Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells

Nature Communications

Volumn 8, Issue 1, 2017, Pages

  Semrau, Stefan ^a,b,c   Goldmann, Johanna E ^b   Soumillon, Magali ^d,e   Mikkelsen, Tarjei S ^d,e   Jaenisch, Rudolf ^b,f   Van Oudenaarden, Alexander ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^b WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH   (United States)

^c LEIDEN UNIVERSITY   (Netherlands)

^d BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^e Harvard University   (United States)

^f MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

RETINOIC ACID; PROTEIN; TRANSCRIPTOME;

DIFFERENTIATION; GENE; GENE EXPRESSION; RNA;

ANIMAL CELL; ARTICLE; CELL DIFFERENTIATION; CELL LEVEL; CELL LINEAGE; CONTROLLED STUDY; EMBRYO; EMBRYONIC STEM CELL; GENE EXPRESSION; MOUSE; NONHUMAN; TRANSCRIPTOMICS; ANIMAL; CYTOLOGY; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; PLURIPOTENT STEM CELL; SINGLE CELL ANALYSIS;

ANIMALS; CELL DIFFERENTIATION; CELL LINEAGE; EMBRYONIC STEM CELLS; GENE EXPRESSION REGULATION, DEVELOPMENTAL; MICE; PLURIPOTENT STEM CELLS; PROTEINS; SINGLE-CELL ANALYSIS; TRANSCRIPTOME;

EID: 85032197721     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/s41467-017-01076-4     Document Type: Article

References (70)

