Single-Cell Resolution of Temporal Gene Expression during Heart Development

Developmental Cell

Volumn 39, Issue 4, 2016, Pages 480-490

  DeLaughter, Daniel M ^a   Bick, Alexander G ^a   Wakimoto, Hiroko ^a   McKean, David ^a   Gorham, Joshua M ^a   Kathiriya, Irfan S ^b,c   Hinson, John T ^d   Homsy, Jason ^a   Gray, Jesse ^a   Pu, William ^e,f   Bruneau, Benoit G ^b,c   Seidman, J G ^a   Seidman, Christine E ^a,d  

^a HARVARD MEDICAL SCHOOL   (United States)

^b GLADSTONE INSTITUTE OF CARDIOVASCULAR DISEASE   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d BRIGHAM AND WOMEN S HOSPITAL   (United States)

^e BOSTON CHILDREN S HOSPITAL   (United States)

^f HARVARD STEM CELL INSTITUTE   (United States)

Author keywords

atria; cardiogenesis; cardiomyocyte maturation; ECM; heart; Nkx2.5; RNA seq; single cell; ventricle

Indexed keywords

TRANSCRIPTOME; HOMEOBOX PROTEIN NKX-2.5; NKX2-5 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CARDIAC MUSCLE CELL; CELL LINEAGE; CELL SPECIFICITY; CONGENITAL HEART DISEASE; CONGENITAL HEART MALFORMATION; DEVELOPMENTAL STAGE; EMBRYO; ENDOTHELIUM CELL; FEMALE; FETUS; GENE; GENE EXPRESSION; GENE MUTATION; GENETIC TRANSCRIPTION; HAPLOINSUFFICIENCY; HEART DEVELOPMENT; HEART FIBROBLAST; HETEROZYGOTE; HUMAN; HUMAN CELL; MALE; MOUSE; NEWBORN; NKX2.5 GENE; NONHUMAN; PERINATAL PERIOD; PLURIPOTENT STEM CELL; PRIMORDIUM; PRIORITY JOURNAL; RNA SEQUENCE; SINGLE CELL ANALYSIS; ANIMAL; CELL DIFFERENTIATION; CYTOLOGY; EMBRYOLOGY; FIBROBLAST; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; HEART; HEART ATRIUM; HEART VENTRICLE; METABOLISM; PROCEDURES; SEQUENCE ANALYSIS; TIME FACTOR;

ANIMALS; CELL DIFFERENTIATION; CELL LINEAGE; ENDOTHELIAL CELLS; FIBROBLASTS; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HAPLOINSUFFICIENCY; HEART; HEART ATRIA; HEART VENTRICLES; HOMEOBOX PROTEIN NKX-2.5; HUMANS; MICE; MYOCYTES, CARDIAC; SEQUENCE ANALYSIS, RNA; SINGLE-CELL ANALYSIS; TIME FACTORS; TRANSCRIPTOME;

EID: 84997343111     PISSN: 15345807     EISSN: 18781551     Source Type: Journal    
DOI: 10.1016/j.devcel.2016.10.001     Document Type: Article

References (56)

