Routes to Reprogramming

Pluripotent stem cells, which give rise to almost all cell types, can be engineered from mature cells. A thorough analysis of the process has led to the characterization of a new type of pluripotent cell. See Articles p.192 & p.198

Scientists have been reprogramming adult cells into embryonic ones for decades — but they are only now getting to grips with the mechanics.

Five papers report extensive transcriptomic, epigenomic and proteomic analyses of reprogramming, revealing the existence of several reprogramming routes and multiple unique pluripotent cell states.

This study presents an extensive molecular characterization of the reprograming process by analysis of transcriptomic, epigenomic and proteomic data sets describing the routes to pluripotency; it finds distinct routes towards two stable pluripotent states characterized by distinct epigenetic events.

The forced expression of key transcription factors can induce somatic cells to acquire pluripotency characteristics; here high levels of reprogramming factors are used to induce mouse embryonic fibroblasts to a stable alternative pluripotent state with low intercellular adhesion.

Somatic cell reprogramming can induce distinct pluripotent states. Here the authors perform time-resolved small RNA expression profiling during the reprogramming of mouse embryonic fibroblasts and observe that distinct miRNA milieus characterise alternate states of pluripotency.

During somatic cell reprogramming, the cell transits through intermediate states. Here, the authors perform an in-depth quantitative proteomic analysis of the reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells and observe two waves of proteome reorganisation.

Somatic cell reprogramming can induce distinct pluripotent states. Here the authors perform time-resolved whole-genome bisulfite sequencing during the reprogramming of mouse embryonic fibroblasts and report dynamic global DNA methylation changes.