Reprogramming articles from across Nature Portfolio

Epigenetic reprogramming involves global loss of DNA methylation, but how this is regulated is not completely understood. Here, Tan et al. run a reverse genetic screen and report that nuclear DNMT1 is finetuned by maternal factor Pramel15 through proteasomal degradation in mouse zygotes.

Histone crotonylation has been shown to regulate transcription in multiple settings, but its role during preimplantation development has not been examined. Here they show that P300 regulated crotonylation during embryonic development and that H3K18cr marks active promoters in embryos, crucial for transcriptional activation and embryonic fate determination.

Cell fate decisions remain poorly understood at the molecular level. Here Ming et al. show that BMP4 as the signal diverting cell fate away from epiblast/pluripotency to hypoblast/primitive endoderm fate during JGES reprogramming by promoting the dissociation of SALL4 from NuRD.

Human pancreatic δ cells play important roles in the balance of pancreatic hormones. Here, the authors develop a directed differentiation method to generate in vitro and in vivo functional δ cells from human stem cells by combining FGF2 with FGF7.

Cell fate is principally regulated by a common machine or cell-intrinsic machine. Here the authors report the design and testing of an engineered chromatin controller to drive such machine for mouse cell fate transition in precision.

Dystrophic Epidermolysis Bullosa is an uncurable monogenetic skin disease. Here, Neumayer et al. develop a cGMP-compatible CRISPR- and iPS cell-based approach that produces gene-corrected, autologous skin composite grafts for definitive treatment.

Xu and colleagues used partial OSKM reprogramming in aged mice to drive cell-type proportions of the subventricular zone to more youthful levels, which equates to qualified rejuvenation of a neurogenic niche that is defined, in part, by restoration of neuroblast levels.

In vivo reprogramming by expression of the transcription factors OCT4, SOX2, KLF4, and MYC (OSKM factors) has been associated with early mortality and cancer. We report that these adverse effects are associated with liver and intestinal dysfunction. Strategic control of OSKM expression in these organs through a newly developed transgenic mouse model reduced adverse effects. Our model yields valuable insights into the potential of in vivo reprogramming for rejuvenation and regeneration.

By analysing the effect of disrupting microbiota during in vivo reprogramming, Kovatcheva et al. demonstrated that vitamin B₁₂-dependent metabolism is a limiting factor for cellular reprogramming and plasticity, and propose its therapeutic supplementation for the improvement of tissue repair.