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NLRP7 maintains the genomic stability during early human embryogenesis via mediating alternative splicing

ABSTRACT: Genomic instability is the main cause of abnormal embryo development and abortion. NLRP7 dysfunctions affect embryonic development and lead to recurrent pregnancy loss (RPL) or hydatidiform moles (HM), but the underlying mechanisms remain largely elusive. In this study, we found that NLRP7 knockout affected the genetic stability, resulting in increased DNA damage in both human embryonic stem cells (hESCs) and blastoids, making embryonic cells in blastoids more susceptible to apoptosis. Mechanistically, NLRP7 could interact with factors related to alternative splicing (AS) and DNA damage response (DDR), including DDX39B, PRPF8, THRAP3 and PARP1, and its dysfunction led to abnormal AS of genes involved in Homologous recombination (HR) in hESCs, indicating that NLRP7-mediated AS is required for the maintenance of genome integrity during early human embryogenesis. Together, this study first uncovers that NLRP7 plays an essential role in the maintenance of genetic stability during early human embryonic development by regulating AS of HR-related genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281755 | GEO | 2025/01/16

REPOSITORIES: GEO

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human Embryonic stem cells LC-MSMS

Project description:Genomic instability is the main cause of abnormal embryo development and abortion. NLRP7 dysfunctions affect embryonic development and lead to Hydatidiform Moles, but the underlying mechanisms remain largely elusive. Here, we show that NLRP7 knockout affects the genetic stability, resulting in increased DNA damage in both human embryonic stem cells and blastoids, making embryonic cells in blastoids more susceptible to apoptosis. Mechanistically, NLRP7 can interact with factors related to alternative splicing and DNA damage response, including DDX39B, PRPF8, THRAP3 and PARP1. Moreover, NLRP7 dysfunction leads to abnormal AS of genes involved in Homologous recombination in human embryonic stem cells, Such as Brca1 and Rad51. These results indicate that NLRP7-mediated Alternative splicing is potentially required for the maintenance of genome integrity during early human embryogenesis. Together, this study uncovers that NLRP7 plays an essential role in the maintenance of genetic stability during early human embryonic development by regulating alternative splicing of Homologous Recombination-related genes.

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A Patient specific iPSC-based model of Hydatidiform mole reveals abnormal BMP4 signaling caused by NLRP7 deficiency

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Project description:A Patient specific iPSC-based model of Hydatidiform mole reveals abnormal BMP4 signaling caused by NLRP7 deficiency

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NLRP7 maintains the genomic stability during early human embryogenesis via mediating alternative splicing

Project description:NLRP7 maintains the genomic stability during early human embryogenesis via mediating alternative splicing

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Methylation profiling of molar tissues caused by recessive maternal-effect NLRP7 mutations

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