Long noncoding RNAs are dynamically regulated during β-cell mass expansion in mouse pregnancy and control β-cell proliferation in vitro.
Long noncoding RNAs are dynamically regulated during β-cell mass expansion in mouse pregnancy and control β-cell proliferation in vitro.
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DOI：
10.1371/journal.pone.0182371
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Tyrberg B
中科院分区：
文献类型：
--
作者：
Sisino G;Zhou AX;Dahr N;Sabirsh A;Soundarapandian MM;Perera R;Larsson-Lekholm E;Magnone MC;Althage M;Tyrberg B
妊娠与催乳素驱动的β细胞增殖增加相关。长链非编码RNA（lncRNA）是哺乳动物基因组中最丰富的RNA种类，然而，其功能的重要性主要是难以捉摸的。目的/假设：本研究验证了以下假设：在妊娠期β细胞质量补偿的背景下，lncRNA调节β细胞增殖以响应催乳素。研究方法：通过生物信息学方法研究了妊娠第14.5天小鼠胰岛中lncRNA的表达谱，并在妊娠不同天数通过定量PCR进一步证实，通过比较胰岛与其他组织中的表达来评估胰岛特异性。为了确定候选lncRNA的作用，我们通过EdU掺入和细胞计数研究了小鼠胰岛和MIN 6 β细胞系中的细胞增殖。结果：我们发现一组lncRNA在妊娠14.5天的小鼠胰岛中差异调节。在妊娠的不同阶段，这些lncRNA动态表达，并且在小鼠胰岛和MIN 6细胞中表达是催乳素依赖性的。其中一种lncRNA，Gm 16308（Lnc 03），在妊娠期间动态调节，催乳素依赖性和胰岛富集。在原代β-细胞和MIN 6细胞中沉默Lnc 03抑制增殖，而过表达刺激增殖，即使在没有催乳素的情况下也是如此，这表明Lnc 03调节β-细胞生长。结论/解释：妊娠期间小鼠胰岛增殖与lncRNA表达的动态变化相关。特别地，Lnc 03调节小鼠β细胞增殖，并且可能是健康和疾病中β细胞质量适应中β细胞增殖的关键组分。
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. Aims/hypothesis: 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. Methods: 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. Results: 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. Conclusions/interpretation: 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.
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影响因子：
56.9
作者：
Kapranov, Philipp;Cheng, Jill;Gingeras, Thomas R.
通讯作者：
Gingeras, Thomas R.
影响因子：
7.7
作者：
Stewart AF;Hussain MA;García-Ocaña A;Vasavada RC;Bhushan A;Bernal-Mizrachi E;Kulkarni RN
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Kulkarni RN
DOI：
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发表时间：
2010-09
期刊：
Reproduction (Cambridge, England)
影响因子：
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通讯作者：
Catalano PM
影响因子：
7.7
作者：
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通讯作者：
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12.3
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