System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation

Kristoffer T G Rigbolt, Tatyana A Prokhorova, Vyacheslav Akimov, Jeanette Henningsen, Pia Thermann Johansen, Irina Kratchmarova, Moustapha Kassem, Matthias Mann, Jesper V Olsen, Blagoy Blagoev

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

To elucidate cellular events underlying the pluripotency of human embryonic stem cells (hESCs), we performed parallel quantitative proteomic and phosphoproteomic analyses of hESCs during differentiation initiated by a diacylglycerol analog or transfer to media that had not been conditioned by feeder cells. We profiled 6521 proteins and 23,522 phosphorylation sites, of which almost 50% displayed dynamic changes in phosphorylation status during 24 hours of differentiation. These data are a resource for studies of the events associated with the maintenance of hESC pluripotency and those accompanying their differentiation. From these data, we identified a core hESC phosphoproteome of sites with similar robust changes in response to the two distinct treatments. These sites exhibited distinct dynamic phosphorylation patterns, which were linked to known or predicted kinases on the basis of the matching sequence motif. In addition to identifying previously unknown phosphorylation sites on factors associated with differentiation, such as kinases and transcription factors, we observed dynamic phosphorylation of DNA methyltransferases (DNMTs). We found a specific interaction of DNMTs during early differentiation with the PAF1 (polymerase-associated factor 1) transcriptional elongation complex, which binds to promoters of the pluripotency and known DNMT target genes encoding OCT4 and NANOG, thereby providing a possible molecular link for the silencing of these genes during differentiation.
OriginalsprogEngelsk
TidsskriftScience Signaling
Vol/bind4
Udgave nummer164
Sider (fra-til)rs3
ISSN1945-0877
DOI
StatusUdgivet - 2011

Fingeraftryk

Phosphorylation
Proteome
Stem cells
Cell Differentiation
Methyltransferases
DNA
Phosphotransferases
Peptide Elongation Factor 1
Feeder Cells
Gene encoding
Diglycerides
Elongation
Transcription Factors
Genes
Maintenance
Human Embryonic Stem Cells
Proteins

Citer dette

Rigbolt, Kristoffer T G ; Prokhorova, Tatyana A ; Akimov, Vyacheslav ; Henningsen, Jeanette ; Johansen, Pia Thermann ; Kratchmarova, Irina ; Kassem, Moustapha ; Mann, Matthias ; Olsen, Jesper V ; Blagoev, Blagoy. / System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. I: Science Signaling. 2011 ; Bind 4, Nr. 164. s. rs3.
@article{50d60150c6d54907a26116a24ceab3ac,
title = "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation",
abstract = "To elucidate cellular events underlying the pluripotency of human embryonic stem cells (hESCs), we performed parallel quantitative proteomic and phosphoproteomic analyses of hESCs during differentiation initiated by a diacylglycerol analog or transfer to media that had not been conditioned by feeder cells. We profiled 6521 proteins and 23,522 phosphorylation sites, of which almost 50{\%} displayed dynamic changes in phosphorylation status during 24 hours of differentiation. These data are a resource for studies of the events associated with the maintenance of hESC pluripotency and those accompanying their differentiation. From these data, we identified a core hESC phosphoproteome of sites with similar robust changes in response to the two distinct treatments. These sites exhibited distinct dynamic phosphorylation patterns, which were linked to known or predicted kinases on the basis of the matching sequence motif. In addition to identifying previously unknown phosphorylation sites on factors associated with differentiation, such as kinases and transcription factors, we observed dynamic phosphorylation of DNA methyltransferases (DNMTs). We found a specific interaction of DNMTs during early differentiation with the PAF1 (polymerase-associated factor 1) transcriptional elongation complex, which binds to promoters of the pluripotency and known DNMT target genes encoding OCT4 and NANOG, thereby providing a possible molecular link for the silencing of these genes during differentiation.",
author = "Rigbolt, {Kristoffer T G} and Prokhorova, {Tatyana A} and Vyacheslav Akimov and Jeanette Henningsen and Johansen, {Pia Thermann} and Irina Kratchmarova and Moustapha Kassem and Matthias Mann and Olsen, {Jesper V} and Blagoy Blagoev",
year = "2011",
doi = "10.1126/scisignal.2001570",
language = "English",
volume = "4",
pages = "rs3",
journal = "Science Signaling",
issn = "1945-0877",
publisher = "American Association for the Advancement of Science",
number = "164",

