State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
Shunde Hospital of Southern Medical University, Shunde, Guangdong, China.
Int J Biol Sci. 2021 Jan 1;17(2):527-538. doi: 10.7150/ijbs.55873. eCollection 2021.
Germline specification is a fundamental step for human reproduction and this biological phenomenon possesses technical challenges to study as it occurs immediately after blastocyst implantation. The establishment of human primordial germ cell-like cells (hPGCLCs) induction system allows sophisticated characterization of human primordial germ cells (hPGCs) development. However, the underlying molecular mechanisms of hPGCLC specification are not fully elucidated. Here, we observed particularly high expression of the histone demethylase in male fetal germ cells (FGCs) but not in male somatic cells. Besides, shared similar expression pattern with hPGC marker genes in hPGCLCs, suggesting an important role of in germ cell development. Although deletion of had no significant effects on human embryonic stem cell (hESC)'s pluripotency, loss of dramatically impaired hPGCLCs differentiation whereas ectopically expressed KDM2B could efficiently rescue such defect, indicating this defect was due to 's loss in hPGCLC specification. Mechanistically, as revealed by the transcriptional profiling, suppressed the expression of somatic genes thus inhibited somatic differentiation during hPGCLC specification. These data collectively indicate that KDM2B is an indispensable epigenetic regulator for hPGCLC specification, shedding lights on how epigenetic regulations orchestrate transcriptional events in hPGC development for future investigation.
生殖系细胞的特化是人类生殖的一个基本步骤，由于该生物学现象发生在囊胚植入后不久，因此对其进行研究具有技术挑战。人类原始生殖细胞样细胞（hPGCLCs）诱导系统的建立允许对人类原始生殖细胞（hPGCs）的发育进行复杂的表征。然而，hPGCLC 特化的潜在分子机制尚未完全阐明。在这里，我们观察到组蛋白去甲基酶 在雄性胎儿生殖细胞（FGCs）中的表达特别高，但在雄性体细胞中却没有表达。此外， 在 hPGCLCs 中与 hPGC 标记基因具有相似的表达模式，这表明 在生殖细胞发育中具有重要作用。虽然 删除对人胚胎干细胞（hESC）的多能性没有显著影响，但 的缺失严重损害了 hPGCLCs 的分化，而过表达 KDM2B 可以有效地挽救这种缺陷，这表明这种缺陷是由于 hPGCLC 特化过程中 的缺失所致。从转录谱来看， 抑制了体细胞基因的表达，从而在 hPGCLC 特化过程中抑制了体细胞分化。这些数据共同表明，KDM2B 是 hPGCLC 特化所必需的表观遗传调节剂，为未来研究如何通过表观遗传调控协调 hPGC 发育中的转录事件提供了线索。
