Cell Type-Specific Chromatin Signatures Underline Regulatory DNA Elements in Human Induced Pluripotent Stem Cells and Somatic Cells

被引:17
|
作者
Zhao, Ming-Tao [1 ]
Shao, Ning-Yi [1 ]
Hu, Shijun [2 ]
Ma, Ning [1 ]
Srinivasan, Rajini [3 ]
Jahanbani, Fereshteh [4 ]
Lee, Jaecheol [1 ]
Zhang, Sophia L. [1 ]
Snyder, Michael P. [4 ]
Wu, Joseph C. [1 ]
机构
[1] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford Cardiovasc Inst,Dept Med,Div Cardiol, Stanford, CA 94305 USA
[2] Soochow Univ, Inst Cardiovasc Sci, Affiliated Hosp 1, Dept Cardiovasc Surg, Suzhou 215000, Jiangsu, Peoples R China
[3] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA
[4] Stanford Univ, Sch Med, Dept Genet, 300 Pasteur Dr,M-344, Stanford, CA 94305 USA
基金
美国国家卫生研究院;
关键词
cardiac progenitor cells; endothelial cells; epigenetics; fibroblasts; human iPSCs; humans; stem cells; POLYMORPHIC VENTRICULAR-TACHYCARDIA; ATRIAL-FIBRILLATION; ARRHYTHMOGENESIS; INFLAMMATION; MICE;
D O I
10.1161/CIRCRESAHA.117.311367
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Rationale: Regulatory DNA elements in the human genome play important roles in determining the transcriptional abundance and spatiotemporal gene expression during embryonic heart development and somatic cell reprogramming. It is not well known how chromatin marks in regulatory DNA elements are modulated to establish cell type-specific gene expression in the human heart. Objective: We aimed to decipher the cell type-specific epigenetic signatures in regulatory DNA elements and how they modulate heart-specific gene expression. Methods and Results: We profiled genome-wide transcriptional activity and a variety of epigenetic marks in the regulatory DNA elements using massive RNA-seq (n=12) and ChIP-seq (chromatin immunoprecipitation combined with high-throughput sequencing; n=84) in human endothelial cells (CD31(+)CD144(+)), cardiac progenitor cells (Sca-1(+)), fibroblasts (DDR2(+)), and their respective induced pluripotent stem cells. We uncovered 2 classes of regulatory DNA elements: class I was identified with ubiquitous enhancer (H3K4me1) and promoter (H3K4me3) marks in all cell types, whereas class II was enriched with H3K4me1 and H3K4me3 in a cell type-specific manner. Both class I and class II regulatory elements exhibited stimulatory roles in nearby gene expression in a given cell type. However, class I promoters displayed more dominant regulatory effects on transcriptional abundance regardless of distal enhancers. Transcription factor network analysis indicated that human induced pluripotent stem cells and somatic cells from the heart selected their preferential regulatory elements to maintain cell type-specific gene expression. In addition, we validated the function of these enhancer elements in transgenic mouse embryos and human cells and identified a few enhancers that could possibly regulate the cardiac-specific gene expression. Conclusions: Given that a large number of genetic variants associated with human diseases are located in regulatory DNA elements, our study provides valuable resources for deciphering the epigenetic modulation of regulatory DNA elements that fine-tune spatiotemporal gene expression in human cardiac development and diseases.
引用
收藏
页码:1237 / 1250
页数:14
相关论文
共 50 条
  • [31] Single cell eQTL analysis identifies cell type-specific genetic control of gene expression in fibroblasts and reprogrammed induced pluripotent stem cells
    Neavin, Drew
    Nguyen, Quan
    Daniszewski, Maciej S.
    Liang, Helena H.
    Chiu, Han Sheng
    Wee, Yong Kiat
    Senabouth, Anne
    Lukowski, Samuel W.
    Crombie, Duncan E.
    Lidgerwood, Grace E.
    Hernandez, Damian
    Vickers, James C.
    Cook, Anthony L.
