Transcriptome profiles and chromatin states in mouse androgenetic haploid embryonic stem cells

Abstract

Haploid embryonic stem cells (haESCs) are derived from the inner cell mass of the haploid blastocyst, containing only one set of chromosomes. Extensive and accurate chromatin remodelling occurs during haESC derivation, but the intrinsic transcriptome profiles and chromatin structure of haESCs have not been fully explored. We profiled the transcriptomes, nucleosome positioning, and key histone modifications of four mouse haESC lines, and compared these profiles with those of other closely‐related stem cell lines, MII oocytes, round spermatids, sperm, and mouse embryonic fibroblasts. haESCs had transcriptome profiles closer to those of naïve pluripotent stem cells. Consistent with the one X chromosome in haESCs, Xist was repressed, indicating no X chromosome inactivation. haESCs and ESCs shared a similar global chromatin structure. However, a nucleosome depletion region was identified in 2056 promoters in ESCs, which was absent in haESCs. Furthermore, three characteristic spatial relationships were formed between transcription factor motifs and nucleosomes in both haESCs and ESCs, specifically in the linker region, on the nucleosome central surface, and nucleosome borders. Furthermore, the chromatin state of 4259 enhancers was off in haESCs but active in ESCs. Functional annotation of these enhancers revealed enrichment in regulation of the cell cycle, a predominantly reported mechanism of haESC self‐diploidization. Notably, the transcriptome profiles and chromatin structure of haESCs were highly preserved during passaging but different from those of differentiated cell types.

Quantitative Biofabrication Platform for Collagen‐Based Peripheral Nerve Grafts with Structural and Chemical Guidance

“…In addition, the viscosity of collagen restricts its release over time, leading to a phenomenon known as transport relaxation. [ 18 ] This effect poses significant challenges to achieving accurate control of the extrusion volume. To overcome this issue, we developed a model‐based approach to control the concentration gradients (Figure 3C).…”

“…Soluble core materials, distinct from traditional sacrificial materials, are specifically engineered to dissolve and create intricate microchannels within bioprinted constructs such as peripheral nerves and vascularized tissues. [ 18 ] Therefore, ideal soluble core materials have more requirements than sacrificial materials. First, they should possess a higher yield strength than the bulk material to avoid distortion caused by the compression of the bulk filaments.…”

“…In this study, we adopted a distinct modeling perspective. Specifically, we revealed that the relaxation phenomenon occurs during the transport process of viscoelastic inks [ 18 ] and proposed a comprehensive dynamic model. Using this mechanical model, we derived and simplified the core equations, resulting in the single‐parameter model presented in this study.…”

“…Consequently, it ensures the consistent quality of individual grafts, with reproducibility and consistency being fundamental for future endeavors aimed at commercialization. Moreover, our platform accommodates personalized design and fabrication [ 18 ] specifically tailored to a diverse range of neural injury cases and effectively addressing the unique needs of patients. This approach has immense potential to deliver differentiated value‐added products and services, thereby empowering medical institutions to meet a broader spectrum of demands.…”

“…In addition, achieving real-time control over the precise neurotrophic factor ratio poses a significant challenge, given the lack of a precise microextrusion control method for viscoelastic inks. Consequently, the integration of chemical cues into collagen-based nerve-like structures using a one-step bioprinting approach [14][15][16][17][18] remains a challenge. [19] In this study, we develop an integrated quantitative biofabrication platform for the fabrication of collagen nerve grafts.…”