nature genetics 2024-07, Vol.56 (7), p.1494-1502 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1502 |
|---|---|
| container_issue | 7 |
| container_start_page | 1494 |
| container_title | Nature genetics |
| container_volume | 56 |
| creator | Li, Xiufeng Bie, Luyao Wang, Yang Hong, Yaqiang Zhou, Ziqiang Fan, Yiming Yan, Xiaohan Tao, Yibing Huang, Chunyi Zhang, Yongyan Sun, Xueyan Li, John Xiao He Zhang, Jing Chang, Zai Xi, Qiaoran Meng, Anming Shen, Xiaohua Xie, Wei Liu, Nian |
| description | Long interspersed nuclear element-1 (LINE-1 or L1) is a retrotransposon group that constitutes 17% of the human genome and shows variable expression across cell types. However, the control of L1 expression and its function in gene regulation are incompletely understood. Here we show that L1 transcription activates long-range gene expression. Genome-wide CRISPR–Cas9 screening using a reporter driven by the L1 5′ UTR in human cells identifies functionally diverse genes affecting L1 expression. Unexpectedly, altering L1 expression by knockout of regulatory genes impacts distant gene expression. L1s can physically contact their distal target genes, with these interactions becoming stronger upon L1 activation and weaker when L1 is silenced. Remarkably, L1s contact and activate genes essential for zygotic genome activation (ZGA), and L1 knockdown impairs ZGA, leading to developmental arrest in mouse embryos. These results characterize the regulation and function of L1 in long-range gene activation and reveal its importance in mammalian ZGA.
A CRISPR–Cas9 screen identifies genes that modulate long interspersed nuclear element-1 (LINE-1) expression in human cells. LINE-1 5′ UTRs have enhancer features and can activate long-range gene expression, including during zygotic genome activation. |
| doi_str_mv | 10.1038/s41588-024-01789-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3065983256</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3065983256</sourcerecordid><originalsourceid>FETCH-LOGICAL-c305t-c949f09f76a3bc361fa5579610a8e56f5b2fa01151703b597b5c6930f85cb9153</originalsourceid><addsrcrecordid>eNp9kE1LAzEQhoMotlb_gAdZ8OIlOrP52OQopX5A0YueQzZmy5Z2tya7ov_e1K0KHjzNwDzzzvAQcopwicDUVeQolKKQcwpYKE3FHhmj4JJigWo_9SCRcmByRI5iXAIg56AOyYgpxbVENiZ6fv8wo5h1wTbRhXrT1W2TWdfVb7bzMVu1zYKm2cJnC9_4zL9vgo8xQcfkoLKr6E92dUKeb2ZP0zs6f7y9n17PqWMgOuo01xXoqpCWlY5JrKwQRToOVnkhK1HmlQVEgQWwUuiiFE5qBpUSrtQo2IRcDLmb0L72PnZmXUfnVyvb-LaPhoEUWrFcyISe_0GXbR-a9F2ilOSIAJCofKBcaGMMvjKbUK9t-DAIZivWDGJNEmu-xJrtF2e76L5c-5eflW-TCWADENMo6Qq_t_-J_QSr2oDp</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3086411000</pqid></control><display><type>article</type><title>LINE-1 transcription activates long-range gene expression</title><source>Nature</source><source>SpringerLink (Online service)</source><creator>Li, Xiufeng ; Bie, Luyao ; Wang, Yang ; Hong, Yaqiang ; Zhou, Ziqiang ; Fan, Yiming ; Yan, Xiaohan ; Tao, Yibing ; Huang, Chunyi ; Zhang, Yongyan ; Sun, Xueyan ; Li, John Xiao He ; Zhang, Jing ; Chang, Zai ; Xi, Qiaoran ; Meng, Anming ; Shen, Xiaohua ; Xie, Wei ; Liu, Nian</creator><creatorcontrib>Li, Xiufeng ; Bie, Luyao ; Wang, Yang ; Hong, Yaqiang ; Zhou, Ziqiang ; Fan, Yiming ; Yan, Xiaohan ; Tao, Yibing ; Huang, Chunyi ; Zhang, Yongyan ; Sun, Xueyan ; Li, John Xiao He ; Zhang, Jing ; Chang, Zai ; Xi, Qiaoran ; Meng, Anming ; Shen, Xiaohua ; Xie, Wei ; Liu, Nian</creatorcontrib><description>Long interspersed nuclear