气候变化领域集成服务门户(CCPortal): Overexpression of CD47 is associated with brain overgrowth and 16p11.2 deletion syndrome

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DOI	10.1073/pnas.2005483118
	Overexpression of CD47 is associated with brain overgrowth and 16p11.2 deletion syndrome
	Li J.; Brickler T.; Banuelos A.; Marjon K.; Shcherbina A.; Banerjee S.; Bian J.; Narayanan C.; Weissman I.L.; Chetty S.
发表日期	2021
ISSN	00278424
卷号	118 期号:15
英文摘要	Copy number variation (CNV) at the 16p11.2 locus is associated with neuropsychiatric disorders, such as autism spectrum disorder and schizophrenia. CNVs of the 16p gene can manifest in opposing head sizes. Carriers of 16p11.2 deletion tend to have macrocephaly (or brain enlargement), while those with 16p11.2 duplication frequently have microcephaly. Increases in both gray and white matter volume have been observed in brain imaging studies in 16p11.2 deletion carriers with macrocephaly. Here, we use human induced pluripotent stem cells (hiPSCs) derived from controls and subjects with 16p11.2 deletion and 16p11.2 duplication to understand the underlying mechanisms regulating brain overgrowth. To model both gray and white matter, we differentiated patient-derived iPSCs into neural progenitor cells (NPCs) and oligodendrocyte progenitor cells (OPCs). In both NPCs and OPCs, we show that CD47 (a “don't eat me” signal) is overexpressed in the 16p11.2 deletion carriers contributing to reduced phagocytosis both in vitro and in vivo. Furthermore, 16p11.2 deletion NPCs and OPCs up-regulate cell surface expression of calreticulin (a prophagocytic “eat me” signal) and its binding sites, indicating that these cells should be phagocytosed but fail to be eliminated due to elevations in CD47. Treatment of 16p11.2 deletion NPCs and OPCs with an anti-CD47 antibody to block CD47 restores phagocytosis to control levels. While the CD47 pathway is commonly implicated in cancer progression, we document a role for CD47 in psychiatric disorders associated with brain overgrowth. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	16p11.2 deletion; CD47; IPSCS; Macrocephaly
语种	英语
scopus关键词	calreticulin; CD47 antigen; monoclonal antibody; oligodendrocyte transcription factor 2; receptor type tyrosine protein phosphatase C; transcription factor Nkx2.2; transcription factor Sox10; Article; binding site; cell differentiation; cell surface; chromosome 16p; chromosome deletion; chromosome deletion 16p; chromosome duplication; controlled study; disease association; gene overexpression; gray matter; human; human cell; in vitro study; in vivo study; induced pluripotent stem cell; macrocephaly; mental disease; neural stem cell; oligodendrocyte precursor cell; pathogenesis; phagocytosis; priority journal; protein expression; signal transduction; upregulation; white matter
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179922
作者单位	Department of Psychiatry and Behavioral Sciences, Stanford University, School of Medicine, Stanford, CA 94305, United States; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, School of Medicine, Stanford, CA 94305, United States; Ludwig Center for Cancer Stem Cell Research and Medicine at Stanford, Stanford University, School of Medicine, Stanford, CA 94305, United States; Stanford Cancer Institute, Stanford University, Stanford, CA 94305, United States; Department of Biomedical Informatics, Stanford University, Stanford, CA 94305, United States; Department of Pathology, Stanford University, Stanford, CA 94305, United States
推荐引用方式 GB/T 7714	Li J.,Brickler T.,Banuelos A.,et al. Overexpression of CD47 is associated with brain overgrowth and 16p11.2 deletion syndrome[J],2021,118(15).
APA	Li J..,Brickler T..,Banuelos A..,Marjon K..,Shcherbina A..,...&Chetty S..(2021).Overexpression of CD47 is associated with brain overgrowth and 16p11.2 deletion syndrome.Proceedings of the National Academy of Sciences of the United States of America,118(15).
MLA	Li J.,et al."Overexpression of CD47 is associated with brain overgrowth and 16p11.2 deletion syndrome".Proceedings of the National Academy of Sciences of the United States of America 118.15(2021).