A Simple Human Embryo Model Reveals V-ATPase Requirement in Mammalian Blastocyst Cavitation

ABSTRACT: Human naïve pluripotent stem cells (nPSCs) can differentiate into trophectoderm (TE) and self-organize into embryo-like structures known as blastoids, typically requiring complex cocktails of signaling factors. Here, we demonstrate that dimethyl sulfoxide (DMSO) alone robustly induces TE differentiation and blastoid formation, recapitulating peri-implantation development, including amniotic cavity formation. Using this simplified system, we uncover that lysosomal pathways—particularly those involving the proton pump V-ATPase—are essential for blastoid cavitation. DMSO upregulates key V-ATPase subunits (ATP6V0A4 and ATP6V1B1), which are also upregulated in human embryo TE. Inhibition of V-ATPase in the DMSO model disrupted lysosomal acidification, blocked intracellular vacuole formation, and impaired blastoid cavitation. Furthermore, genetic and pharmacological disruption of V-ATPase function significantly impaired cavitation in mouse and human blastocysts. Thus, our simple DMSO model effectively recapitulates human blastocyst cavitation and reveals an essential, conserved mechanism involving V-ATPase-mediated lysosomal acidification during early embryogenesis

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Early Embryonic Cell

SUBMITTER: Huoming Zhang  

LAB HEAD: Huoming Zhang

PROVIDER: PXD069054 | Pride | 2026-03-12

REPOSITORIES: Pride