1. Ambrosino, C., Iwata, T., Scafoglio, C., Mallardo, M., Klein, R., Nebreda, A.R., TEF-1 and C/EBPbeta are major p38alpha MAPK-regulated transcription factors in proliferating cardiomyocytes. Biochem. J. 396 (2006), 163–172.
2. Ashraf, H., Pradhan, L., Chang, E.I., Terada, R., Ryan, N.J., Briggs, L.E., Chowdhury, R., Zarate, M.A., Sugi, Y., Nam, H.J., et al. A mouse model of human congenital heart disease: high incidence of diverse cardiac anomalies and ventricular noncompaction produced by heterozygous Nkx2-5 homeodomain missense mutation. Circ. Cardiovasc. Genet. 7 (2014), 423–433.
3. Benecke, A.G., Eilebrecht, S., RNA-mediated regulation of HMGA1 function. Biomolecules 5 (2015), 943–957.
4. Biben, C., Weber, R., Kesteven, S., Stanley, E., McDonald, L., Elliott, D.A., Barnett, L., Koentgen, F., Robb, L., Feneley, M., et al. Cardiac septal and valvular dysmorphogenesis in mice heterozygous for mutations in the homeobox gene Nkx2-5. Circ. Res. 87 (2000), 888–895.
5. Bick, A.G., Calvo, S.E., Mootha, V.K., Evolutionary diversity of the mitochondrial calcium uniporter. Science, 336, 2012, 886.
6. Bouveret, R., Waardenberg, A.J., Schonrock, N., Ramialison, M., Doan, T., de Jong, D., Bondue, A., Kaur, G., Mohamed, S., Fonoudi, H., et al. NKX2-5 mutations causative for congenital heart disease retain functionality and are directed to hundreds of targets. Elife, 4, 2015, e06942.
7. Braybrook, C., Warry, G., Howell, G., Arnason, A., Bjornsson, A., Moore, G.E., Ross, M.T., Stanier, P., 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. Genomics 72 (2001), 128–136.
8. Bruneau, B.G., Nemer, G., Schmitt, J.P., Charron, F., Robitaille, L., Caron, S., Conner, D.A., Gessler, M., Nemer, M., Seidman, C.E., et al. A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease. Cell 106 (2001), 709–721.
9. Buettner, F., Natarajan, K.N., Casale, F.P., Proserpio, V., Scialdone, A., Theis, F.J., Teichmann, S.A., Marioni, J.C., Stegle, O., Computational analysis of cell-to-cell heterogeneity in single-cell RNA-sequencing data reveals hidden subpopulations of cells. Nat. Biotechnol. 33 (2015), 155–160.
10. Cheroki, C., Krepischi-Santos, A.C., Szuhai, K., Brenner, V., Kim, C.A., Otto, P.A., Rosenberg, C., Genomic imbalances associated with mullerian aplasia. J. Med. Genet. 45 (2008), 228–232.
11. Combs, M.D., Knutsen, R.H., Broekelmann, T.J., Toennies, H.M., Brett, T.J., Miller, C.A., Kober, D.L., Craft, C.S., Atkinson, J.J., Shipley, J.M., et al. Microfibril-associated glycoprotein 2 (MAGP2) loss of function has pleiotropic effects in vivo. J. Biol. Chem. 288 (2013), 28869–28880.
12. Dahle, O., Kumar, A., Kuehn, M.R., Nodal signaling recruits the histone demethylase Jmjd3 to counteract polycomb-mediated repression at target genes. Sci. Signal., 3, 2010, ra48.
13. DeLaughter, D.M., Christodoulou, D.C., Robinson, J.Y., Seidman, C.E., Baldwin, H.S., Seidman, J.G., Barnett, J.V., Spatial transcriptional profile of the chick and mouse endocardial cushions identify novel regulators of endocardial EMT in vitro. J. Mol. Cell Cardiol. 59 (2013), 196–204.
14. Desplantez, T., McCain, M.L., Beauchamp, P., Rigoli, G., Rothen-Rutishauser, B., Parker, K.K., Kleber, A.G., Connexin43 ablation in foetal atrial myocytes decreases electrical coupling, partner connexins, and sodium current. Cardiovasc. Res. 94 (2012), 58–65.
15. Diez-Roux, G., Banfi, S., Sultan, M., Geffers, L., Anand, S., Rozado, D., Magen, A., Canidio, E., Pagani, M., Peluso, I., et al. A high-resolution anatomical atlas of the transcriptome in the mouse embryo. PLoS Biol., 9, 2011, e1000582.
16. Elliott, D.A., Kirk, E.P., Yeoh, T., Chandar, S., McKenzie, F., Taylor, P., Grossfeld, P., Fatkin, D., Jones, O., Hayes, P., et al. Cardiac homeobox gene NKX2-5 mutations and congenital heart disease: associations with atrial septal defect and hypoplastic left heart syndrome. J. Am. Coll. Cardiol. 41 (2003), 2072–2076.
17. Grun, D., Lyubimova, A., Kester, L., Wiebrands, K., Basak, O., Sasaki, N., Clevers, H., van Oudenaarden, A., Single-cell messenger RNA sequencing reveals rare intestinal cell types. Nature 525 (2015), 251–255.