1. Cohen, D. E. & Melton, D. Turning straw into gold: directing cell fate for regenerative medicine. Nat. Rev. Genet. 12, 243-252 (2011).
2. Soldner, F. & Jaenisch, R. iPSC Disease Modeling. Science 338, 1155-1156 (2012).
3. Tabar, V. & Studer, L. Pluripotent stem cells in regenerative medicine: challenges and recent progress. Nat. Rev. Genet. 15, 82-92 (2014).
4. Semrau, S. & van Oudenaarden, A. Studying lineage decision-making in vitro: emerging concepts and novel tools. Annu. Rev. Cell Dev. Biol. 31, 317-345 (2015).
5. Balázsi, G., van Oudenaarden, A. & Collins, J. J. Cellular decision making and biological noise: from microbes to mammals. Cell 144, 910-925 (2011).
6. Pauklin, S. & Vallier, L. The cell-cycle state of stem cells determines cell fate propensity. Cell 155, 135-147 (2013).
7. Kobayashi, T. et al. The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells. Gene Dev. 23, 1870-1875 (2009).
8. Morgani, S. M. & Brickman, J. M. The molecular underpinnings of totipotency. Philos. Trans. R. Soc. Lond. B. 369, 20130549-20130549 (2014).
9. Gudas, L. J. & Wagner, J. A. Retinoids regulate stem cell differentiation. J. Cell Physiol. 226, 322-330 (2010).
10. Rhinn, M. & Dolle, P. Retinoic acid signalling during development. Development 139, 843-858 (2012).
11. Ying, Q.-L. et al. The ground state of embryonic stem cell self-renewal. Nature 453, 519-523 (2008).
12. Hennig, C. Cluster-wise assessment of cluster stability. Comput. Stat. Data. Anal. 52, 258-271 (2007).
13. Capo-chichi, C. D. et al. Perception of differentiation cues by GATA factors in primitive endoderm lineage determination of mouse embryonic stem cells. Dev. Biol. 286, 574-586 (2005).
14. Bain, G., Ray, W. J., Yao, M. & Gottlieb, D. I. Retinoic acid promotes neural and represses mesodermal gene expression in mouse embryonic stem cells in culture. Biochem. Biophys. Res. Commun. 223, 691-694 (1996).
15. Soumillon, M., Cacchiarelli, D. & Semrau, S. Characterization of directed differentiation by high-Throughput single-cell RNA-Seq. bioRxiv 003236 (2014).
16. Pruszak, J., Ludwig, W., Blak, A., Alavian, K. & Isacson, O. CD15, CD24, and CD29 define a surface biomarker code for neural lineage differentiation of stem cells. Stem Cells 27, 2928-2940 (2009).
17. Artus, J., Panthier, J.-J. & Hadjantonakis, A.-K. A role for PDGF signaling in expansion of the extra-embryonic endoderm lineage of the mouse blastocyst. Development 137, 3361-3372 (2010).
18. van der Maaten, L. & Hinton, G. Visualizing Data using t-SNE. J. Mach. Learn. Res. 9, 2579-2605 (2008).
19. Marks, H. et al. The Transcriptional and Epigenomic Foundations of Ground State Pluripotency. Cell Stem. Cell 149, 590-604 (2012).
20. Trapnell, C. et al. The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells. Nat. Biotechnol. 32, 381-386 (2014).
21. Boroviak, T. et al. Lineage-specific profiling delineates the emergence and progression of naive pluripotency in mammalian embryogenesis. Dev. Cell 35, 366-382 (2015).
22. Boroviak, T., Loos, R., Bertone, P., Smith, A. & Nichols, J. The ability of inner-cell-mass cells to self-renew as embryonic stem cells is acquired following epiblast specification. Nat. Cell Biol. 16, 516-528 (2014).
23. Roost, M. S. et al. KeyGenes, a tool to probe tissue differentiation using a human fetal transcriptional atlas. Stem Cell Reports 4, 1112-1124 (2015).
24. Shakiba, N. et al. CD24 tracks divergent pluripotent states in mouse and human cells. Nat. Commun. 6, 1-11 (2015).
25. Malleshaiah, M. et al. Nac1 coordinates a sub-network of pluripotency factors to regulate embryonic stem cell differentiation. Cell Reports 14, 1181-1194 (2016).
26. Hamilton, W. B. & Brickman, J. M. Erk signaling suppresses embryonic stem cell self-renewal to specify endoderm. Cell Reports 9, 2056-2070 (2014).
27. Schröter, C., Rué, P., Mackenzie, J. P. & Arias, A. M. FGF/MAPK signaling sets the switching threshold of a bistable circuit controlling cell fate decisions in embryonic stem cells. Development 142, 4205-4216 (2015).
28. Kunath, T. et al. FGF stimulation of the Erk1/2 signalling cascade triggers transition of pluripotent embryonic stem cells from self-renewal to lineage commitment. Development 134, 2895-2902 (2007).
29. Ohnishi, Y. et al. Cell-To-cell expression variability followed by signal reinforcement progressively segregates early mouse lineages. Nat. Cell Bio. 16, 27-37 (2014).
30. JOHNSON, A. T. et al. Synthesis and characterization of a highly potent and effective antagonist of retinoic acid receptors. J. Med. Chem. 38, 4764-4767 (1995).
31. Ying, Q.-L., Stavridis, M., Griffiths, D., Li, M. & Smith, A. Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture. Nat. Biotechnol. 21, 183-186 (2003).
32. Huang, S., Guo, Y.-P., May, G. & Enver, T. Bifurcation dynamics in lineage-commitment in bipotent progenitor cells. Dev. Biol. 305, 695-713 (2007).
33. Picelli, S. et al. Smart-seq2 for sensitive full-length transcriptome profiling in single cells. Nat. Methods. 10, 1096-1098 (2013).
34. Liu, A. & Joyner, A. L. EN and GBX2 play essential roles downstream of FGF8 in patterning the mouse mid/hindbrain region. Development 128, 181-191 (2001).
35. Osumi, N., Shinohara, H., Numayama-Tsuruta, K. & Maekawa, M. Concise review: pax6 transcription factor contributes to both embryonic and adult neurogenesis as a multifunctional regulator. Stem Cells 26, 1663-1672 (2008).
