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DOI | 10.1038/s41467-018-06803-z |
Defining human cardiac transcription factor hierarchies using integrated single-cell heterogeneity analysis | |
Churko, Jared M.1,2,3,4,5; Garg, Priyanka1,2,3,4; Treutlein, Barbara6; Venkatasubramanian, Meenakshi7; Wu, Haodi1,2,3,4; Lee, Jaecheol1,2,3,4; Wessells, Quinton N.1,2,3,4; Chen, Shih-Yu8; Chen, Wen-Yi1,2,3,4; Chetal, Kashish7; Mantalas, Gary6; Neff, Norma6; Jabart, Eric9,10; Sharma, Arun1,2,3,4; Nolan, Garry P.8; Salomonis, Nathan7; Wu, Joseph C.1,2,3,4 | |
2018-11-21 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have become a powerful tool for human disease modeling and therapeutic testing. However, their use remains limited by their immaturity and heterogeneity. To characterize the source of this heterogeneity, we applied complementary single-cell RNA-seq and bulk RNA-seq technologies over time during hiPSC cardiac differentiation and in the adult heart. Using integrated transcriptomic and splicing analysis, more than half a dozen distinct single-cell populations were observed, several of which were coincident at a single time-point, day 30 of differentiation. To dissect the role of distinct cardiac transcriptional regulators associated with each cell population, we systematically tested the effect of a gain or loss of three transcription factors (NR2F2, TBX5, and HEY2), using CRISPR genome editing and ChIP-seq, in conjunction with patch clamp, calcium imaging, and CyTOF analysis. These targets, data, and integrative genomics analysis methods provide a powerful platform for understanding in vitro cellular heterogeneity. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000450754900001 |
WOS关键词 | PLURIPOTENT STEM-CELLS ; GENE-EXPRESSION ; MASS CYTOMETRY ; FUNCTIONAL-PROPERTIES ; CARDIOMYOCYTES ; HEART ; MATURATION ; DIFFERENTIATION ; PROGENITORS ; SYSTEM |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204051 |
专题 | 资源环境科学 |
作者单位 | 1.Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA; 2.Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA; 3.Stanford Univ, Dept Med, Stanford, CA 94305 USA; 4.Stanford Univ, Dept Radiol, Stanford, CA 94305 USA; 5.Univ Arizona, Dept Cellular & Mol Med, Tucson, AZ 85724 USA; 6.Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA; 7.Cincinnati Childrens Hosp Med Ctr, Div Biomed Informat, Cincinnati, OH 45229 USA; 8.Stanford Univ, Sch Med, Dept Microbiol & Immunol, Baxter Lab Stem Cell Biol, Stanford, CA 94305 USA; 9.Zephyrus Biosci Inc, 820 Heinz Ave, Berkeley, CA 94710 USA; 10.Stanford Univ, Dept Biochem, Stanford, CA 94305 USA |
推荐引用方式 GB/T 7714 | Churko, Jared M.,Garg, Priyanka,Treutlein, Barbara,et al. Defining human cardiac transcription factor hierarchies using integrated single-cell heterogeneity analysis[J]. NATURE COMMUNICATIONS,2018,9. |
APA | Churko, Jared M..,Garg, Priyanka.,Treutlein, Barbara.,Venkatasubramanian, Meenakshi.,Wu, Haodi.,...&Wu, Joseph C..(2018).Defining human cardiac transcription factor hierarchies using integrated single-cell heterogeneity analysis.NATURE COMMUNICATIONS,9. |
MLA | Churko, Jared M.,et al."Defining human cardiac transcription factor hierarchies using integrated single-cell heterogeneity analysis".NATURE COMMUNICATIONS 9(2018). |
条目包含的文件 | 条目无相关文件。 |
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