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PreprintCited by 146Pluripotent Stem Cells ResearchDevelopmental Biology and Gene RegulationEpigenetics and DNA Methylation

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Multi-Omic Profiling Reveals Dynamics of the Phased Progression of Pluripotency

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Yang, Pengyi, Humphrey, Sean J., Cinghu, Senthilkumar, Pathania, Rajneesh, Oldfield, Andrew J., Kumar, Dhirendra, Perera, Dinuka, Yang, Jean Y.H., James, David E., Mann, Matthias, Jothi, Raja·2018·Cell Systems
DOI 10.1101/415430PMC PMC6544180

Preprint — published as 10.1016/j.cels.2019.03.012 · Paper page

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Abstract

SUMMARY: Pluripotency is highly dynamic and progresses through a continuum of pluripotent stem-cell states. The two states that bookend the pluripotency continuum, naïve and primed, are well characterized, but our understanding of the intermediate states and transitions between them remain incomplete. Here, we dissect the dynamics of pluripotent state transitions underlying pre-to post-implantation epiblast differentiation. Through comprehensive mapping of the proteome, phosphoproteome, transcriptome, and epigenome of mouse embryonic stem cells transitioning from naïve to primed pluripotency, we find that rapid, acute, and widespread changes to the phosphoproteome precede ordered changes to the epigenome, transcriptome, and proteome. Reconstruction of kinase-substrate networks reveals signaling cascades, dynamics, and crosstalk. Distinct waves of global proteomic changes demarcate discrete phases of pluripotency, characterized by cell-state-specific surface marker expression. Our data provide new insights into the multi-layered control of the phased progression of pluripotency and a foundation for modeling mechanisms underlying pre-to post-implantation epiblast differentiation. HIGHLIGHTS: Multi-ome maps of cells transitioning from naïve to primed pluripotency Phosphoproteome dynamics precede changes to epigenome, transcriptome, and proteome Kinase-substrate network reconstruction uncovers signaling dynamics and crosstalk Proteins and cell surface markers that track pluripotent state transitions Comparative analysis of mouse and human pluripotent states

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Cites

  • Global quantification of mammalian gene expression control

    Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · cited 2×

    “In agreement with previous studies, which have found a generally limited correlation between steady-state mRNA and protein levels in mammalian systems (Schwanhausser et al., 2011), we found correlation between these layers to be rather moderate and stable across all time-points (Pearson, R = 0.”
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Flagged first, then by citations

