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In the present study, we generated Tibetan-enriched M9a cytoplasmic hybrids (cybrids) and lowland-associated M7/8 cybrids using the trans-mitochondrial cybrid method in mtDNA-depleted 143B (TK) osteosarcoma cells, and then generated a stable EPAS1 knockdown cell line in M9a cybrids using lentiviral transduction to recapitulate the nuclear and mitochondrial adaptive genotype of the Tibetan population