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Phosphorylation dynamics during early differentiation of human embryonic stem cells

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Dennis Van Hoof
  • Javier Muñoz
  • Stefan R Braam
  • Martijn W H Pinkse
  • Rune Linding
  • Albert J R Heck
  • Christine L Mummery
  • Jeroen Krijgsveld

Pluripotent stem cells self-renew indefinitely and possess characteristic protein-protein networks that remodel during differentiation. How this occurs is poorly understood. Using quantitative mass spectrometry, we analyzed the (phospho)proteome of human embryonic stem cells (hESCs) during differentiation induced by bone morphogenetic protein (BMP) and removal of hESC growth factors. Of 5222 proteins identified, 1399 were phosphorylated on 3067 residues. Approximately 50% of these phosphosites were regulated within 1 hr of differentiation induction, revealing a complex interplay of phosphorylation networks spanning different signaling pathways and kinase activities. Among the phosphorylated proteins was the pluripotency-associated protein SOX2, which was SUMOylated as a result of phosphorylation. Using the data to predict kinase-substrate relationships, we reconstructed the hESC kinome; CDK1/2 emerged as central in controlling self-renewal and lineage specification. The findings provide new insights into how hESCs exit the pluripotent state and present the hESC (phospho)proteome resource as a complement to existing pluripotency network databases.

OriginalsprogEngelsk
TidsskriftCell Stem Cell
Vol/bind5
Udgave nummer2
Sider (fra-til)214-226
Antal sider13
DOI
StatusUdgivet - 7 aug. 2009
Eksternt udgivetJa

ID: 122677541