Research works printed but not linked: 119

  1. 10.1038/nature19949 · DOI · Paper page
  2. 10.1038/nrg3356 · DOI
  3. 10.1016/j.cell.2013.03.012 · DOI
  4. 10.1038/ncb2965 · DOI
  5. 10.1016/j.devcel.2015.10.011 · DOI
  6. 10.1016/j.stem.2009.06.002 · DOI
  7. 10.1038/nature05950 · DOI
  8. 10.1016/j.stem.2014.04.003 · DOI · Paper page
  9. 10.1038/nature20578 · DOI · Paper page
  10. 10.1016/j.cell.2015.06.016 · DOI
  11. 10.1111/j.1742-4658.2012.08716.x · DOI · Paper page
  12. 10.1016/j.stem.2013.11.015 · DOI
  13. Chen, A.F. , Liu, A.J. , Krishnakumar, R. , Freimer, J.W. , DeVeale, B. , and Blelloch, R. (2018). GRHL2-Dependent Enhancer Switching Maintains a Pluripotent Stem Cell Transcriptional Subnetwork after Exit from Naive Pluripotency. Cell Stem Cell. · DOI
  14. 10.1038/nature23274 · DOI
  15. 10.1038/ncomms9992 · DOI
  16. 10.1016/j.cell.2016.12.016 · DOI · Paper page
  17. 10.1038/nmeth1109-786 · DOI
  18. 10.1016/j.stem.2017.02.014 · DOI
  19. 10.1038/nbt.1511 · DOI · Paper page
  20. 10.1242/dev.116061 · DOI
  21. 10.1038/nature15515 · DOI
  22. 10.1039/B908315D · DOI · Paper page
  23. 10.1146/annurev-biochem-052709-104948 · DOI
  24. 10.1101/gad.1463706 · DOI
  25. 10.1016/j.stem.2014.05.005 · DOI
  26. 10.1038/ncomms12589 · DOI
  27. 10.1038/nature12745 · DOI
  28. 10.1093/nar/gku1071 · DOI
  29. 10.1016/j.stem.2014.09.015 · DOI
  30. 10.1016/j.cell.2010.10.015 · DOI
  31. 10.1016/j.cell.2011.06.052 · DOI
  32. 10.1093/nar/gkr1122 · DOI
  33. 10.1016/j.stem.2014.09.014 · DOI
  34. 10.1016/j.celrep.2012.10.022 · DOI
  35. 10.1038/nbt.3327 · DOI
  36. 10.1242/dev.142711 · DOI
  37. 10.1016/j.stem.2013.09.014 · DOI
  38. 10.1038/nmeth.2834 · DOI · Paper page
  39. 10.1242/dev.02880 · DOI
  40. 10.1016/j.stem.2015.03.002 · DOI
  41. 10.1007/s00018-016-2297-8 · DOI · Paper page
  42. 10.1242/dev.050146 · DOI
  43. Li, Q.R. , Xing, X.B. , Chen, T.T. , Li, R.X. , Dai, J. , Sheng, Q.H. , Xin, S.M. , Zhu, L.L. , Jin, Y. , Pei, G. , et al. (2011). Large scale phosphoproteome profiles comprehensive features of mouse embryonic stem cells. Mol Cell Proteomics 10, M110 001750. · DOI
  44. 10.1016/j.cell.2012.03.026 · DOI
  45. 10.1016/j.tibs.2011.03.006 · DOI · Paper page
  46. 10.1002/pmic.200400990 · DOI
  47. Nett, I.R. , Mulas, C. , Gatto, L. , Lilley, K.S. , and Smith, A. (2018). Negative feedback via RSK modulates Erk-dependent progression from naive pluripotency. EMBO Rep. · DOI
  48. 10.1016/j.stem.2009.05.015 · DOI
  49. 10.1038/nature08113 · DOI · Paper page
  50. 10.1002/wdev.176 · DOI · Paper page
  51. 10.1016/j.stem.2016.01.019 · DOI
  52. 10.1128/MCB.05258-11 · DOI
  53. 10.1016/j.cell.2012.11.039 · DOI · Paper page
  54. 10.1126/scisignal.2001570 · DOI · Paper page
  55. 10.1021/acs.analchem.5b04123 · DOI · Paper page
  56. 10.1016/j.cmet.2016.10.004 · DOI
  57. 10.1016/j.stem.2016.12.004 · DOI
  58. Schwarz, B.A. , Cetinbas, M. , Clement, K. , Walsh, R.M. , Cheloufi, S. , Gu, H. , Langkabel, J. , Kamiya, A. , Schorle, H. , Meissner, A. , et al. (2018). Prospective Isolation of Poised iPSC Intermediates Reveals Principles of Cellular Reprogramming. Cell Stem Cell. · DOI · Paper page
  59. 10.1038/nature24675 · DOI
  60. 10.1016/j.celrep.2014.07.036 · DOI
  61. 10.1016/j.devcel.2016.08.008 · DOI
  62. 10.1242/dev.142679 · DOI
  63. 10.1038/nature10960 · DOI
  64. 10.1073/pnas.0811964106 · DOI
  65. 10.1038/emboj.2008.192 · DOI
  66. 10.1016/j.cell.2014.08.029 · DOI
  67. 10.1038/nature05972 · DOI
  68. 10.1016/j.stem.2014.07.002 · DOI
  69. 2017, LIN28 phosphorylation by MAPK/ERK couples signalling to the post-transcriptional control of pluripotency, Nat Cell Biol, 19, 60, 10.1038/ncb3453 · DOI
  70. 10.1038/nprot.2016.136 · DOI
  71. 10.1016/j.stem.2009.05.021 · DOI
  72. 10.1089/scd.2013.0639 · DOI
  73. 10.1073/pnas.1319738111 · DOI
  74. 10.1038/nrm.2015.28 · DOI · Paper page
  75. 10.1021/pr900748n · DOI · Paper page
  76. 10.1016/j.stem.2015.10.009 · DOI
  77. 10.1038/ng.186 · DOI
  78. 10.1016/j.stem.2012.12.012 · DOI
  79. 10.1038/nsmb.2660 · DOI · Paper page
  80. 10.1093/bioinformatics/btv550 · DOI
  81. 2016, KinasePA: Phosphoproteomics data annotation using hypothesis driven kinase perturbation analysis, Proteomics, 16, 1868, 10.1002/pmic.201600068 · DOI
  82. 10.1371/journal.pcbi.1004403 · DOI
  83. 10.1038/nature06968 · DOI · Paper page
  84. 10.1242/dev.137075 · DOI
  85. 10.1093/nar/gkr965 · DOI
  86. 10.1093/bioinformatics/btu638 · DOI · Paper page
  87. 10.1016/j.devcel.2015.10.011 · DOI
  88. 10.1016/j.stem.2013.11.015 · DOI
  89. 10.1038/nmeth1109-786 · DOI
  90. 10.1038/nbt.1511 · DOI · Paper page
  91. 10.1093/nar/gkw936 · DOI
  92. 10.1093/bioinformatics/bts635 · DOI · Paper page
  93. 10.1093/bioinformatics/bti525 · DOI
  94. 10.1016/j.stem.2014.05.005 · DOI
  95. 10.1038/ncomms12589 · DOI
  96. 10.1093/nar/gkr991 · DOI
  97. 10.1093/nar/gku1179 · DOI · Paper page
  98. 10.1016/j.cell.2011.06.052 · DOI
  99. 10.1016/S0092-8674(01)00598-0 · DOI
  100. 10.1093/nar/gkr1122 · DOI
  101. 10.1038/nbt.3327 · DOI
  102. 10.1093/biostatistics/kxj037 · DOI · Paper page
  103. 10.1242/dev.142711 · DOI
  104. 10.1038/nmeth.2834 · DOI · Paper page
  105. 10.1186/gb-2009-10-3-r25 · DOI · Paper page
  106. 10.1186/s13059-014-0550-8 · DOI · Paper page
  107. 10.1016/j.molcel.2014.07.005 · DOI
  108. 10.1002/0471250953.bi1112s47 · DOI
  109. 10.1093/nar/gkv007 · DOI · Paper page
  110. 10.1093/bioinformatics/btp616 · DOI · Paper page
  111. 10.1016/j.cmet.2016.10.004 · DOI
  112. 10.1016/j.cell.2014.08.029 · DOI
  113. 10.1073/pnas.091062498 · DOI · Paper page
  114. 10.1021/pr900748n · DOI · Paper page
  115. 10.1038/nsmb.2660 · DOI · Paper page
  116. 10.1093/bioinformatics/btv550 · DOI
  117. 2016, KinasePA: Phosphoproteomics data annotation using hypothesis driven kinase perturbation analysis, Proteomics, 16, 1868, 10.1002/pmic.201600068 · DOI
  118. 10.1093/bioinformatics/btt616 · DOI
  119. 10.1371/journal.pcbi.1004403 · DOI