element-1 (LINE-1 or L1) is a retrotransposon group that constitutes 17% of the human genome and shows variable expression across cell types. However, the control of L1 expression and its function in gene regulation are incompletely understood. Here we show that L1 transcription activates long-range gene expression. Genome-wide CRISPR–Cas9 screening using a reporter driven by the L1 5′ UTR in human cells identifies functionally diverse genes affecting L1 expression. Unexpectedly, altering L1 expression by knockout of regulatory genes impacts distant gene expression. L1s can physically contact their distal target genes, with these interactions becoming stronger upon L1 activation and weaker when L1 is silenced. Remarkably, L1s contact and activate genes essential for zygotic genome activation (ZGA), and L1 knockdown impairs ZGA, leading to developmental arrest in mouse embryos. These results characterize the regulation and function of L1 in long-range gene activation and reveal its importance in mammalian ZGA.
A CRISPR–Cas9 screen identifies genes that modulate long interspersed nuclear element-1 (LINE-1) expression in human cells. LINE-1 5′ UTRs have enhancer features and can activate long-range gene expression, including during zygotic genome activation.</description><identifier>ISSN: 1061-4036</identifier><identifier>ISSN: 1546-1718</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/s41588-024-01789-5</identifier><identifier>PMID: 38849613</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>13/1 ; 13/100 ; 13/109 ; 14/63 ; 38/22 ; 38/23 ; 38/39 ; 38/47 ; 38/77 ; 38/91 ; 631/114/2163 ; 631/136/2086 ; 631/208/191 ; 631/208/212 ; 64/60 ; 82/80 ; Agriculture ; Animal Genetics and Genomics ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; CRISPR ; Embryos ; Gene expression ; Gene Function ; Gene regulation ; Gene silencing ; Genes ; Genomes ; Human Genetics ; Long interspersed nucleotide elements ; Proteins ; Transcription activation</subject><ispartof>Nature genetics, 2024-07, Vol.56 (7), p.1494-1502</ispartof><rights>The Author(s), under exclusive licence to Springer Nature America, Inc. 2024. corrected publication 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer Nature America, Inc.</rights><rights>Copyright Nature Publishing Group Jul 2024</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c305t-c949f09f76a3bc361fa5579610a8e56f5b2fa01151703b597b5c6930f85cb9153</citedby><cites>FETCH-LOGICAL-c305t-c949f09f76a3bc361fa5579610a8e56f5b2fa01151703b597b5c6930f85cb9153</cites><orcidid>0000-0002-7496-4131 ; 0000-0003-2126-3849 ; 0000-0002-4721-9662 ; 0000-0002-4590-1502 ; 0000-0002-3545-4278 ; 0000-0001-7246-7732 ; 0000-0001-7228-3431</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41588-024-01789-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41588-024-01789-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38849613$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Xiufeng</creatorcontrib><creatorcontrib>Bie, Luyao</creatorcontrib><creatorcontrib>Wang, Yang</creatorcontrib><creatorcontrib>Hong, Yaqiang</creatorcontrib><creatorcontrib>Zhou, Ziqiang</creatorcontrib><creatorcontrib>Fan, Yiming</creatorcontrib><creatorcontrib>Yan, Xiaohan</creatorcontrib><creatorcontrib>Tao, Yibing</creatorcontrib><creatorcontrib>Huang, Chunyi</creatorcontrib><creatorcontrib>Zhang, Yongyan</creatorcontrib><creatorcontrib>Sun, Xueyan</creatorcontrib><creatorcontrib>Li, John