Cambridge

Genome editing reveals a role for OCT4 in human embryogenesis

From Genome editing reveals a role for OCT4 in human embryogenesis : Nature

Despite their fundamental biological and clinical importance, the molecular mechanisms that regulate the first cell fate decisions in the human embryo are not well understood. Here we use CRISPR–Cas9-mediated genome editing to investigate the function of the pluripotency transcription factor OCT4 during human embryogenesis. We identified an efficient OCT4-targeting guide RNA using an inducible human embryonic stem cell-based system and microinjection of mouse zygotes. Using these refined methods, we efficiently and specifically targeted the gene encoding OCT4 (POU5F1) in diploid human zygotes and found that blastocyst development was compromised. Transcriptomics analysis revealed that, in POU5F1-null cells, gene expression was downregulated not only for extra-embryonic trophectoderm genes, such as CDX2, but also for regulators of the pluripotent epiblast, including NANOG. By contrast, Pou5f1-null mouse embryos maintained the expression of orthologous genes, and blastocyst development was established, but maintenance was compromised. We conclude that CRISPR–Cas9-mediated genome editing is a powerful method for investigating gene function in the context of human development.

CRISPR has revealed a clue in how human embryos begin to develop

From CRISPR breakthrough could drop miscarriage rates | TechCrunch

CRISPR Cas9 can modify or snip out genetic defects thought to contribute to miscarriage, but until now it wasn’t clear why some embryos continued to form into a fetus and others did not.

British scientists conducting the study found that a certain human genetic marker called OTC4 played an important role in the formation and development in the early stages of embryonic development. The scientists used CRISPR Cas9 to knock out this important gene in days-old human embryos and found that without it, these embryos ceased to attach or grow properly.

The findings could not only help us better understand why some women suffer more miscarriages than others, but it could also potentially greatly increase the rate of successful in vitro fertilization (IVF) procedures.