}

System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. / Rigbolt, Kristoffer T G; Prokhorova, Tatyana A; Akimov, Vyacheslav; Henningsen, Jeanette; Johansen, Pia Thermann; Kratchmarova, Irina; Kassem, Moustapha; Mann, Matthias; Olsen, Jesper V; Blagoev, Blagoy.

I: Science Signaling, Bind 4, Nr. 164, 2011, s. rs3.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation

AU - Rigbolt, Kristoffer T G

AU - Prokhorova, Tatyana A

AU - Akimov, Vyacheslav

AU - Henningsen, Jeanette

AU - Johansen, Pia Thermann

AU - Kratchmarova, Irina

AU - Kassem, Moustapha

AU - Mann, Matthias

AU - Olsen, Jesper V

AU - Blagoev, Blagoy

PY - 2011

Y1 - 2011

N2 - To elucidate cellular events underlying the pluripotency of human embryonic stem cells (hESCs), we performed parallel quantitative proteomic and phosphoproteomic analyses of hESCs during differentiation initiated by a diacylglycerol analog or transfer to media that had not been conditioned by feeder cells. We profiled 6521 proteins and 23,522 phosphorylation sites, of which almost 50% displayed dynamic changes in phosphorylation status during 24 hours of differentiation. These data are a resource for studies of the events associated with the maintenance of hESC pluripotency and those accompanying their differentiation. From these data, we identified a core hESC phosphoproteome of sites with similar robust changes in response to the two distinct treatments. These sites exhibited distinct dynamic phosphorylation patterns, which were linked to known or predicted kinases on the basis of the matching sequence motif. In addition to identifying previously unknown phosphorylation sites on factors associated with differentiation, such as kinases and transcription factors, we observed dynamic phosphorylation of DNA methyltransferases (DNMTs). We found a specific interaction of DNMTs during early differentiation with the PAF1 (polymerase-associated factor 1) transcriptional elongation complex, which binds to promoters of the pluripotency and known DNMT target genes encoding OCT4 and NANOG, thereby providing a possible molecular link for the silencing of these genes during differentiation.

AB - To elucidate cellular events underlying the pluripotency of human embryonic stem cells (hESCs), we performed parallel quantitative proteomic and phosphoproteomic analyses of hESCs during differentiation initiated by a diacylglycerol analog or transfer to media that had not been conditioned by feeder cells. We profiled 6521 proteins and 23,522 phosphorylation sites, of which almost 50% displayed dynamic changes in phosphorylation status during 24 hours of differentiation. These data are a resource for studies of the events associated with the maintenance of hESC pluripotency and those accompanying their differentiation. From these data, we identified a core hESC phosphoproteome of sites with similar robust changes in response to the two distinct treatments. These sites exhibited distinct dynamic phosphorylation patterns, which were linked to known or predicted kinases on the basis of the matching sequence motif. In addition to identifying previously unknown phosphorylation sites on factors associated with differentiation, such as kinases and transcription factors, we observed dynamic phosphorylation of DNA methyltransferases (DNMTs). We found a specific interaction of DNMTs during early differentiation with the PAF1 (polymerase-associated factor 1) transcriptional elongation complex, which binds to promoters of the pluripotency and known DNMT target genes encoding OCT4 and NANOG, thereby providing a possible molecular link for the silencing of these genes during differentiation.

U2 - 10.1126/scisignal.2001570

DO - 10.1126/scisignal.2001570

M3 - Journal article

C2 - 21406692

VL - 4

SP - rs3

JO - Science Signaling

JF - Science Signaling

SN - 1945-0877

IS - 164

ER -