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Although Hcy accumulation can occur clinically as a result of B 12 insufficiency in humans 26 , we observed that induced pluripotent stem (iPS) cells upregulate the expression of genes encoding two main consumers of Hcy: cystathionine beta-synthase (CBS, which initiates the transsulfuration pathway) and betaine-homocysteine methyltransferase (BHMT, which synthesizes Met using Hcy and betaine in an MS-independent manner