Single-nucleus multi-omics dissection of dysregulated trophoblast development and disrupted immune microenvironment in complete hydatidiform moles - PubMed
5 hours ago
- #trophoblast-development
- #multi-omics
- #hydatidiform-mole
- Hydatidiform mole (HM) is characterized by aberrant trophoblast proliferation, leading to pregnancy loss and increased risk of malignancy.
- Single-nucleus multi-omics (snRNA-seq, snATAC-seq, and spatial transcriptomics) was used to analyze androgenetic complete HM compared to controls.
- Three major trophoblast lineages (VCT, SCT, EVT) show distinct differentiation and functional associations in HM.
- Imprinted genes exhibit cell-type-specific dysregulation, particularly in trophoblasts.
- Deficiency of progenitor subpopulation VCT1 and inactivation of TP63 were observed in HM.
- EVT in HM showed enhanced invasive/migratory capacity and hyperactivation of MYCN.
- SCT-Mature1 compartment displayed impaired maturation and downregulation of placenta-specific hormones (PSG, CSH, PAPPA).
- RASA1 was identified as a novel key regulator with low expression in HM, affecting SCT differentiation.
- Potential therapeutic targets include MYCN and RASA1; diagnostic utility of hormone monitoring is suggested.