Distinct roles of Bdh2 in regulating embryonic stem cell fate

To further gain insights into the role of Bdh2 in cell fate decisions of mouse ESCs, we generated Bdh2 homozygous knockout mouse advanced pluripotent embryonic stem cell (ASC) and embryonic stem cell (ESC) lines by CRISPR/Cas9 genome editing technology. Bdh2 deficiency in ASCs/ESCs exhibited no effect on expression of core pluripotent transcription factors and alkaline phosphatase activity, suggesting dispensability of Bdh2 for self-renewal and pluripotency of embryonic stem cells. Notebly, Bdh2-knockout ASCs/ESCs exhibit higher expression of the endodermal somatic genes, Gata4, Gata6, Sox17,and also colocalizated with Oct4. Importantly, expression of key DNA methylation genes Dnmt3a, Dnmt3b and Dnmt1 decreased in Bdh2-knockout ASCs/ESCs. Overall, we provide insight on understanding of earliest cell fate decicion in ASCs/ESCs and a new avenue to create and preserve pioneer lineage precursors with pluripotency. Overall design: 3 replicates of mRNA of mouse embryonic stem cells mRNA profiles of wild type (WT) and Bdh2-/- cell lines