Metadata

Authors
Yang, P., Humphrey, S. J., Cinghu, S., Pathania, R., Oldfield, A. J., Kumar, D., Perera, D., Yang, J. Y. H., James, D. E., Mann, M., & Jothi, R.
Affiliations
  • The University of Sydney (AU)
  • National Institutes of Health (US)
  • Max Planck Institute of Biochemistry (DE)
Corresponding author
  • Yang, Pengyi
  • Humphrey, Sean J.
  • Jothi, Raja
ORCID
Venue
Cell Systems
Publisher
openRxiv
Published
2018-09-12
Volume
8
Issue
5
Pages
427-445.e10
ISSN
2405-4712 (ISSN-L)
DOI
10.1101/415430
PMC
PMC6544180
OpenAlex
W2950402574
Cited by
146
References
1
Citations by year
2026: 6 · 2025: 21 · 2024: 14 · 2023: 28 · 2022: 25 · 2021: 26 · 2020: 20 · 2019: 6
FWCI
6.37
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Cell Systems (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion, cc-by-nc-nd)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
Funders
  • European Molecular Biology Organization
  • Max-Planck-Gesellschaft
  • National Institutes of Health (1Z1AES102625)
  • Australian Research Council
  • Max Planck Institute for Dynamics of Complex Technical Systems Magdeburg
  • National Institute of Environmental Health Sciences (ZIAES102625)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
pluripotency, naive pluripotency, primed pluripotency, embryonic stem cells, phosphoproteome, proteome, transcriptome, epigenome, signaling pathways
MeSH terms
Epigenome, Animals, Cell Differentiation, Germ Layers, Humans, Signal Transduction, Gene Expression Regulation, Developmental, Cell Lineage, Proteome, Pluripotent Stem Cells, Embryonic Stem Cells, Transcriptome

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