Alzheimer's disease-related transcriptional sex differences in myeloid cells.
Alzheimer's disease-related transcriptional sex differences in myeloid cells.
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DOI：
10.1186/s12974-022-02604-w
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发表时间：
2022-10-05
影响因子：
9.3
通讯作者：
中科院分区：
文献类型：
--
作者：
在许多与免疫反应失调有关的疾病中已经发现了性别差异，包括阿尔茨海默病（AD），其中约三分之二的患者是女性。越来越多的研究表明，小胶质细胞可能在这种疾病的发病机制中发挥因果作用。我们假设人类髓系细胞转录组的性别差异可能导致AD患病率的性别差异。为了探索这一点，我们评估了从四种人源性骨髓细胞群体产生的批量和单核RNA测序数据集：死后小胶质细胞核、外周单核细胞、单核细胞源性巨噬细胞（MDM）和诱导多能干细胞源性小胶质细胞样细胞（MGL）。我们发现AD风险基因的表达，与AD炎症反应相关的基因特征，以及与促炎免疫反应相关的基因在从没有生前神经系统疾病的老年女性供体中分离的小胶质细胞核中富集，相对于男性。此外，发现这些炎症相关基因集富集在从绝经后妇女分离的外周血单核细胞和从绝经前个体相对于年龄匹配的男性获得的MDM中。这些基因集的表达在来自月经周期中血液采样的女性的MDM中或在与17 β-雌二醇培养的MGL中没有差异。这表明，在女性骨髓细胞中观察到的基因集富集不是由急性激素影响驱动的。总之，这些数据支持了这样的假设，即AD在女性中的患病率增加可能部分地由骨髓细胞表型偏向于与AD相关的生物过程的表达来解释。在线版本包含补充材料，可通过10.1186/s12974 - 022 - 02604-w获得。
Sex differences have been identified in many diseases associated with dysregulated immune responses, including Alzheimer’s disease (AD), for which approximately two-thirds of patients are women. An accumulating body of research indicates that microglia may play a causal role in the pathogenesis of this disease. We hypothesised that sex differences in the transcriptome of human myeloid cells may contribute to the sex difference observed in AD prevalence. To explore this, we assessed bulk and single-nuclear RNA sequencing data sets generated from four human derived myeloid cell populations: post-mortem microglial nuclei, peripheral monocytes, monocyte-derived macrophages (MDMs) and induced pluripotent stem cell derived microglial-like cells (MGLs). We found that expression of AD risk genes, gene signatures associated with the inflammatory response in AD, and genes related to proinflammatory immune responses were enriched in microglial nuclei isolated from aged female donors without ante-mortem neurological disease, relative to those from males. In addition, these inflammation-associated gene sets were found to be enriched in peripheral monocytes isolated from postmenopausal women and in MDMs obtained from premenopausal individuals relative to age-matched males. Expression of these gene sets did not differ in MDMs derived from women whose blood was sampled across the menstrual cycle or in MGLs cultured with 17β-oestradiol. This suggests that the observed gene set enrichments in myeloid cells from women were not being driven by acute hormonal influences. Together, these data support the hypothesis that the increased prevalence of AD in women may be partly explained by a myeloid cell phenotype biased towards expression of biological processes relevant to AD. The online version contains supplementary material available at 10.1186/s12974-022-02604-w.
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影响因子：
48
作者：
Huber W;Carey VJ;Gentleman R;Anders S;Carlson M;Carvalho BS;Bravo HC;Davis S;Gatto L;Girke T;Gottardo R;Hahne F;Hansen KD;Irizarry RA;Lawrence M;Love MI;MacDonald J;Obenchain V;Oleś AK;Pagès H;Reyes A;Shannon P;Smyth GK;Tenenbaum D;Waldron L;Morgan M
通讯作者：
Morgan M
DOI：
10.1038/s41531-021-00180-z
发表时间：
2021-04-13
期刊：
NPJ Parkinson's disease
影响因子：
--
作者：
Carlisle SM;Qin H;Hendrickson RC;Muwanguzi JE;Lefkowitz EJ;Kennedy RE;Yan Z;Yacoubian TA;Benveniste EN;West AB;Harms AS;Standaert DG
通讯作者：
Standaert DG
DOI：
10.1038/nri2394
发表时间：
2008-09
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Fish EN
通讯作者：
Fish EN
影响因子：
4.2
作者：
Balogun, M. A.;Vyse, A. J.;Ramsay, M. E.
通讯作者：
Ramsay, M. E.
影响因子：
8.8
作者：
Guneykaya, Dilansu;Ivanov, Andranik;Wolf, Susanne A.
通讯作者：
Wolf, Susanne A.