Long-read isoform sequencing reveals tissue-specific isoform expression between active and hibernating brown bears (Ursus arctos).
Long-read isoform sequencing reveals tissue-specific isoform expression between active and hibernating brown bears (Ursus arctos).
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DOI：
10.1093/g3journal/jkab422
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发表时间：
2022-03-04
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影响因子：
--
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了解棕熊（Ursus arctos）的冬眠可以帮助我们了解一些人类疾病。在冬眠期间，棕熊会经历胰岛素抵抗、身体不活动、极度心动过缓、肥胖和不排尿的时期。这些状态密切模仿人类疾病的方面，如2型糖尿病，肌肉萎缩，以及肾和心脏衰竭。这些状态从冬眠到活跃季节的可逆性使得能够识别对人类具有可能治疗价值的介质。最近的研究已经确定了在熊的活跃和冬眠季节之间差异表达的基因和途径。然而，鲜为人知的是，冬眠生理基因异构体的差异表达的作用。为了识别不同的和新的mRNA亚型，全长RNA测序（Iso-Seq）进行脂肪，骨骼肌和肝脏从三个单独的熊在活跃和冬眠季节采样。通过将其与Iso-Seq数据相结合，改进了现有的参考基因组注释。来自六个个体的短读RNA测序数据被映射到新的参考注释，以量化组织和季节之间的差异异构体使用（DIU）。我们确定了差异表达的异构体在所有三种组织中，在不同程度上。无论基因是否差异表达，脂肪具有高水平的DIU和亚型转换。我们的分析表明，DIU，即使在差异基因表达的情况下，是一个重要的机制，调节基因在冬眠期间。这些发现证明了异构体表达研究的价值，并将作为深入探索冬眠生物学的基础。
Understanding hibernation in brown bears (Ursus arctos) can provide insight into some human diseases. During hibernation, brown bears experience periods of insulin resistance, physical inactivity, extreme bradycardia, obesity, and the absence of urine production. These states closely mimic aspects of human diseases such as type 2 diabetes, muscle atrophy, as well as renal and heart failure. The reversibility of these states from hibernation to active season enables the identification of mediators with possible therapeutic value for humans. Recent studies have identified genes and pathways that are differentially expressed between active and hibernation seasons in bears. However, little is known about the role of differential expression of gene isoforms on hibernation physiology. To identify both distinct and novel mRNA isoforms, full-length RNA-sequencing (Iso-Seq) was performed on adipose, skeletal muscle, and liver from three individual bears sampled during both active and hibernation seasons. The existing reference genome annotation was improved by combining it with the Iso-Seq data. Short-read RNA-sequencing data from six individuals were mapped to the new reference annotation to quantify differential isoform usage (DIU) between tissues and seasons. We identified differentially expressed isoforms in all three tissues, to varying degrees. Adipose had a high level of DIU with isoform switching, regardless of whether the genes were differentially expressed. Our analyses revealed that DIU, even in the absence of differential gene expression, is an important mechanism for modulating genes during hibernation. These findings demonstrate the value of isoform expression studies and will serve as the basis for deeper exploration into hibernation biology.
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影响因子：
14.9
作者：
Mi H;Ebert D;Muruganujan A;Mills C;Albou LP;Mushayamaha T;Thomas PD
通讯作者：
Thomas PD
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
DOI：
10.1007/s00360-009-0421-x
发表时间：
2010-03-01
影响因子：
2
作者：
Nelson, O. Lynne;Robbins, Charles T.
通讯作者：
Robbins, Charles T.
影响因子：
5.9
作者：
Janseng, Heiko T.;Trojahn, Shawn;Kelley, Joanna L.
通讯作者：
Kelley, Joanna L.
影响因子：
3.7
作者：
Byrne, Ashley;Supple, Megan A.;Vollmers, Christopher
通讯作者：
Vollmers, Christopher