Cell Prolif., 2023 · DOI: 10.1111/cpr.13436 · Published: September 1, 2023
Haploid embryonic stem cells (haESCs) are unique stem cells with only one set of chromosomes, derived from the inner cell mass of haploid blastocysts. These cells undergo chromatin remodeling during derivation, influencing their transcriptome profiles and chromatin structure. This study investigates the transcriptome, nucleosome positioning, and histone modifications of mouse haESC lines, comparing them with other stem cells, oocytes, spermatids, sperm, and fibroblasts to understand their unique characteristics. The research reveals that haESCs have transcriptome profiles closer to naïve pluripotent stem cells, and unlike regular cells, Xist is repressed, meaning no X chromosome inactivation occurs. While haESCs and ESCs share a similar global chromatin structure, some differences exist, like a nucleosome depletion region present in ESCs but absent in haESCs. Furthermore, the study identifies characteristic spatial relationships between transcription factor motifs and nucleosomes in both haESCs and ESCs. Interestingly, specific enhancers are off in haESCs but active in ESCs, these are linked to cell cycle regulation, a mechanism related to haESC self-diploidization. Notably, the examined properties of haESCs remain consistent through passaging, but differ from differentiated cells.
The study provides insights into the unique transcriptome profile and chromatin structure of haESCs, highlighting their similarities to naïve pluripotent stem cells and differences from other cell types.
The identification of specific enhancers that are off in haESCs but active in ESCs, and their link to cell cycle regulation, offers potential epigenetic targets to reduce self-diploidization, facilitating haESC maintenance and applications.
The study contributes to the understanding of how haESCs can be used in genetic analysis and assisted reproduction, providing a basis for improving their stability and functionality in these contexts.