NatureJun 25, 2026

Gene editing shows NANOG is essential for early human embryo development

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 26, 2026

Abstract

Adenine base editing was applied to human embryos, resulting in a functional knockout of NANOG without triggering genotoxicity.

The study successfully targeted an exon splice donor site in human embryos using adenine base editing.
Loss of NANOG led to disrupted pluripotent epiblast specification, with cells differentiating towards primitive endoderm or trophectoderm programs.
NANOG knockout demonstrated a functional compensation mechanism in human embryos that differs from findings in mouse models.
The findings underscore the significance of NANOG in maintaining human pluripotency and epiblast specification.
This approach represents a novel method for functional studies of developmental regulators in human embryos.

Simplified

Understanding how the first cell lineages in human development are specified and maintained has fundamental importance and clinical implications for regenerative medicine, infertility and pregnancy loss. While mouse models have provided valuable insights into transcription factors regulating early development, translating these findings to human embryos has been limited by ethical, technical and biological constraints. Functional studies of transcription factors in human embryos have been hindered by nuclease-based genome-editing approaches that induce genotoxicity^1-3. To overcome this, we applied adenine base editing (ABE8e)^4,5 to precisely target an exon splice donor site, resulting in a splicing defect and functional knockout of NANOG, representing the first application of base editing to study a developmental regulator in human embryos. This approach did not trigger genotoxicity and showed limited off-target editing. Loss of NANOG disrupts pluripotent epiblast specification and instead cells differentiate toward a primitive endoderm (yolk sac) or trophectoderm (placental) transcriptional programme. Retention of primitive endoderm differentiation in NANOG-edited human embryos reveals a functional compensation distinct from mouse, underscoring the importance of directly investigating human development. Our findings demonstrate an essential role for NANOG in human pluripotency and epiblast specification, and highlight the utility of base editing for functional interrogation of human development.