De Novo Germline and Somatic Variants Convergently Promote Endothelial-to-Mesenchymal Transition in Simplex Brain Arteriovenous Malformation

Hao Li; Yoonhee Nam; Ran Huo; Weilun Fu; Biaobin Jiang; Qiuxia Zhou; Dong Song; Yingxi Yang; Yuming Jiao; Jiancong Weng; Zihan Yan; Lin Di; Jie Li; Jie Wang; Hongyuan Xu; Shuo Wang; Jizong Zhao; Zilong Wen; Jiguang Wang; Yong Cao

doi:10.1161/CIRCRESAHA.121.319004

De Novo Germline and Somatic Variants Convergently Promote Endothelial-to-Mesenchymal Transition in Simplex Brain Arteriovenous Malformation

Circ Res. 2021 Oct 15;129(9):825-839. doi: 10.1161/CIRCRESAHA.121.319004. Epub 2021 Sep 17.

Authors

Hao Li^#^{1

2}, Yoonhee Nam^#³, Ran Huo^#^{1

2}, Weilun Fu^#^{1

2}, Biaobin Jiang^{4

5}, Qiuxia Zhou³, Dong Song³, Yingxi Yang^{4

5}, Yuming Jiao^{1

2}, Jiancong Weng^{1

2}, Zihan Yan^{1

2}, Lin Di^{6

7}, Jie Li⁸, Jie Wang^{1

2}, Hongyuan Xu^{1

2}, Shuo Wang^{1

2}, Jizong Zhao^{1

2}, Zilong Wen^{3

9}, Jiguang Wang^{3

4

10}, Yong Cao^{1

11

2}

Affiliations

¹ Neurosurgery, Beijing Tiantan Hospital (H.L., R.H., W.F., Y.J., Jiancong Weng, Z.Y., Jie Wang, H.X., S.W., J.Z., Y.C.), Capital Medical University, China.
² China National Clinical Research Center for Neurological Diseases, Beijing, China (H.L., R.H., W.F., Y.J., Jiancong Weng, Z.Y., Jie Wang, H.X., S.W., J.Z., Y.C.).
³ Division of Life Science, State Key Laboratory of Molecular Neuroscience (Y.N., Q.Z., D.S., Z.W., Jiguang Wang), Clear Water Bay, Kowloon, Hong Kong SAR, China.
⁴ Chemical and Biological Engineering (B.J., Y.Y., Jiguang Wang), Clear Water Bay, Kowloon, Hong Kong SAR, China.
⁵ the Hong Kong University of Science and Technology (B.J.,Y.Y.), Clear Water Bay, Kowloon, Hong Kong SAR, China.
⁶ Beijing Advanced Innovation Center for Genomics, Biomedical Pioneering Innovation Center, Peking-Tsinghua Center for Life Sciences (L.D.), Peking University, Beijing, China.
⁷ School of Life Sciences (L.D.), Peking University, Beijing, China.
⁸ School of Life Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China (J.L.).
⁹ Greater Bay Biomedical Innocenter, Shenzhen Bay Laboratory, Shenzhen, China (Z.W.).
¹⁰ Hong Kong Center for Neurodegenerative Diseases, Hong Kong Science Park, Hong Kong SAR, China (Jiguang Wang).
¹¹ Beijing Neurosurgical Institute (Y.C.), Capital Medical University, China.

^# Contributed equally.

PMID: 34530633
DOI: 10.1161/CIRCRESAHA.121.319004

Abstract

[Figure: see text].

Keywords: computational biology; germ-line mutation; high-throughput nucleotide sequencing; intracranial arteriovenous malformations.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Animals
Arteriovenous Malformations / genetics*
Arteriovenous Malformations / metabolism
Arteriovenous Malformations / pathology
Basic Helix-Loop-Helix Transcription Factors / genetics
Cell Movement
Cells, Cultured
Endoglin / genetics
Endothelium, Vascular / metabolism
Endothelium, Vascular / pathology
Epithelial-Mesenchymal Transition*
Germ-Line Mutation*
Human Umbilical Vein Endothelial Cells / metabolism
Humans
Neovascularization, Physiologic
Proto-Oncogene Proteins p21(ras) / genetics
Zebrafish

Substances

Adaptor Proteins, Signal Transducing
Basic Helix-Loop-Helix Transcription Factors
ENG protein, human
EXPH5 protein, human
Endoglin
KRAS protein, human
endothelial PAS domain-containing protein 1
Proto-Oncogene Proteins p21(ras)