Unusual X chromosome inactivation maintenance in female alveolar type 2 cells is correlated with increased numbers of X-linked escape genes and sex-biased gene expression.
Unusual X chromosome inactivation maintenance in female alveolar type 2 cells is correlated with increased numbers of X-linked escape genes and sex-biased gene expression.
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DOI：
10.1016/j.stemcr.2022.12.005
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发表时间：
2023-02-14
影响因子：
5.9
通讯作者：
Anguera, Montserrat C.
中科院分区：
文献类型：
--
作者：
Sierra, Isabel;Pyfrom, Sarah;Weiner, Aaron;Zhao, Gan;Driscoll, Amanda;Yu, Xiang;Gregory, Brian D.;Vaughan, Andrew E.;Anguera, Montserrat C.
性别差异存在于许多肺部病变，包括COVID-19和肺纤维化，但其机制基础尚不清楚。肺泡2型细胞（AT2s）在肺泡肺再生中发挥关键作用，其表达的X连锁Ace2基因在肺修复和SARS-CoV-2发病机制中发挥作用，这表明AT2s中的X染色体失活（XCI）可能影响性别偏见的肺病理。在这里，我们研究了雄性和雌性AT2s的XCI维持和性别特异性基因表达谱。值得注意的是，在人类和小鼠的AT2s中，失活的X染色体（Xi）缺乏健壮的规范Xist RNA“云”和较少富集的异色修饰。我们证明，小鼠AT2s中约68%的表达x连锁基因，包括Ace2，可以逃避XCI。男性和女性AT2s在全基因组表达上存在差异，可能会影响肺部生理和病理生理反应。这些研究支持重新关注at2作为肺部疾病性别差异的潜在因素。小鼠肺泡2型细胞缺乏Xist RNA“云”和较少的异色标记富集，在小鼠AT2s中68%的表达X相关基因，包括Ace2，逃避XCI。AT2s全基因组性别特异性基因表达谱差异Anguera， Vaughan和同事表明，肺泡2型（AT2s）细胞维持X染色体失活，在失活的X上较少的表观遗传修饰。大量的x连锁基因“逃脱”了转录沉默。AT2细胞也表现出显著的全基因组性别偏倚基因表达，这可能影响肺生理和病理生理反应。
Sex differences exist for many lung pathologies, including COVID-19 and pulmonary fibrosis, but the mechanistic basis for this remains unclear. Alveolar type 2 cells (AT2s), which play a key role in alveolar lung regeneration, express the X-linked Ace2 gene that has roles in lung repair and SARS-CoV-2 pathogenesis, suggesting that X chromosome inactivation (XCI) in AT2s might impact sex-biased lung pathology. Here we investigate XCI maintenance and sex-specific gene expression profiles using male and female AT2s. Remarkably, the inactive X chromosome (Xi) lacks robust canonical Xist RNA “clouds” and less enrichment of heterochromatic modifications in human and mouse AT2s. We demonstrate that about 68% of expressed X-linked genes in mouse AT2s, including Ace2, escape XCI. There are genome-wide expression differences between male and female AT2s, likely influencing both lung physiology and pathophysiologic responses. These studies support a renewed focus on AT2s as a potential contributor to sex-biased differences in lung disease. XCI maintenance and sex-specific gene expression profiles of alveolar type 2 cells The Xi lacks Xist RNA “clouds” and less heterochromatic mark enrichment 68% of expressed X-linked genes in mouse AT2s, including Ace2, escape XCI Genome-wide sex-specific gene expression profile differences in AT2s Anguera, Vaughan, and colleagues show that lung alveolar type 2 (AT2s) cells maintain X chromosome inactivation with fewer epigenetic modifications on the inactive X, with very high numbers of X-linked genes that “escape” transcriptional silencing. AT2 cells also exhibit significant genome-wide sex-biased gene expression, which likely influences lung physiology and pathophysiologic responses.
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DOI：
10.1097/ta.0b013e31822c0d31
发表时间：
2011-10-01
影响因子：
--
作者：
Heffernan, Daithi S.;Dossett, Lesly A.;May, Addison K.
通讯作者：
May, Addison K.
影响因子：
3.6
作者：
McCoy, DM;Salome, RG;Mallampalli, RK
通讯作者：
Mallampalli, RK
影响因子：
23.9
作者：
Katsura H;Sontake V;Tata A;Kobayashi Y;Edwards CE;Heaton BE;Konkimalla A;Asakura T;Mikami Y;Fritch EJ;Lee PJ;Heaton NS;Boucher RC;Randell SH;Baric RS;Tata PR
通讯作者：
Tata PR
DOI：
10.4049/jimmunol.1601896
发表时间：
2017-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Channappanavar R;Fett C;Mack M;Ten Eyck PP;Meyerholz DK;Perlman S
通讯作者：
Perlman S
影响因子：
64.8
作者：
Imai Y;Kuba K;Rao S;Huan Y;Guo F;Guan B;Yang P;Sarao R;Wada T;Leong-Poi H;Crackower MA;Fukamizu A;Hui CC;Hein L;Uhlig S;Slutsky AS;Jiang C;Penninger JM
通讯作者：
Penninger JM