Single-Cell Resolution of Temporal Gene Expression during Heart Development

被引：379

作者：

DeLaughter, Daniel M. ^{[1
]}

Bick, Alexander G. ^{[1
]}

Wakimoto, Hiroko ^{[1
]}

McKean, David ^{[1
]}

Gorham, Joshua M. ^{[1
]}

Kathiriya, Irian S. ^{[2
,3
]}

Hinson, John T. ^{[4
]}

Homsy, Jason ^{[1
]}

Gray, Jesse ^{[1
]}

Pu, William ^{[5
,6
]}

Bruneau, Benoit G. ^{[2
,7
]}

Seidman, J. G. ^{[1
]}

Seidman, Christine E. ^{[1
,8
]}

机构：

[1] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA

[2] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA

[3] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 92868 USA

[4] Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA

[5] Harvard Med Sch, Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA

[6] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[7] Univ Calif San Francisco, Cardiovasc Res Inst, Dept Pediat, San Francisco, CA 94158 USA

[8] Brigham & Womens Hosp, Div Cardiovasc, Howard Hughes Med Inst, 75 Francis St, Boston, MA 02115 USA

来源：

DEVELOPMENTAL CELL | 2016年 / 39卷 / 04期

关键词：

RNA-SEQ; IN-VIVO; MUTATIONS; LINEAGE; DISEASE; PROTEIN; NKX2-5; TBX5; CARDIOMYOCYTES; IDENTIFICATION;

D O I：

10.1016/j.devcel.2016.10.001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Activation of complex molecular programs in specific cell lineages governs mammalian heart development, from a primordial linear tube to a four-chamber organ. To characterize lineage-specific, spatiotemporal developmental programs, we performed single-cell RNA sequencing of >1,200 murine cells isolated at seven time points spanning embryonic day 9.5 (primordial heart tube) to postnatal day 21 (mature heart). Using unbiased transcriptional data, we classified cardiomyocytes, endothelial cells, and fibroblast-enriched cells, thus identifying markers for temporal and chamber-specific developmental programs. By harnessing these datasets, we defined developmental ages of human and mouse pluripotent stem-cell-derived cardiomyocytes and characterized lineage-specific maturation defects in hearts of mice with heterozygous mutations in Nkx2.5 that cause human heart malformations. This spatiotemporal transcriptome analysis of heart development reveals lineage-specific gene programs underlying normal cardiac development and congenital heart disease.

引用

页码：480 / 490

页数：11

共 55 条

[1]

TEF-1 and C/EBPβ are major p38α MAR-regulated transcription factors in proliferating cardiomyocytes [J].

Ambrosino, Concetta ;

Iwata, Tomoko ;

Scafoglio, Claudio ;

Mallardo, Massimo ;

Klein, Ruediger ;

Nebreda, Angel R. .

BIOCHEMICAL JOURNAL, 2006, 396 :163-172

[2]

RNA-Mediated Regulation of HMGA1 Function [J].

Benecke, Arndt G. ;

Eilebrecht, Sebastian .

BIOMOLECULES, 2015, 5 (02) :943-957

[3]

Cardiac septal and valvular dysmorphogenesis in mice heterozygous for mutations in the homeobox gene Nkx2-5 [J].

Biben, C ;

Weber, R ;

Kesteven, S ;

Stanley, E ;

McDonald, L ;

Elliott, DA ;

Barnett, L ;

Köentgen, F ;

Robb, L ;

Feneley, M ;

Harvey, RP .

CIRCULATION RESEARCH, 2000, 87 (10) :888-895

[4]

Evolutionary Diversity of the Mitochondrial Calcium Uniporter [J].

Bick, Alexander G. ;

Calvo, Sarah E. ;

Mootha, Vamsi K. .

SCIENCE, 2012, 336 (6083) :886-886

[5]

NKX2-5 mutations causative for congenital heart disease retain functionality and are directed to hundreds of targets [J].

Bouveret, Romaric ;

Waardenberg, Ashley J. ;

Schonrock, Nicole ;

Ramialison, Mirana ;

Doan, Tram ;

de Jong, Danielle ;

Bondue, Antoine ;

Kaur, Gurpreet ;

Mohamed, Stephanie ;

Fonoudi, Hananeh ;

Chen, Chiann-mun ;

Wouters, Merridee A. ;

Bhattacharya, Shoumo ;

Plachta, Nicolas ;

Dunwoodie, Sally L. ;

Chapman, Gavin ;

Blanpain, Cedric ;

Harvey, Richard P. .

ELIFE, 2015, 4

[6]

Identification and characterization of KLHL4, a novel human homologue of the Drosophila Kelch gene that maps within the X-linked cleft palate and ankyloglossia (CPX) critical region [J].

Braybrook, C ;

Warry, G ;

Howell, G ;

Arnason, A ;

Bjornsson, A ;

Moore, GE ;

Ross, MT ;

Stanier, P .

GENOMICS, 2001, 72 (02) :128-136

[7]

A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease [J].

Bruneau, BG ;

Nemer, G ;

Schmitt, JP ;

Charron, F ;

Robitaille, L ;

Caron, S ;

Conner, DA ;

Gessler, M ;

Nemer, M ;

Seidman, CE ;

Seidman, JG .

CELL, 2001, 106 (06) :709-721

[8]

Computational analysis of cell-to-cell heterogeneity in single-cell RNA-sequencing data reveals hidden subpopulations of cells [J].

Buettner, Florian ;

Natarajan, Kedar N. ;

Casale, F. Paolo ;

Proserpio, Valentina ;

Scialdone, Antonio ;

Theis, Fabian J. ;

Teichmann, Sarah A. ;

Marioni, John C. ;

Stegie, Oliver .

NATURE BIOTECHNOLOGY, 2015, 33 (02) :155-160

[9]

Genomic imbalances associated with mullerian aplasia [J].

Cheroki, C. ;

Krepischi-Santos, A. C. V. ;

Szuhai, K. ;

Brenner, V. ;

Kim, C. A. E. ;

Otto, P. A. ;

Rosenberg, C. .

JOURNAL OF MEDICAL GENETICS, 2008, 45 (04) :228-232

[10]

Microfibril-associated Glycoprotein 2 (MAGP2) Loss of Function Has Pleiotropic Effects in Vivo [J].

Combs, Michelle D. ;

Knutsen, Russell H. ;

Broekelmann, Thomas J. ;

Toennies, Holly M. ;

Brett, Thomas J. ;

Miller, Chantel A. ;

Kober, Daniel L. ;

Craft, Clarissa S. ;

Atkinson, Jeffrey J. ;

Shipley, J. Michael ;

Trask, Barbara C. ;

Mecham, Robert P. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (40) :28869-28880

← 1 2 3 4 5 6 →