Klf5 establishes bi-potential cell fate by dual regulation of ICM and TE specification genes

• DOI: 10.1016/j.celrep.2021.109982
• Publication Date: 2021-11-09T17:54:07Z
• Authors: Martin Kinisu; Yong Jin Choi; Claudia Cattoglio; Ke Liu; Hector Roux de Be...; Raeline Valbuena; Nicole Pum; Sandrine Dudoit; Haiyan Huang; Zhenyu Xuan; Sang Yong Kim; Lin He
• Keywords: Cell fate determination; Inner cell mass; KLF4; Blastomere

Early blastomeres of mouse preimplantation embryos exhibit bi-potential cell fate, capable generating both embryonic and extra-embryonic lineages in blastocysts. Here we identify three major two-cell-stage (2C)-specific endogenous retroviruses (ERVs) as the molecular hallmark this plasticity. Using long terminal repeats (LTRs) all 2C-specific ERVs, Krüppel-like factor 5 (Klf5) their upstream regulator. Klf5 is essential for fate; a single Klf5-overexpressing stem (ESC) generates terminally differentiated chimeric embryos, directly induces inner mass (ICM) trophectoderm (TE) specification genes. Intriguingly, Klf4 act redundantly during ICM specification, whereas deficiency alone impairs TE specification. regulated by multiple transcription factors, particularly Dux, Dux/Klf5 axis evolutionarily conserved. The program converges on to establish enabling state with dual activation