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Abstract：
At present, there is no clear understanding of the effect of long-duration spaceflight on the major enzymes that govern the metabolism of omega-6 and omega-3 fatty acids. To address this gap in knowledge, we used data from the NASA Twins Study, which includes a multiscale omics investigation of the changes that occurred during a year-long (340 days) human spaceflight. Embedded within the NASA Twins data are specific analytes associated with fatty acid metabolism.
To examine the long-chain fatty acid desaturases and elongases in a single human during 1 year in space.
One male twin was on board the International Space Station (ISS) for 1 year, while his monozygotic twin served as a genetically matched ground control. Longitudinal assessments included the genome, epige-nome, transcriptome, proteome, metabolome, microbiome, and immunome during the mission, as well as 6 months before and after. The gene-specific fatty acid desaturase and elongase transcriptome data (FADS1, FADS2, ELOVL2, and ELOVL5) were extracted from untargeted RNA-seq measurements derived from white blood cell fractions.
Most data from the elongases and desaturases exhibited relatively similar expression profiles (R2 >0.6) over time for the CD8, CD19, and lymphocyte-depleted (LD) cell fractions, indicating overall conservation of function within and between the subjects. Both cell-type and temporal specificity was observed in some cases, and some differences were also apparent between the polyadenylated (polyA) fraction of processed RNAs versus the ribodepleted (ribo-) fraction. The flight subject showed a stronger enrichment of the fatty acid metabolic process pathway across almost all cell types (columns, CD4, CD8, CPT, and LD), most especially in the ribodepleted fraction of RNA, but also with the polyA+ fraction of RNA. Gene set enrichment analysis (GSEA) measures across three related fatty acid metabolism pathways showed a differential between the ground and the flight subject.
There appears to be no persistent alteration of desaturase and elongase gene expression associated with 1 year in space. However, these data provide evidence that cellular lipid metabolism can be responsive and dynamic to spaceflight, even though it appears cell-type and context specific, most notably in terms of the fraction of RNA measured and the collection protocols. These results also provide new evidence of mid-flight spikes in expression of selected genes, which may indicate transient responses to specific insults during spaceflight.
To examine the long-chain fatty acid desaturases and elongases in a single human during 1 year in space.
One male twin was on board the International Space Station (ISS) for 1 year, while his monozygotic twin served as a genetically matched ground control. Longitudinal assessments included the genome, epige-nome, transcriptome, proteome, metabolome, microbiome, and immunome during the mission, as well as 6 months before and after. The gene-specific fatty acid desaturase and elongase transcriptome data (FADS1, FADS2, ELOVL2, and ELOVL5) were extracted from untargeted RNA-seq measurements derived from white blood cell fractions.
Most data from the elongases and desaturases exhibited relatively similar expression profiles (R2 >0.6) over time for the CD8, CD19, and lymphocyte-depleted (LD) cell fractions, indicating overall conservation of function within and between the subjects. Both cell-type and temporal specificity was observed in some cases, and some differences were also apparent between the polyadenylated (polyA) fraction of processed RNAs versus the ribodepleted (ribo-) fraction. The flight subject showed a stronger enrichment of the fatty acid metabolic process pathway across almost all cell types (columns, CD4, CD8, CPT, and LD), most especially in the ribodepleted fraction of RNA, but also with the polyA+ fraction of RNA. Gene set enrichment analysis (GSEA) measures across three related fatty acid metabolism pathways showed a differential between the ground and the flight subject.
There appears to be no persistent alteration of desaturase and elongase gene expression associated with 1 year in space. However, these data provide evidence that cellular lipid metabolism can be responsive and dynamic to spaceflight, even though it appears cell-type and context specific, most notably in terms of the fraction of RNA measured and the collection protocols. These results also provide new evidence of mid-flight spikes in expression of selected genes, which may indicate transient responses to specific insults during spaceflight.