18. Homsy, J., Zaidi, S., Shen, Y., Ware, J.S., Samocha, K.E., Karczewski, K.J., DePalma, S.R., McKean, D., Wakimoto, H., Gorham, J., et al. De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies. Science 350 (2015), 1262–1266.
19. Huang, D.W., Sherman, B.T., Tan, Q., Kir, J., Liu, D., Bryant, D., Guo, Y., Stephens, R., Baseler, M.W., Lane, H.C., et al. DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res. 35 (2007), W169–W175.
20. Ieda, M., Tsuchihashi, T., Ivey, K.N., Ross, R.S., Hong, T.T., Shaw, R.M., Srivastava, D., Cardiac fibroblasts regulate myocardial proliferation through beta1 integrin signaling. Dev. Cell 16 (2009), 233–244.
21. Jain, R., Li, D., Gupta, M., Manderfield, L.J., Ifkovits, J.L., Wang, Q., Liu, F., Liu, Y., Poleshko, A., Padmanabhan, A., et al. HEART DEVELOPMENT. Integration of Bmp and Wnt signaling by Hopx specifies commitment of cardiomyoblasts. Science, 348, 2015, aaa6071.
22. Jang, D.G., Sim, H.J., Song, E.K., Medina-Ruiz, S., Seo, J.K., Park, T.J., A thioredoxin fold protein Sh3bgr regulates Enah and is necessary for proper sarcomere formation. Dev. Biol. 405 (2015), 1–9.
23. Jensen, B., Wang, T., Christoffels, V.M., Moorman, A.F., Evolution and development of the building plan of the vertebrate heart. Biochim. Biophys. Acta 1833 (2013), 783–794.
24. Kasahara, H., Bartunkova, S., Schinke, M., Tanaka, M., Izumo, S., Cardiac and extracardiac expression of Csx/Nkx2.5 homeodomain protein. Circ. Res. 82 (1998), 936–946.
25. Kiselev, V.Y., Kirschner, K., Schaub, M.T., Andrews, T., Chandra, T., Natarajan, K.N., Reik, W., Barahona, M., Green, A.R., Hemberg, M., SC3-consensus clustering of single-cell RNA-Seq data. bioRxiv, 2016, 10.1101/036558.
26. Koo, J.H., Smiley, M.A., Lovering, R.M., Margolis, F.L., Bex1 knock out mice show altered skeletal muscle regeneration. Biochem. Biophys. Res. Commun. 363 (2007), 405–410.
27. Koshiba-Takeuchi, K., Takeuchi, J.K., Arruda, E.P., Kathiriya, I.S., Mo, R., Hui, C.C., Srivastava, D., Bruneau, B.G., Cooperative and antagonistic interactions between Sall4 and Tbx5 pattern the mouse limb and heart. Nat. Genet. 38 (2006), 175–183.
28. Kuppusamy, K.T., Jones, D.C., Sperber, H., Madan, A., Fischer, K.A., Rodriguez, M.L., Pabon, L., Zhu, W.Z., Tulloch, N.L., Yang, X., et al. Let-7 family of microRNA is required for maturation and adult-like metabolism in stem cell-derived cardiomyocytes. Proc. Natl. Acad. Sci. USA 112 (2015), E2785–E2794.
29. Li, G., Plonowska, K., Kuppusamy, R., Sturzu, A., Wu, S.M., Identification of cardiovascular lineage descendants at single-cell resolution. Development 142 (2015), 846–857.
30. Liang, B., Soka, M., Christensen, A.H., Olesen, M.S., Larsen, A.P., Knop, F.K., Wang, F., Nielsen, J.B., Andersen, M.N., Humphreys, D., et al. Genetic variation in the two-pore domain potassium channel, TASK-1, may contribute to an atrial substrate for arrhythmogenesis. J. Mol. Cell Cardiol. 67 (2014), 69–76.
31. Liberatore, C.M., Searcy-Schrick, R.D., Yutzey, K.E., Ventricular expression of tbx5 inhibits normal heart chamber development. Dev. Biol. 223 (2000), 169–180.
32. Luo, M.H., Li, Y.S., Yang, K.P., Fibrosis of collagen I and remodeling of connexin 43 in atrial myocardium of patients with atrial fibrillation. Cardiology 107 (2007), 248–253.
33. Mayer, D.C., Leinwand, L.A., Sarcomeric gene expression and contractility in myofibroblasts. J. Cell Biol. 139 (1997), 1477–1484.
34. McKean, D.M., Homsy, J., Wakimoto, H., Patel, N., Gorham, J., DePalma, S.R., Ware, J.S., Zaidi, S., Ma, L., Patel, V., et al. Loss of RNA expression and allele-specific expression associated with congenital heart disease. Nat. Commun., 7, 2016, 12824.
35. Medic, S., Ziman, M., PAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas). PLoS One, 5, 2010, e9977.
36. Monzen, K., Ito, Y., Naito, A.T., Kasai, H., Hiroi, Y., Hayashi, D., Shiojima, I., Yamazaki, T., Miyazono, K., Asashima, M., et al. A crucial role of a high mobility group protein HMGA2 in cardiogenesis. Nat. Cell Biol. 10 (2008), 567–574.
37. Nash, D., Arrington, C.B., Kennedy, B.J., Yandell, M., Wu, W., Zhang, W., Ware, S., Jorde, L.B., Gruber, P.J., Yost, H.J., et al. Shared segment analysis and next-generation sequencing implicates the retinoic acid signaling pathway in total anomalous pulmonary venous return (TAPVR). PLoS One, 10, 2015, e0131514.
