USP22 controls multiple signaling pathways that are essential for vasculature formation in the mouse placenta

Evangelia Koutelou, Li Wang, Andria C. Schibler, Hsueh Ping Chao, Xianghong Kuang, Kevin Lin, Yue Lu, Jianjun Shen, Collene R. Jeter, Andrew Salinger, Marenda Wilson, Yi Chun Chen, Boyko S. Atanassov, Dean G. Tang, Sharon Y.R. Dent

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

USP22, a component of the SAGA complex, is overexpressed in highly aggressive cancers, but the normal functions of this deubiquitinase are not well defined. We determined that loss of USP22 in mice results in embryonic lethality due to defects in extra-embryonic placental tissues and failure to establish proper vascular interactions with the maternal circulatory system. These phenotypes arise from abnormal gene expression patterns that reflect defective kinase signaling, including TGFβ and several receptor tyrosine kinase pathways. USP22 deletion in endothelial cells and pericytes that are induced from embryonic stem cells also hinders these signaling cascades, with detrimental effects on cell survival and differentiation as well as on the ability to form vessels. Our findings provide new insights into the functions of USP22 during development that may offer clues to its role in disease states.

Original languageEnglish (US)
Article numberdev174037
JournalDevelopment (Cambridge)
Volume146
Issue number4
DOIs
StatePublished - Feb 2019

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Pericytes
Receptor Protein-Tyrosine Kinases
Embryonic Stem Cells
Cardiovascular System
Placenta
Blood Vessels
Cell Differentiation
Cell Survival
Phosphotransferases
Endothelial Cells
Mothers
Phenotype
Gene Expression
Neoplasms
Deubiquitinating Enzymes

Keywords

  • Endothelial cells
  • Mouse
  • Pericytes
  • Placenta
  • RTK receptors
  • SAGA
  • TGFβ signaling
  • USP22
  • Vascular development

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

USP22 controls multiple signaling pathways that are essential for vasculature formation in the mouse placenta. / Koutelou, Evangelia; Wang, Li; Schibler, Andria C.; Chao, Hsueh Ping; Kuang, Xianghong; Lin, Kevin; Lu, Yue; Shen, Jianjun; Jeter, Collene R.; Salinger, Andrew; Wilson, Marenda; Chen, Yi Chun; Atanassov, Boyko S.; Tang, Dean G.; Dent, Sharon Y.R.

In: Development (Cambridge), Vol. 146, No. 4, dev174037, 02.2019.

Research output: Contribution to journalArticle

Koutelou, E, Wang, L, Schibler, AC, Chao, HP, Kuang, X, Lin, K, Lu, Y, Shen, J, Jeter, CR, Salinger, A, Wilson, M, Chen, YC, Atanassov, BS, Tang, DG & Dent, SYR 2019, 'USP22 controls multiple signaling pathways that are essential for vasculature formation in the mouse placenta', Development (Cambridge), vol. 146, no. 4, dev174037. https://doi.org/10.1242/dev.174037
Koutelou, Evangelia ; Wang, Li ; Schibler, Andria C. ; Chao, Hsueh Ping ; Kuang, Xianghong ; Lin, Kevin ; Lu, Yue ; Shen, Jianjun ; Jeter, Collene R. ; Salinger, Andrew ; Wilson, Marenda ; Chen, Yi Chun ; Atanassov, Boyko S. ; Tang, Dean G. ; Dent, Sharon Y.R. / USP22 controls multiple signaling pathways that are essential for vasculature formation in the mouse placenta. In: Development (Cambridge). 2019 ; Vol. 146, No. 4.
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