摘要：
目前,对于长期太空飞行对控制omega-6和omega-3脂肪酸代谢的主要酶的影响尚不清楚。为了解决这个知识差距，我们使用了NASA双胞胎研究的数据，其中包括在长达一年（340天）的人类太空飞行中发生的变化的多尺度组学研究。嵌入NASATwins数据中的是与脂肪酸代谢相关的特定分析物。
在太空中1年内检查单个人中的长链脂肪酸去饱和酶和延伸酶。
一对男性双胞胎在国际空间站（ISS）上飞行了一年，而他的单卵双胞胎则是基因匹配的地面对照.纵向评估包括基因组，epige-nome,转录组，蛋白质组，代谢组，微生物组,和免疫组在任务期间，以及前后6个月。基因特异性脂肪酸去饱和酶和延伸酶转录组数据(FADSl、FADS2、ELOVL2和ELOVL5)从源自白细胞级分的非靶向RNA-seq测量中提取。
对于CD8，CD19和淋巴细胞耗竭（LD）细胞部分，延长酶和去饱和酶的大多数数据显示出相对相似的表达谱（R2>0.6）。表明受试者内部和受试者之间功能的总体保守性。在某些情况下观察到细胞类型和时间特异性，并且在加工的RNA的聚腺苷酸化(polyA)部分与核糖耗尽的(核糖-)部分之间的一些差异也是明显的。飞行受试者在几乎所有细胞类型中都显示出脂肪酸代谢过程途径的更强富集（柱，CD4，CD8，CPT，andLD),尤其是在RNA的核糖耗尽部分中，还有RNA的polyA+部分。跨三个相关脂肪酸代谢途径的基因集富集分析（GSEA）测量显示地面和飞行对象之间存在差异。
在太空中，去饱和酶和延伸酶基因表达似乎没有与1年相关的持续改变。然而,这些数据提供了细胞脂质代谢可以对太空飞行做出反应和动态的证据，即使它看起来是细胞类型和上下文特定的，最值得注意的是在测量的RNA分数和收集方案方面。这些结果也为所选基因表达的中速尖峰提供了新的证据，这可能表明在太空飞行期间对特定攻击的瞬态响应。
在太空中1年内检查单个人中的长链脂肪酸去饱和酶和延伸酶。
一对男性双胞胎在国际空间站（ISS）上飞行了一年，而他的单卵双胞胎则是基因匹配的地面对照.纵向评估包括基因组，epige-nome,转录组，蛋白质组，代谢组，微生物组,和免疫组在任务期间，以及前后6个月。基因特异性脂肪酸去饱和酶和延伸酶转录组数据(FADSl、FADS2、ELOVL2和ELOVL5)从源自白细胞级分的非靶向RNA-seq测量中提取。
对于CD8，CD19和淋巴细胞耗竭（LD）细胞部分，延长酶和去饱和酶的大多数数据显示出相对相似的表达谱（R2>0.6）。表明受试者内部和受试者之间功能的总体保守性。在某些情况下观察到细胞类型和时间特异性，并且在加工的RNA的聚腺苷酸化(polyA)部分与核糖耗尽的(核糖-)部分之间的一些差异也是明显的。飞行受试者在几乎所有细胞类型中都显示出脂肪酸代谢过程途径的更强富集（柱，CD4，CD8，CPT，andLD),尤其是在RNA的核糖耗尽部分中，还有RNA的polyA+部分。跨三个相关脂肪酸代谢途径的基因集富集分析（GSEA）测量显示地面和飞行对象之间存在差异。
在太空中，去饱和酶和延伸酶基因表达似乎没有与1年相关的持续改变。然而,这些数据提供了细胞脂质代谢可以对太空飞行做出反应和动态的证据，即使它看起来是细胞类型和上下文特定的，最值得注意的是在测量的RNA分数和收集方案方面。这些结果也为所选基因表达的中速尖峰提供了新的证据，这可能表明在太空飞行期间对特定攻击的瞬态响应。