Xiao He</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Chang, Zai</creatorcontrib><creatorcontrib>Xi, Qiaoran</creatorcontrib><creatorcontrib>Meng, Anming</creatorcontrib><creatorcontrib>Shen, Xiaohua</creatorcontrib><creatorcontrib>Xie, Wei</creatorcontrib><creatorcontrib>Liu, Nian</creatorcontrib><title>LINE-1 transcription activates long-range gene expression</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Long interspersed nuclear element-1 (LINE-1 or L1) is a retrotransposon group that constitutes 17% of the human genome and shows variable expression across cell types. However, the control of L1 expression and its function in gene regulation are incompletely understood. Here we show that L1 transcription activates long-range gene expression. Genome-wide CRISPR–Cas9 screening using a reporter driven by the L1 5′ UTR in human cells identifies functionally diverse genes affecting L1 expression. Unexpectedly, altering L1 expression by knockout of regulatory genes impacts distant gene expression. L1s can physically contact their distal target genes, with these interactions becoming stronger upon L1 activation and weaker when L1 is silenced. Remarkably, L1s contact and activate genes essential for zygotic genome activation (ZGA), and L1 knockdown impairs ZGA, leading to developmental arrest in mouse embryos. These results characterize the regulation and function of L1 in long-range gene activation and reveal its importance in mammalian ZGA.
A CRISPR–Cas9 screen identifies genes that modulate long interspersed nuclear element-1 (LINE-1) expression in human cells. LINE-1 5′ UTRs have enhancer features and can activate long-range gene expression, including during zygotic genome activation.</description><subject>13/1</subject><subject>13/100</subject><subject>13/109</subject><subject>14/63</subject><subject>38/22</subject><subject>38/23</subject><subject>38/39</subject><subject>38/47</subject><subject>38/77</subject><subject>38/91</subject><subject>631/114/2163</subject><subject>631/136/2086</subject><subject>631/208/191</subject><subject>631/208/212</subject><subject>64/60</subject><subject>82/80</subject><subject>Agriculture</subject><subject>Animal Genetics and Genomics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>CRISPR</subject><subject>Embryos</subject><subject>Gene expression</subject><subject>Gene Function</subject><subject>Gene regulation</subject><subject>Gene silencing</subject><subject>Genes</subject><subject>Genomes</subject><subject>Human Genetics</subject><subject>Long interspersed nucleotide elements</subject><subject>Proteins</subject><subject>Transcription activation</subject><issn>1061-4036</issn><issn>1546-1718</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kE1LAzEQhoMotlb_gAdZ8OIlOrP52OQopX5A0YueQzZmy5Z2tya7ov_e1K0KHjzNwDzzzvAQcopwicDUVeQolKKQcwpYKE3FHhmj4JJigWo_9SCRcmByRI5iXAIg56AOyYgpxbVENiZ6fv8wo5h1wTbRhXrT1W2TWdfVb7bzMVu1zYKm2cJnC9_4zL9vgo8xQcfkoLKr6E92dUKeb2ZP0zs6f7y9n17PqWMgOuo01xXoqpCWlY5JrKwQRToOVnkhK1HmlQVEgQWwUuiiFE5qBpUSrtQo2IRcDLmb0L72PnZmXUfnVyvb-LaPhoEUWrFcyISe_0GXbR-a9F2ilOSIAJCofKBcaGMMvjKbUK9t-DAIZivWDGJNEmu-xJrtF2e76L5c-5eflW-TCWADENMo6Qq_t_-J_QSr2oDp</recordid><startdate>20240701</startdate><enddate>20240701</enddate><creator>Li, Xiufeng</creator><creator>Bie, Luyao</creator><creator>Wang, Yang</creator><creator>Hong, Yaqiang</creator><creator>Zhou, Ziqiang</creator><creator>Fan, Yiming</creator><creator>Yan, Xiaohan</creator><creator>Tao, Yibing</creator><creator>Huang, Chunyi</creator><creator>Zhang, Yongyan</creator><creator>Sun, Xueyan</creator><creator>Li, John