Single-nucleus transcriptomic survey of cell diversity and functional maturation in postnatal mammalian hearts.
Single-nucleus transcriptomic survey of cell diversity and functional maturation in postnatal mammalian hearts.
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DOI：
10.1101/gad.316802.118
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发表时间：
2018-10-01
影响因子：
10.5
通讯作者：
Pei L
中科院分区：
文献类型：
--
作者：
Hu P;Liu J;Zhao J;Wilkins BJ;Lupino K;Wu H;Pei L
Hu等人应用sNucDrop-seq，一种基于液滴微流体的大规模并行snRNA-seq方法，研究了健康和疾病状态下出生后成熟小鼠心脏的转录景观。理解心脏生物学和疾病的一个根本挑战是，在细胞类型组成和功能状态的显着异质性还没有得到很好的表征，在成熟和患病的哺乳动物心脏的单细胞分辨率。大规模并行单核RNA测序（snRNA-seq）已经成为解决这些问题的有力工具，通过询问从新鲜或冷冻组织中分离的数万个细胞核的转录组。snRNA-seq克服了从复杂组织（包括成熟的哺乳动物心脏）中分离完整单细胞的技术挑战;减少了容易解离的细胞类型的偏倚恢复;并最大限度地减少了全细胞解离过程中的异常基因表达。在这里，我们应用sNucDrop-seq，一种基于液滴微流控的大规模并行snRNA-seq方法，来研究健康和疾病状态下出生后成熟小鼠心脏的转录景观。通过分析近20，000个细胞核的转录组，我们识别了主要和罕见的心脏细胞类型，并揭示了出生后发育心脏中心肌细胞、成纤维细胞和内皮细胞的显着异质性。当应用于儿童线粒体心肌病的小鼠模型时，我们发现了单核分辨率下心脏转录景观的深刻细胞类型特异性修饰，包括亚型组成，成熟状态和每种细胞类型的功能重塑的变化。此外，我们使用sNucDrop-seq来破译GDF 15的心脏细胞类型特异性基因调控网络（GRN），GDF 15是一种心脏来源的激素和临床上重要的心脏病诊断生物标志物。总之，我们的研究结果为研究心脏生物学提供了丰富的资源，并使用广泛适用于许多生物医学领域的方法提供了对心脏病的新见解。
Hu et al. applied sNucDrop-seq, a droplet microfluidics-based massively parallel snRNA-seq method, to investigate the transcriptional landscape of postnatal maturing mouse hearts in both healthy and disease states. A fundamental challenge in understanding cardiac biology and disease is that the remarkable heterogeneity in cell type composition and functional states have not been well characterized at single-cell resolution in maturing and diseased mammalian hearts. Massively parallel single-nucleus RNA sequencing (snRNA-seq) has emerged as a powerful tool to address these questions by interrogating the transcriptome of tens of thousands of nuclei isolated from fresh or frozen tissues. snRNA-seq overcomes the technical challenge of isolating intact single cells from complex tissues, including the maturing mammalian hearts; reduces biased recovery of easily dissociated cell types; and minimizes aberrant gene expression during the whole-cell dissociation. Here we applied sNucDrop-seq, a droplet microfluidics-based massively parallel snRNA-seq method, to investigate the transcriptional landscape of postnatal maturing mouse hearts in both healthy and disease states. By profiling the transcriptome of nearly 20,000 nuclei, we identified major and rare cardiac cell types and revealed significant heterogeneity of cardiomyocytes, fibroblasts, and endothelial cells in postnatal developing hearts. When applied to a mouse model of pediatric mitochondrial cardiomyopathy, we uncovered profound cell type-specific modifications of the cardiac transcriptional landscape at single-nucleus resolution, including changes of subtype composition, maturation states, and functional remodeling of each cell type. Furthermore, we employed sNucDrop-seq to decipher the cardiac cell type-specific gene regulatory network (GRN) of GDF15, a heart-derived hormone and clinically important diagnostic biomarker of heart disease. Together, our results present a rich resource for studying cardiac biology and provide new insights into heart disease using an approach broadly applicable to many fields of biomedicine.
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影响因子：
29
作者：
Li T;Zhang Z;Kolwicz SC Jr;Abell L;Roe ND;Kim M;Zhou B;Cao Y;Ritterhoff J;Gu H;Raftery D;Sun H;Tian R
通讯作者：
Tian R
影响因子：
82.9
作者：
Emmerson, Paul J.;Wang, Feng;Wu, Xinle
通讯作者：
Wu, Xinle
影响因子：
11.8
作者：
Li, Guang;Xu, Adele;Wu, Sean M.
通讯作者：
Wu, Sean M.
影响因子：
11.8
作者：
DeLaughter, Daniel M.;Bick, Alexander G.;Wakimoto, Hiroko;McKean, David;Gorham, Joshua M.;Kathiriya, Irian S.;Hinson, John T.;Homsy, Jason;Gray, Jesse;Pu, William;Bruneau, Benoit G.;Seidman, J. G.;Seidman, Christine E.
通讯作者：
Seidman, Christine E.
DOI：
10.1152/ajpheart.00514.2007
发表时间：
2007-09-01
影响因子：
4.8
作者：
Banerjee, Indroneal;Fuseler, John W.;Baudino, Troy A.
通讯作者：
Baudino, Troy A.