38. Niaudet, C., Hofmann, J.J., Mae, M.A., Jung, B., Gaengel, K., Vanlandewijck, M., Ekvarn, E., Salvado, M.D., Mehlem, A., Al Sayegh, S., et al. Gpr116 receptor regulates distinctive functions in pneumocytes and vascular endothelium. PLoS One, 10, 2015, e0137949.
39. Palencia-Desai, S., Rost, M.S., Schumacher, J.A., Ton, Q.V., Craig, M.P., Baltrunaite, K., Koenig, A.L., Wang, J., Poss, K.D., Chi, N.C., et al. Myocardium and BMP signaling are required for endocardial differentiation. Development 142 (2015), 2304–2315.
40. Pinto, A.R., Ilinykh, A., Ivey, M.J., Kuwabara, J.T., D'Antoni, M.L., Debuque, R., Chandran, A., Wang, L., Arora, K., Rosenthal, N.A., et al. Revisiting cardiac cellular composition. Circ. Res. 118 (2016), 400–409.
41. Pujades, C., Guez-Guez, B., Dunon, D., Melanoma cell adhesion molecule (MCAM) expression in the myogenic lineage during early chick embryonic development. Int. J. Dev. Biol. 46 (2002), 263–266.
42. Rousseeuw, P.J., Silhouettes: a graphical aid to the interpretation and validation of cluster analysis. J. Comput. Appl. Math. 20 (1987), 53–65.
43. Schott, J.J., Benson, D.W., Basson, C.T., Pease, W., Silberbach, G.M., Moak, J.P., Maron, B.J., Seidman, C.E., Seidman, J.G., Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science 281 (1998), 108–111.
44. Smith, C.M., Finger, J.H., Hayamizu, T.F., McCright, I.J., Xu, J., Berghout, J., Campbell, J., Corbani, L.E., Forthofer, K.L., Frost, P.J., et al. The mouse gene expression database (GXD): 2014 update. Nucleic Acids Res. 42 (2014), D818–D824.
45. Streets, A.M., Huang, Y., How deep is enough in single-cell RNA-seq?. Nat. Biotechnol. 32 (2014), 1005–1006.
46. Tanaka, M., Chen, Z., Bartunkova, S., Yamasaki, N., Izumo, S., The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development. Development 126 (1999), 1269–1280.
47. Thomas, T., Yamagishi, H., Overbeek, P.A., Olson, E.N., Srivastava, D., The bHLH factors, dHAND and eHAND, specify pulmonary and systemic cardiac ventricles independent of left-right sidedness. Dev. Biol. 196 (1998), 228–236.
48. Tian, Y., Yuan, L., Goss, A.M., Wang, T., Yang, J., Lepore, J.J., Zhou, D., Schwartz, R.J., Patel, V., Cohen, E.D., et al. Characterization and in vivo pharmacological rescue of a Wnt2-Gata6 pathway required for cardiac inflow tract development. Dev. Cell 18 (2010), 275–287.
49. Trapnell, C., Pachter, L., Salzberg, S.L., TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25 (2009), 1105–1111.
50. Trapnell, C., Cacchiarelli, D., Grimsby, J., Pokharel, P., Li, S., Morse, M., Lennon, N.J., Livak, K.J., Mikkelsen, T.S., Rinn, J.L., The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells. Nat. Biotechnol. 32 (2014), 381–386.
51. Treutlein, B., Brownfield, D.G., Wu, A.R., Neff, N.F., Mantalas, G.L., Espinoza, F.H., Desai, T.J., Krasnow, M.A., Quake, S.R., Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq. Nature 509 (2014), 371–375.
52. Vander Heiden, M.G., Locasale, J.W., Swanson, K.D., Sharfi, H., Heffron, G.J., Amador-Noguez, D., Christofk, H.R., Wagner, G., Rabinowitz, J.D., Asara, J.M., et al. Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science 329 (2010), 1492–1499.
53. Wagner, M., Siddiqui, M.A., Signal transduction in early heart development (I): cardiogenic induction and heart tube formation. Exp. Biol. Med. 232 (2007), 852–865.
54. Wamstad, J.A., Alexander, J.M., Truty, R.M., Shrikumar, A., Li, F., Eilertson, K.E., Ding, H., Wylie, J.N., Pico, A.R., Capra, J.A., et al. Dynamic and coordinated epigenetic regulation of developmental transitions in the cardiac lineage. Cell 151 (2012), 206–220.
55. Yang, M.Y., Hilton, M.B., Seaman, S., Haines, D.C., Nagashima, K., Burks, C.M., Tessarollo, L., Ivanova, P.T., Brown, H.A., Umstead, T.M., et al. Essential regulation of lung surfactant homeostasis by the orphan G protein-coupled receptor GPR116. Cell Rep. 3 (2013), 1457–1464.
56. Yuan, F., Qiu, X.B., Li, R.G., Qu, X.K., Wang, J., Xu, Y.J., Liu, X., Fang, W.Y., Yang, Y.Q., Liao, D.N., A novel NKX2-5 loss-of-function mutation predisposes to familial dilated cardiomyopathy and arrhythmias. Int. J. Mol. Med. 35 (2015), 478–486.