Xiao He</creator><creator>Zhang, Jing</creator><creator>Chang, Zai</creator><creator>Xi, Qiaoran</creator><creator>Meng, Anming</creator><creator>Shen, Xiaohua</creator><creator>Xie, Wei</creator><creator>Liu, Nian</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7496-4131</orcidid><orcidid>https://orcid.org/0000-0003-2126-3849</orcidid><orcidid>https://orcid.org/0000-0002-4721-9662</orcidid><orcidid>https://orcid.org/0000-0002-4590-1502</orcidid><orcidid>https://orcid.org/0000-0002-3545-4278</orcidid><orcidid>https://orcid.org/0000-0001-7246-7732</orcidid><orcidid>https://orcid.org/0000-0001-7228-3431</orcidid></search><sort><creationdate>20240701</creationdate><title>LINE-1 transcription activates long-range gene expression</title><author>Li, Xiufeng ; Bie, Luyao ; Wang, Yang ; Hong, Yaqiang ; Zhou, Ziqiang ; Fan, Yiming ; Yan, Xiaohan ; Tao, Yibing ; Huang, Chunyi ; Zhang, Yongyan ; Sun, Xueyan ; Li, John Xiao He ; Zhang, Jing ; Chang, Zai ; Xi, Qiaoran ; Meng, Anming ; Shen, Xiaohua ; Xie, Wei ; Liu, Nian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c305t-c949f09f76a3bc361fa5579610a8e56f5b2fa01151703b597b5c6930f85cb9153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>13/1</topic><topic>13/100</topic><topic>13/109</topic><topic>14/63</topic><topic>38/22</topic><topic>38/23</topic><topic>38/39</topic><topic>38/47</topic><topic>38/77</topic><topic>38/91</topic><topic>631/114/2163</topic><topic>631/136/2086</topic><topic>631/208/191</topic><topic>631/208/212</topic><topic>64/60</topic><topic>82/80</topic><topic>Agriculture</topic><topic>Animal Genetics and Genomics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>CRISPR</topic><topic>Embryos</topic><topic>Gene expression</topic><topic>Gene Function</topic><topic>Gene regulation</topic><topic>Gene silencing</topic><topic>Genes</topic><topic>Genomes</topic><topic>Human Genetics</topic><topic>Long interspersed nucleotide elements</topic><topic>Proteins</topic><topic>Transcription activation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Xiufeng</creatorcontrib><creatorcontrib>Bie, Luyao</creatorcontrib><creatorcontrib>Wang, Yang</creatorcontrib><creatorcontrib>Hong, Yaqiang</creatorcontrib><creatorcontrib>Zhou, Ziqiang</creatorcontrib><creatorcontrib>Fan, Yiming</creatorcontrib><creatorcontrib>Yan, Xiaohan</creatorcontrib><creatorcontrib>Tao, Yibing</creatorcontrib><creatorcontrib>Huang, Chunyi</creatorcontrib><creatorcontrib>Zhang, Yongyan</creatorcontrib><creatorcontrib>Sun, Xueyan</creatorcontrib><creatorcontrib>Li, John Xiao He</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Chang, Zai</creatorcontrib><creatorcontrib>Xi, Qiaoran</creatorcontrib><creatorcontrib>Meng, Anming</creatorcontrib><creatorcontrib>Shen, Xiaohua</creatorcontrib><creatorcontrib>Xie, Wei</creatorcontrib><creatorcontrib>Liu, Nian</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Xiufeng</au><au>Bie, Luyao</au><au>Wang, Yang</au><au>Hong, Yaqiang</au><au>Zhou, Ziqiang</au><au>Fan, Yiming</au><au>Yan, Xiaohan</au><au>Tao, Yibing</au><au>Huang, Chunyi</au><au>Zhang, Yongyan</au><au>Sun, Xueyan</au><au>Li, John Xiao He</au><au>Zhang, Jing</au><au>Chang, Zai</au><au>Xi, Qiaoran</au><au>Meng, Anming</au><au>Shen, Xiaohua</au><au>Xie, Wei</au><au>Liu, Nian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>LINE-1 