p16High senescence restricts cellular plasticity during somatic cell reprogramming

Using genetic and chemical approaches to manipulate senescent cells, we found that removal of p16High cells resulted in four factor (4F)-induced reprogramming (4FR) of somatic cells into totipotent-like stem cells. These cells expressed markers of both pluripotency and the 2-cell (2C) embryonic state, readily formed implantation-competent blastocyst-like structures, blastoids, and following morula aggregation, contributed to embryonic and extraembryonic lineages in E12.5 embryos.