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Journal of Zhejiang University SCIENCE B 1998 Vol.-1 No.-1 P.

http://doi.org/10.1631/jzus.B2400099


Single-cell transcriptome analysis reveals abnormal angiogenesis and placentation by loss of imprinted glutaminyl-peptide cyclotransferase


Author(s):  Jing GUO, Jihong ZHENG, Ruixia LI, Jindong YAO, He ZHANG, Xu WANG, Chao ZHANG

Affiliation(s):  Fundamental Research Center, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Life Sciences and Technology, Tongji University, Shanghai, China; more

Corresponding email(s):   xzw0070@auburn.edu, zhangchao@tongji.edu.cn

Key Words:  Qpct-/- mice, Placenta, Single cell sequencing, Overgrowth, Angiogenesis


Jing GUO, Jihong ZHENG, Ruixia LI, Jindong YAO, He ZHANG, Xu WANG, Chao ZHANG. Single-cell transcriptome analysis reveals abnormal angiogenesis and placentation by loss of imprinted glutaminyl-peptide cyclotransferase[J]. Journal of Zhejiang University Science B, 1998, -1(-1): .

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%T Single-cell transcriptome analysis reveals abnormal angiogenesis and placentation by loss of imprinted glutaminyl-peptide cyclotransferase
%A Jing GUO
%A Jihong ZHENG
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%A He ZHANG
%A Xu WANG
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%J Journal of Zhejiang University SCIENCE B
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A1 - He ZHANG
A1 - Xu WANG
A1 - Chao ZHANG
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PB - Zhejiang University Press & Springer
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Abstract: 
Imprinted genes play a key role in regulating mammalian placental and embryonic development. Here, we generated Qpct-knockout mice utilizing the Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR/Cas9) platform and identified Qpct as a novel anti-angiogenic factor in regulating mouse placentation. Compared with Qpct+/+ mice, placentae and embryos (Qpct-/+ and Qpct-/-) showed significant overgrowth at E12.5, 15.5, and 18.5. Using single-cell transcriptomic analyses of 32,309 cells from Qpct+/+ and Qpct-/- mouse placentae, we identified 13 cell clusters via snRNA-seq (8,880 Qpct+/+ and 13,577 Qpct-/- cells) and 20 cell clusters via scRNA-seq (6,567 Qpct+/+ and 3,285 Qpct-/- cells). Furthermore, we observed a global upregulation of pro-angiogenic genes in Qpct-/- background. Immunohistochemistry assays revealed a notable increase of blood vessels number in the decidual and labyrinthine layers of E15.5 Qpct-/+ and Qpct-/- mice. Moreover, the elevation of multiple pairs of ligand-receptor interactions were observed in decidual cells, endothelial cells, and macrophages, promoting angiogenesis and inflammatory response. Our findings indicate that loss of maternal Qpct leads to altered phenotypic characteristics of placentae and embryos and promotes angiogenesis in murine placentae.

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