Age- and pregnancy-associated DNA methylation changes in mammary epithelial cells.
Age- and pregnancy-associated DNA methylation changes in mammary epithelial cells.
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DOI：
10.1016/j.stemcr.2014.12.009
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发表时间：
2015-02-10
影响因子：
5.9
通讯作者：
Polyak, Kornelia
中科院分区：
文献类型：
--
作者：
Huh, Sung Jin;Clement, Kendell;Jee, David;Merlini, Alessandra;Choudhury, Sibgat;Maruyama, Reo;Yoo, Ronnie;Chytil, Anna;Boyle, Patrick;Ran, Fei Ann;Moses, Harold L.;Barcellos-Hoff, Mary Helen;Jackson-Grusby, Laurie;Meissner, Alexander;Polyak, Kornelia
产后乳腺发育和分化发生在青春期和妊娠期。为了探索DNA甲基化在这些过程中的作用，我们确定了CD24+CD61+CD29hi、CD24+CD61+CD29lo和CD24+CD61−CD29lo细胞群的全基因组DNA甲基化和基因表达谱，这些细胞群先前在不同年龄和生殖阶段与不同的生物学特性相关。我们发现妊娠对CD24+CD61+CD29hi和CD24+CD61+CD29lo细胞有最显著的影响，诱导了不同的表观遗传状态，并维持了一生。基因表达、DNA甲基化和组蛋白修饰谱的综合分析揭示了细胞类型和生殖阶段特异性的变化。基于p27和tgf - β信号的表达模式和乳腺外植体培养的结果，我们发现p27和tgf - β信号是CD24+CD61+CD29lo细胞增殖的关键调节因子。我们的研究结果表明，与妊娠对CD24+CD61+CD29hi和CD24+CD61+CD29lo细胞的影响相比，在腔内分化过程中DNA甲基化发生了相对较小的变化。妊娠诱导CD24+CD61+CD29hi细胞的DNA甲基化变化，在退休的育种者中，具有祖细胞特征的p27+细胞的频率较低，p27和TGFβ信号是CD24+CD61+CD29lo细胞的关键调节因子。Huh和他的同事们描述了来自不同年龄和生殖状态的小鼠的三种表型不同的乳腺上皮细胞群的整体基因表达和DNA甲基化谱。妊娠诱导了干细胞特征富集细胞DNA甲基化模式的持续变化，这可能影响自我更新和癌症风险。
Postnatal mammary gland development and differentiation occur during puberty and pregnancy. To explore the role of DNA methylation in these processes, we determined the genome-wide DNA methylation and gene expression profiles of CD24+CD61+CD29hi, CD24+CD61+CD29lo, and CD24+CD61−CD29lo cell populations that were previously associated with distinct biological properties at different ages and reproductive stages. We found that pregnancy had the most significant effects on CD24+CD61+CD29hi and CD24+CD61+CD29lo cells, inducing distinct epigenetic states that were maintained through life. Integrated analysis of gene expression, DNA methylation, and histone modification profiles revealed cell-type- and reproductive-stage-specific changes. We identified p27 and TGFβ signaling as key regulators of CD24+CD61+CD29lo cell proliferation, based on their expression patterns and results from mammary gland explant cultures. Our results suggest that relatively minor changes in DNA methylation occur during luminal differentiation compared with the effects of pregnancy on CD24+CD61+CD29hi and CD24+CD61+CD29lo cells. Molecular profile changes are cell-type, age, and reproductive-stage specific in mammary gland Pregnancy induces DNA methylation changes in CD24+CD61+CD29hi cells The frequency of p27+ cells with progenitor features is lower in retired breeders p27 and TGFβ signaling are key regulators of CD24+CD61+CD29lo cells In this work, Huh and colleagues characterized the global gene expression and DNA methylation profiles of three phenotypically distinct mammary epithelial cell populations from mice of different ages and reproductive states. Pregnancy induced persistent changes in the DNA methylation patterns of cells enriched for stem cell features that may impact self-renewal and cancer risk.
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影响因子：
4.5
作者：
Silver DL;Hou L;Somerville R;Young ME;Apte SS;Pavan WJ
通讯作者：
Pavan WJ
影响因子：
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作者：
Choudhury, Sibgat;Almendro, Vanessa;Polyak, Kornelia
通讯作者：
Polyak, Kornelia
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通讯作者：
Jaenisch, R
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通讯作者：
Wahl GM