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

Development. 2019 Feb 22;146(4):dev174037. doi: 10.1242/dev.174037. | PubMed

Evangelia Koutelou^1,2,3, Li Wang^4,2,3,5,6, Andria C Schibler^4,2,3,6,7, Hsueh-Ping Chao^4,2,3,5,6, Xianghong Kuang^4,2,3, Kevin Lin^4,2,3, Yue Lu^4,2,3, Jianjun Shen^4,2,3,6, Collene R Jeter^4,2,3, Andrew Salinger^4,2,3, Marenda Wilson⁸, Yi Chun Chen^6,7,8, Boyko S Atanassov^4,2,3, Dean G Tang^4,2,3, Sharon Y R Dent^1,2,3,6

1. Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA ekoutelou@mdanderson.org sroth@mdanderson.org.
2. Center for Cancer Epigenetics, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
3. The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
4. Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
5. Program in Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
6. MD Anderson UTHealth Graduate School of Biomedical Sciences, University of Texas, Houston, TX 77030, USA.
7. Program in Genes and Development, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
8. The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

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.

Presented By Evangelia Koutelou