36. Lu, R., Yang, A. & Jin, Y. Dual Functions of T-Box 3 (Tbx3) in the control of self-renewal and extraembryonic endoderm differentiation in mouse embryonic stem cells. J. Biol. Chem. 286, 8425-8436 (2011).
37. Arnold, S. J. & Robertson, E. J. Making a commitment: cell lineage allocation and axis patterning in the early mouse embryo. Nat. Rev. Mol. Cell. Biol. 10, 91-103 (2009).
38. Ballim, R. D., Mendelsohn, C., Papaioannou, V. E. & Prince, S. The ulnar-mammary syndrome gene, Tbx3, is a direct target of the retinoic acid signaling pathway, which regulates its expression during mouse limb development. Mol. Biol. Cell. 23, 2362-2372 (2012).
39. Balmer, J. E. Gene expression regulation by retinoic acid. J. Lipid Res. 43, 1773-1808 (2002).
40. Raj, A., van den Bogaard, P., Rifkin, S. A., van Oudenaarden, A. & Tyagi, S. Imaging individual mRNA molecules using multiple singly labeled probes. Nat. Methods. 5, 877-879 (2008).
41. Klein, A. M. et al. Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 161, 1187-1201 (2015).
42. Morgani, S. M. et al. Totipotent embryonic stem cells arise in ground-state culture conditions. Cell Reports 3, 1945-1957 (2013).
43. Saiz, N., Williams, K. M., Seshan, V. E. & Hadjantonakis, A.-K. Asynchronous fate decisions by single cells collectively ensure consistent lineage composition in the mouse blastocyst. Nat. Commun. 7, 13463 (2016).
44. Chazaud, C., Yamanaka, Y., Pawson, T. & Rossant, J. Early lineage segregation between epiblast and primitive endoderm in mouse blastocysts through the Grb2-MAPK pathway. Dev. Cell 10, 615-624 (2006).
45. Yamanaka, Y., Lanner, F. & Rossant, J. FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst. Development 137, 715-724 (2010).
46. Turner, D. A., Trott, J., Hayward, P., Rue, P. & Martinez Arias, A. An interplay between extracellular signalling and the dynamics of the exit from pluripotency drives cell fate decisions in mouse ES cells. Biology Open 3, 614-626 (2014).
47. Nichols, J., Silva, J., Roode, M. & Smith, A. Suppression of Erk signalling promotes ground state pluripotency in the mouse embryo. Development 136, 3215-3222 (2009).
48. Thomson, M. et al. Pluripotency factors in embryonic stem cells regulate differentiation into germ layers. Cell 145, 875-889 (2011).
49. Trott, J. & Martinez Arias, A. Single cell lineage analysis of mouse embryonic stem cells at the exit from pluripotency. Biology Open 2, 1049-1056 (2013).
50. Marco, E. et al. Bifurcation analysis of single-cell gene expression data reveals epigenetic landscape. Proc. Natl Acad. Sci. 111, E5643-E5650 (2014).
51. Dunn, S. J., Martello, G., Yordanov, B., Emmott, S. & Smith, A. G. Defining an essential transcription factor program for naive pluripotency. Science 344, 1156-1160 (2014).
52. Kim, J., Chu, J., Shen, X., Wang, J. & Orkin, S. H. An extended transcriptional network for pluripotency of embryonic stem cells. Cell 132, 1049-1061 (2008).
53. Ivanova, N. et al. Dissecting self-renewal in stem cells with RNA interference. Nature Publishing Group 442, 533-538 (2006).
54. Niwa, H., Ogawa, K., Shimosato, D. & Adachi, K. A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells. Nature 460, 118-122 (2009).
55. Tai, C.-I. & Ying, Q.-L. Gbx2, a LIF/Stat3 target, promotes reprogramming to and retention of the pluripotent ground state. J. Cell Sci. 126, 1093-1098 (2013).
56. Singer, Z. S. et al. Dynamic Heterogeneity and DNA methylation in embryonic stem cells. Mol. Cell 55, 319-331 (2014).
57. Mojtahedi, M. et al. Cell fate decision as high-dimensional critical state transition. PLoS Biol. 14, e2000640 (2016).
58. Richard, A. et al. Single-cell-based analysis highlights a surge in cell-To-cell molecular variability preceding irreversible commitment in a differentiation process. PLoS Biol. 14, e1002585 (2016).
59. Fox, M. H. A model for the computer analysis of synchronous DNA distributions obtained by flow cytometry. Cytometry 1, 71-77 (1980).
60. Picelli, S. et al. Full-length RNA-seq from single cells using Smart-seq2. Nat. Protoc. 9, 171-181 (2014).
61. Trombetta, J. J. et al. Preparation of single-cell RNA-seq libraries for next generation sequencing. Curr. Protoc. Mol. Biol. 107, 4.22.1-4.22.17 (2014).
62. Trapnell, C. et al. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat. Protoc. 7, 562-578 (2012).
63. Huang, D. W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44-57 (2008).
64. Wang, J. et al. Transcriptome analysis of neural progenitor cells by a genetic dual reporter strategy. Stem Cells 29, 1589-1600 (2011).
65. Hagiwara, K. et al. Molecular and cellular features of murine craniofacial and trunk neural crest cells as stem cell-like cells. PLoS. ONE. 9, e84072 (2014).
66. Stumpo, D. J. et al. Deficiency of the placenta-and yolk sac-specific tristetraprolin family member ZFP36L3 identifies likely mRNA targets and an unexpected link to placental iron metabolism. Development 143, 1424-1433 (2016).
67. Julio, M. K.-D. et al. Regulation of extra-embryonic endoderm stem cell differentiation by Nodal and Cripto signaling. Development 138, 3885-3895 (2011).
68. Wang, L., Feng, Z., Wang, X., Wang, X. & Zhang, X. DEGseq: An R package for identifying differentially expressed genes from RNA-seq data. Bioinformatics 26, 136-138 (2010).
69. Semrau, S. et al. FuseFISH: robust detection of transcribed gene fusions in single cells. Cell Reports 6, 18-23 (2014).
70. Buecker, C. et al. Reorganization of enhancer patterns in transition from naive to primed pluripotency. Cell Stem. Cell 14, 838-853 (2014).