JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

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

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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,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2400099

@article{title="Single-cell transcriptome analysis reveals abnormal angiogenesis and placentation by loss of imprinted glutaminyl-peptide cyclotransferase",
author="Jing GUO, Jihong ZHENG, Ruixia LI, Jindong YAO, He ZHANG, Xu WANG, Chao ZHANG",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2400099"
}

%0 Journal Article
%T Single-cell transcriptome analysis reveals abnormal angiogenesis and placentation by loss of imprinted glutaminyl-peptide cyclotransferase
%A Jing GUO
%A Jihong ZHENG
%A Ruixia LI
%A Jindong YAO
%A He ZHANG
%A Xu WANG
%A Chao ZHANG
%J Journal of Zhejiang University SCIENCE B
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%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2400099"

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T1 - Single-cell transcriptome analysis reveals abnormal angiogenesis and placentation by loss of imprinted glutaminyl-peptide cyclotransferase
A1 - Jing GUO
A1 - Jihong ZHENG
A1 - Ruixia LI
A1 - Jindong YAO
A1 - He ZHANG
A1 - Xu WANG
A1 - Chao ZHANG
J0 - Journal of Zhejiang University Science B
SP -
EP -
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
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doi="https://doi.org/10.1631/jzus.B2400099"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

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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