transcription activates long-range gene expression</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>2024-07-01</date><risdate>2024</risdate><volume>56</volume><issue>7</issue><spage>1494</spage><epage>1502</epage><pages>1494-1502</pages><issn>1061-4036</issn><issn>1546-1718</issn><eissn>1546-1718</eissn><abstract>Long interspersed nuclear element-1 (LINE-1 or L1) is a retrotransposon group that constitutes 17% of the human genome and shows variable expression across cell types. However, the control of L1 expression and its function in gene regulation are incompletely understood. Here we show that L1 transcription activates long-range gene expression. Genome-wide CRISPR–Cas9 screening using a reporter driven by the L1 5′ UTR in human cells identifies functionally diverse genes affecting L1 expression. Unexpectedly, altering L1 expression by knockout of regulatory genes impacts distant gene expression. L1s can physically contact their distal target genes, with these interactions becoming stronger upon L1 activation and weaker when L1 is silenced. Remarkably, L1s contact and activate genes essential for zygotic genome activation (ZGA), and L1 knockdown impairs ZGA, leading to developmental arrest in mouse embryos. These results characterize the regulation and function of L1 in long-range gene activation and reveal its importance in mammalian ZGA.
A CRISPR–Cas9 screen identifies genes that modulate long interspersed nuclear element-1 (LINE-1) expression in human cells. LINE-1 5′ UTRs have enhancer features and can activate long-range gene expression, including during zygotic genome activation.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>38849613</pmid><doi>10.1038/s41588-024-01789-5</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-7496-4131</orcidid><orcidid>https://orcid.org/0000-0003-2126-3849</orcidid><orcidid>https://orcid.org/0000-0002-4721-9662</orcidid><orcidid>https://orcid.org/0000-0002-4590-1502</orcidid><orcidid>https://orcid.org/0000-0002-3545-4278</orcidid><orcidid>https://orcid.org/0000-0001-7246-7732</orcidid><orcidid>https://orcid.org/0000-0001-7228-3431</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 2024-07, Vol.56 (7), p.1494-1502 |
| issn | 1061-4036 1546-1718 1546-1718 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_3065983256 |
| source | Nature; SpringerLink (Online service) |
| subjects | 13/1 13/100 13/109 14/63 38/22 38/23 38/39 38/47 38/77 38/91 631/114/2163 631/136/2086 631/208/191 631/208/212 64/60 82/80 Agriculture Animal Genetics and Genomics Biomedical and Life Sciences Biomedicine Cancer Research CRISPR Embryos Gene expression Gene Function Gene regulation Gene silencing Genes Genomes Human Genetics Long interspersed nucleotide elements Proteins Transcription activation |
| title | LINE-1 transcription activates long-range gene expression |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T05%3A58%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=LINE-1%20transcription%20activates%20long-range%20gene%20expression&rft.jtitle=Nature%20genetics&rft.au=Li,%20Xiufeng&rft.date=2024-07-01&rft.volume=56&rft.issue=7&rft.spage=1494&rft.epage=1502&rft.pages=1494-1502&rft.issn=1061-4036&rft.eissn=1546-1718&rft_id=info:doi/10.1038/s41588-024-01789-5&rft_dat=%3Cproquest_cross%3E3065983256%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3086411000&rft_id=info:pmid/38849613&rfr_iscdi=true |