    Palpant, Nathan J.
    Pebay, Alice
    Hewitt, Alex W.
    Powell, Joseph E.
    GENOME BIOLOGY, 2021, 22 (01)
  • [32] Single cell eQTL analysis identifies cell type-specific genetic control of gene expression in fibroblasts and reprogrammed induced pluripotent stem cells
    Drew Neavin
    Quan Nguyen
    Maciej S. Daniszewski
    Helena H. Liang
    Han Sheng Chiu
    Yong Kiat Wee
    Anne Senabouth
    Samuel W. Lukowski
    Duncan E. Crombie
    Grace E. Lidgerwood
    Damián Hernández
    James C. Vickers
    Anthony L. Cook
    Nathan J. Palpant
    Alice Pébay
    Alex W. Hewitt
    Joseph E. Powell
    Genome Biology, 22
  • [33] Evaluation of Residual Human-Induced Pluripotent Stem Cells in Human Chondrocytes by Cell Type-Specific Glycosphingolipid Glycome Analysis Based on the Aminolysis-SALSA Technique
    Miyazaki, Takuji
    Hanamatsu, Hisatoshi
    Xu, Liang
    Onodera, Tomohiro
    Furukawa, Jun-ichi
    Homan, Kentaro
    Baba, Rikiya
    Kawasaki, Toshisuke
    Iwasaki, Norimasa
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (01)
  • [34] Generation of Pluripotent Stem Cells Using Somatic Cell Nuclear Transfer and Induced Pluripotent Somatic Cells from African Green Monkeys
    Chung, Young Gie
    Seay, Montrell
    Elsworth, John D.
    Redmond, D. Eugene
    STEM CELLS AND DEVELOPMENT, 2020, 29 (19) : 1294 - 1307
  • [35] Chemically Induced Reprogramming of Somatic Cells to Pluripotent Stem Cells and Neural Cells
    Biswas, Dhruba
    Jiang, Peng
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2016, 17 (02)
  • [36] Direct generation of human naive induced pluripotent stem cells from somatic cells in microfluidics
    Stefano Giulitti
    Marco Pellegrini
    Irene Zorzan
    Paolo Martini
    Onelia Gagliano
    Margherita Mutarelli
    Michael Johannes Ziller
    Davide Cacchiarelli
    Chiara Romualdi
    Nicola Elvassore
    Graziano Martello
    Nature Cell Biology, 2019, 21 : 275 - 286
  • [37] Direct generation of human naive induced pluripotent stem cells from somatic cells in microfluidics
    Giulitti, Stefano
    Pellegrini, Marco
    Zorzan, Irene
    Martini, Paolo
    Gagliano, Onelia
    Mutarelli, Margherita
    Ziller, Michael Johannes
    Cacchiarelli, Davide
    Romualdi, Chiara
    Elvassore, Nicola
    Martello, Graziano
    NATURE CELL BIOLOGY, 2019, 21 (02) : 275 - +
  • [38] Generation of Mouse and Human Induced Pluripotent Stem Cells (iPSC) from Primary Somatic Cells
    Lorenzo, I. M.
    Fleischer, A.
    Bachiller, D.
    STEM CELL REVIEWS AND REPORTS, 2013, 9 (04) : 435 - 450
  • [39] Effects of mechanical stimulation on the reprogramming of somatic cells into human-induced pluripotent stem cells
    Kim, Young Mi
    Kang, Yun Gyeong
    Park, So Hee
    Han, Myung-Kwan
    Kim, Jae Ho
    Shin, Ji Won
    Shin, Jung-Woog
    STEM CELL RESEARCH & THERAPY, 2017, 8
  • [40] Effects of mechanical stimulation on the reprogramming of somatic cells into human-induced pluripotent stem cells
    Young Mi Kim
    Yun Gyeong Kang
    So Hee Park
    Myung-Kwan Han
    Jae Ho Kim
    Ji Won Shin
    Jung-Woog Shin
    Stem Cell Research & Therapy, 8