Cell-cell communication-mediated cell-type-specific parent-of-origin effects in mammals

Abstract Genomic imprinting is manifested as monoallelic expression of genes according to parental origin, which is closely linked to mammalian placentation and human diseases. Yet, it is unclear how genomic imprinting evolves in different cell types. Here we generate a single-nucleus transcriptomic...

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Main Authors: Jia-Jin Wu, Enqin Zheng, Langqing Liu, Jianping Quan, Donglin Ruan, Zekai Yao, Jifei Yang, Xuehua Li, Shiyuan Wang, Ming Yang, Zebin Zhang, Meng Lin, Zheng Xu, Zicong Li, Gengyuan Cai, Jie Yang, Zhenfang Wu
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60469-y
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author Jia-Jin Wu
Enqin Zheng
Langqing Liu
Jianping Quan
Donglin Ruan
Zekai Yao
Jifei Yang
Xuehua Li
Shiyuan Wang
Ming Yang
Zebin Zhang
Meng Lin
Zheng Xu
Zicong Li
Gengyuan Cai
Jie Yang
Zhenfang Wu
author_facet Jia-Jin Wu
Enqin Zheng
Langqing Liu
Jianping Quan
Donglin Ruan
Zekai Yao
Jifei Yang
Xuehua Li
Shiyuan Wang
Ming Yang
Zebin Zhang
Meng Lin
Zheng Xu
Zicong Li
Gengyuan Cai
Jie Yang
Zhenfang Wu
author_sort Jia-Jin Wu
collection DOAJ
description Abstract Genomic imprinting is manifested as monoallelic expression of genes according to parental origin, which is closely linked to mammalian placentation and human diseases. Yet, it is unclear how genomic imprinting evolves in different cell types. Here we generate a single-nucleus transcriptomic landscape of mammalian placental development, identifying 5 major cell types and 14 trophoblast subtypes. By developing a framework for integrating the datasets of single-nucleus transcriptome and whole-genome variations from reciprocal crosses of the genetically distinct Duroc and Lulai pig breeds, we construct a cell-type-specific genomic imprinting landscape, uncovering 118 candidate imprinted genes. We expand the mammalian imprinting gene catalog by identifying 97 previously uncharacterized imprinted candidates. Nearly 75% of imprinted candidates exhibit a cell-type- and developmental-stage-dependent manner. Through cross-species analysis, we show that cell-cell communication, especially the integration and modification of signaling pathways into a cell-type-specific autocrine network, drives biased allelic expression of imprinted genes in pigs, mice, and humans. Our findings provide genetic and molecular insights into parent-of-origin effects on gene expression, offering an in-depth understanding of genomic imprinting in mammals.
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spelling doaj-art-9ebe927fa9964af9b40fe5b27e4fd9482025-08-20T02:30:42ZengNature PortfolioNature Communications2041-17232025-06-0116111710.1038/s41467-025-60469-yCell-cell communication-mediated cell-type-specific parent-of-origin effects in mammalsJia-Jin Wu0Enqin Zheng1Langqing Liu2Jianping Quan3Donglin Ruan4Zekai Yao5Jifei Yang6Xuehua Li7Shiyuan Wang8Ming Yang9Zebin Zhang10Meng Lin11Zheng Xu12Zicong Li13Gengyuan Cai14Jie Yang15Zhenfang Wu16State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory for Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, and College of Animal Science, South China Agricultural UniversityState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory for Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, and College of Animal Science, South China Agricultural UniversityState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory for Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, and College of Animal Science, South China Agricultural UniversityState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory for Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, and College of Animal Science, South China Agricultural UniversityState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory for Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, and College of Animal Science, South China Agricultural UniversityState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory for Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, and College of Animal Science, South China Agricultural UniversityState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory for Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, and College of Animal Science, South China Agricultural UniversityState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory for Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, and College of Animal Science, South China Agricultural UniversityState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory for Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, and College of Animal Science, South China Agricultural UniversityZhongkai University of Agriculture and EngineeringState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory for Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, and College of Animal Science, South China Agricultural UniversityState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory for Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, and College of Animal Science, South China Agricultural UniversityState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory for Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, and College of Animal Science, South China Agricultural UniversityState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory for Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, and College of Animal Science, South China Agricultural UniversityState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory for Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, and College of Animal Science, South China Agricultural UniversityState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory for Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, and College of Animal Science, South China Agricultural UniversityState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory for Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, and College of Animal Science, South China Agricultural UniversityAbstract Genomic imprinting is manifested as monoallelic expression of genes according to parental origin, which is closely linked to mammalian placentation and human diseases. Yet, it is unclear how genomic imprinting evolves in different cell types. Here we generate a single-nucleus transcriptomic landscape of mammalian placental development, identifying 5 major cell types and 14 trophoblast subtypes. By developing a framework for integrating the datasets of single-nucleus transcriptome and whole-genome variations from reciprocal crosses of the genetically distinct Duroc and Lulai pig breeds, we construct a cell-type-specific genomic imprinting landscape, uncovering 118 candidate imprinted genes. We expand the mammalian imprinting gene catalog by identifying 97 previously uncharacterized imprinted candidates. Nearly 75% of imprinted candidates exhibit a cell-type- and developmental-stage-dependent manner. Through cross-species analysis, we show that cell-cell communication, especially the integration and modification of signaling pathways into a cell-type-specific autocrine network, drives biased allelic expression of imprinted genes in pigs, mice, and humans. Our findings provide genetic and molecular insights into parent-of-origin effects on gene expression, offering an in-depth understanding of genomic imprinting in mammals.https://doi.org/10.1038/s41467-025-60469-y
spellingShingle Jia-Jin Wu
Enqin Zheng
Langqing Liu
Jianping Quan
Donglin Ruan
Zekai Yao
Jifei Yang
Xuehua Li
Shiyuan Wang
Ming Yang
Zebin Zhang
Meng Lin
Zheng Xu
Zicong Li
Gengyuan Cai
Jie Yang
Zhenfang Wu
Cell-cell communication-mediated cell-type-specific parent-of-origin effects in mammals
Nature Communications
title Cell-cell communication-mediated cell-type-specific parent-of-origin effects in mammals
title_full Cell-cell communication-mediated cell-type-specific parent-of-origin effects in mammals
title_fullStr Cell-cell communication-mediated cell-type-specific parent-of-origin effects in mammals
title_full_unstemmed Cell-cell communication-mediated cell-type-specific parent-of-origin effects in mammals
title_short Cell-cell communication-mediated cell-type-specific parent-of-origin effects in mammals
title_sort cell cell communication mediated cell type specific parent of origin effects in mammals
url https://doi.org/10.1038/s41467-025-60469-y
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