Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Cell Prolif. 2023 Sep;56(9):e13436. doi: 10.1111/cpr.13436. Epub 2023 Mar 1.
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.
单倍体胚胎干细胞 (haESCs) 来源于单倍体囊胚的内细胞团，只含有一组染色体。在 haESC 衍生过程中会发生广泛而精确的染色质重塑，但 haESC 的固有转录组特征和染色质结构尚未得到充分探索。我们对四个小鼠 haESC 系的转录组、核小体定位和关键组蛋白修饰进行了分析，并将这些图谱与其他密切相关的干细胞系、MII 卵母细胞、圆形精子细胞、精子和小鼠胚胎成纤维细胞进行了比较。haESCs 的转录组图谱更接近原始多能干细胞。与 haESCs 中的一条 X 染色体一致，Xist 被抑制，表明没有 X 染色体失活。haESCs 和 ESCs 具有相似的全局染色质结构。然而，在 ESCs 中鉴定出 2056 个启动子中有核小体缺失区，而在 haESCs 中不存在。此外，在 haESCs 和 ESCs 中，转录因子基序和核小体之间形成了三种特征性的空间关系，特别是在连接区、核小体中央表面和核小体边界。此外，在 haESCs 中 4259 个增强子的染色质状态关闭，但在 ESCs 中是活跃的。对这些增强子的功能注释表明，它们在细胞周期调控中富集，这是 haESC 自我二倍化的主要报道机制。值得注意的是，haESCs 的转录组图谱和染色质结构在传代过程中高度保存，但与分化细胞类型不同。
