Deficiency Promotes Endoderm-Biased Early Differentiation of Mouse Embryonic Stem Cells.

3-hydroxybutyrate dehydrogenase-2 (), a short-chain dehydrogenase, catalyzes a rate-limiting step in the biogenesis of the mammalian siderophore, playing a key role in iron homeostasis, energy metabolism and apoptosis. However, the function of in embryonic stem cells (ESCs) remains unknown. To gain insights into the role of on pluripotency and cell fate decisions of mouse ESCs, we generated homozygous knockout lines for both mouse advanced embryonic stem cell (ASC) and ESC using CRISPR/Cas9 genome editing technology. deficiency in both ASCs and ESCs had no effect on expression of core pluripotent transcription factors and alkaline phosphatase activity, suggesting dispensability of for self-renewal and pluripotency of ESCs. Interestingly, cells with deficiency exhibited potency of endoderm differentiation ; with upregulated endoderm associated genes revealed by RNA-seq and RT-qPCR. We further demonstrate that loss inhibited expression of multiple methyltransferases (DNMTs) at both RNA and protein level, suggesting that may be essentially required to maintain DNA methylation in ASCs and ESCs. Overall, this study provides valuable data and resources for understanding how regulate earliest cell fate decision and DNA methylation in ASCs/ESCs.