Chromatin landscape dynamics during reprogramming towards human naïve and primed pluripotency reveals the divergent function of PRDM1 isoforms

Cell Death Discovery, 2024 · DOI: https://doi.org/10.1038/s41420-024-02230-w · Published: October 25, 2024

Simple Explanation

The study investigates the chromatin landscape dynamics during reprogramming towards human naïve and primed pluripotency. It focuses on identifying key transcriptional and epigenetic factors involved in reprogramming-associated chromatin remodeling. The research highlights the different roles of PRDM1α and PRDM1β isoforms in the naïve reprogramming process.

Study Duration

Not specified

Participants

hiF-T cells, iPSCs

Evidence Level

Not specified

Key Findings

1
PRDM1α and PRDM1β bind to distinct genomic loci and play different roles in the naïve reprogramming process.
2
Neither PRDM1α nor PRDM1β is indispensable to maintaining naïve pluripotency.
3
PRDM1α and PRDM1β targeted different genomic loci.

Research Summary

This study maps chromatin accessibility during human somatic reprogramming to naïve and primed pluripotency, delineating distinct cell fate trajectories. PRDM1 is identified as a crucial transcription factor in chromatin remodeling during reprogramming, with its knockdown resulting in fewer but morphologically enhanced colonies during naïve reprogramming. Two isoforms of PRDM1, PRDM1α and PRDM1β, have divergent influences on reprogramming to naïve pluripotency; neither is essential for maintaining naïve pluripotency.

Practical Implications

Improved Reprogramming Efficiency

Precise regulation of key transcription factors can help improve reprogramming efficiency and obtain higher quality iPSCs.

Clinical Application Foundation

The findings lay the foundation for clinical applications by providing insights into directing the fates of pluripotent cells.

Understanding PRDM1 Function

The study enriches the understanding of the PRDM protein family’s function, particularly the yin-yang paradigm of its isoforms.

Study Limitations

1
The study lacks capturing endogenous proteins for delineating the binding profiles of PRDM1α and PRDM1β.
2
There are only a few time points studied due to sample size and cost constraints.
3
The auto-regulation model requires further experimental validation, such as biochemical evidence demonstrating the antagonistic effect of PRDM1β on PRDM1α.

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