Long noncoding RNAs are dynamically regulated during β-cell mass expansion in mouse pregnancy and control β-cell proliferation in vitro.
Pregnancy is associated with increased β-cell proliferation driven by prolactin. Long noncoding RNAs (lncRNA) are the most abundant RNA species in the mammalian genome, yet, their functional importance is mainly elusive.<h4>Aims/hypothesis</h4>This study tests the hypothesis that lncRNAs...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182371&type=printable |
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| author | Giorgia Sisino Alex-Xianghua Zhou Niklas Dahr Alan Sabirsh Mangala M Soundarapandian Ranjan Perera Erik Larsson-Lekholm Maria Chiara Magnone Magnus Althage Björn Tyrberg |
| author_facet | Giorgia Sisino Alex-Xianghua Zhou Niklas Dahr Alan Sabirsh Mangala M Soundarapandian Ranjan Perera Erik Larsson-Lekholm Maria Chiara Magnone Magnus Althage Björn Tyrberg |
| author_sort | Giorgia Sisino |
| collection | DOAJ |
| description | Pregnancy is associated with increased β-cell proliferation driven by prolactin. Long noncoding RNAs (lncRNA) are the most abundant RNA species in the mammalian genome, yet, their functional importance is mainly elusive.<h4>Aims/hypothesis</h4>This study tests the hypothesis that lncRNAs regulate β-cell proliferation in response to prolactin in the context of β-cell mass compensation in pregnancy.<h4>Methods</h4>The expression profile of lncRNAs in mouse islets at day 14.5 of pregnancy was explored by a bioinformatics approach, further confirmed by quantitative PCR at different days of pregnancy, and islet specificity was evaluated by comparing expression in islets versus other tissues. In order to establish the role of the candidate lncRNAs we studied cell proliferation in mouse islets and the MIN6 β-cell line by EdU incorporation and cell count.<h4>Results</h4>We found that a group of lncRNAs is differentially regulated in mouse islets at 14.5 days of pregnancy. At different stages of pregnancy, these lncRNAs are dynamically expressed, and expression is prolactin dependent in mouse islets and MIN6 cells. One of those lncRNAs, Gm16308 (Lnc03), is dynamically regulated during pregnancy, prolactin-dependent and islet-enriched. Silencing Lnc03 in primary β-cells and MIN6 cells inhibits, whereas over-expression stimulates, proliferation even in the absence of prolactin, demonstrating that Lnc03 regulates β-cell growth.<h4>Conclusions/interpretation</h4>During pregnancy mouse islet proliferation is correlated with dynamic changes of lncRNA expression. In particular, Lnc03 regulates mouse β-cell proliferation and may be a crucial component of β-cell proliferation in β-cell mass adaptation in both health and disease. |
| first_indexed | 2024-12-16T08:52:12Z |
| format | Article |
| id | doaj.art-89cc3161ca104650a8d09c3709f563a6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-14T14:09:36Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-89cc3161ca104650a8d09c3709f563a62025-02-27T05:37:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01128e018237110.1371/journal.pone.0182371Long noncoding RNAs are dynamically regulated during β-cell mass expansion in mouse pregnancy and control β-cell proliferation in vitro.Giorgia SisinoAlex-Xianghua ZhouNiklas DahrAlan SabirshMangala M SoundarapandianRanjan PereraErik Larsson-LekholmMaria Chiara MagnoneMagnus AlthageBjörn TyrbergPregnancy is associated with increased β-cell proliferation driven by prolactin. Long noncoding RNAs (lncRNA) are the most abundant RNA species in the mammalian genome, yet, their functional importance is mainly elusive.<h4>Aims/hypothesis</h4>This study tests the hypothesis that lncRNAs regulate β-cell proliferation in response to prolactin in the context of β-cell mass compensation in pregnancy.<h4>Methods</h4>The expression profile of lncRNAs in mouse islets at day 14.5 of pregnancy was explored by a bioinformatics approach, further confirmed by quantitative PCR at different days of pregnancy, and islet specificity was evaluated by comparing expression in islets versus other tissues. In order to establish the role of the candidate lncRNAs we studied cell proliferation in mouse islets and the MIN6 β-cell line by EdU incorporation and cell count.<h4>Results</h4>We found that a group of lncRNAs is differentially regulated in mouse islets at 14.5 days of pregnancy. At different stages of pregnancy, these lncRNAs are dynamically expressed, and expression is prolactin dependent in mouse islets and MIN6 cells. One of those lncRNAs, Gm16308 (Lnc03), is dynamically regulated during pregnancy, prolactin-dependent and islet-enriched. Silencing Lnc03 in primary β-cells and MIN6 cells inhibits, whereas over-expression stimulates, proliferation even in the absence of prolactin, demonstrating that Lnc03 regulates β-cell growth.<h4>Conclusions/interpretation</h4>During pregnancy mouse islet proliferation is correlated with dynamic changes of lncRNA expression. In particular, Lnc03 regulates mouse β-cell proliferation and may be a crucial component of β-cell proliferation in β-cell mass adaptation in both health and disease.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182371&type=printable |
| spellingShingle | Giorgia Sisino Alex-Xianghua Zhou Niklas Dahr Alan Sabirsh Mangala M Soundarapandian Ranjan Perera Erik Larsson-Lekholm Maria Chiara Magnone Magnus Althage Björn Tyrberg Long noncoding RNAs are dynamically regulated during β-cell mass expansion in mouse pregnancy and control β-cell proliferation in vitro. PLoS ONE |
| title | Long noncoding RNAs are dynamically regulated during β-cell mass expansion in mouse pregnancy and control β-cell proliferation in vitro. |
| title_full | Long noncoding RNAs are dynamically regulated during β-cell mass expansion in mouse pregnancy and control β-cell proliferation in vitro. |
| title_fullStr | Long noncoding RNAs are dynamically regulated during β-cell mass expansion in mouse pregnancy and control β-cell proliferation in vitro. |
| title_full_unstemmed | Long noncoding RNAs are dynamically regulated during β-cell mass expansion in mouse pregnancy and control β-cell proliferation in vitro. |
| title_short | Long noncoding RNAs are dynamically regulated during β-cell mass expansion in mouse pregnancy and control β-cell proliferation in vitro. |
| title_sort | long noncoding rnas are dynamically regulated during β cell mass expansion in mouse pregnancy and control β cell proliferation in vitro |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182371&type=printable |
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