Patterson Benjamin, Tanaka Yoshiaki, Park In-Hyun
Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA.
Tissue Eng Regen Med. 2017 Dec;14(6):643-652. doi: 10.1007/s13770-017-0096-4. Epub 2017 Nov 22.
Recent advances in stem cell biology have dramatically increased the understanding of molecular and cellular mechanism of pluripotency and cell fate determination. Additionally, pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), arose as essential resources for disease modeling and cellular therapeutics. Despite these advancements, the epigenetic dysregulation in pluripotency such as the imprinting status, and X chromosome dosage compensation, and its consequences on future utility of PSCs yet remain unresolved. In this review, we will focus on the X chromosome regulation in human PSCs (hPSCs). We will introduce the previous findings in the dosage compensation process on mouse model, and make comparison with those of human systems. Particularly, the biallelic X chromosome activation status of human preimplantation embryos, and the regulation of the active X chromosome by human specific lincRNA, XACT, will be discussed. We will also discuss the recent findings on higher order X chromosome architecture utilizing Hi-C, and abnormal X chromosome status in hPSCs.
干细胞生物学的最新进展极大地增进了我们对多能性和细胞命运决定的分子及细胞机制的理解。此外，多能干细胞（PSC），包括胚胎干细胞（ESC）和诱导多能干细胞（iPSC），已成为疾病建模和细胞治疗的重要资源。尽管取得了这些进展，但多能性中的表观遗传失调，如印记状态和X染色体剂量补偿，及其对PSC未来应用的影响仍未得到解决。在这篇综述中，我们将聚焦于人类多能干细胞（hPSC）中的X染色体调控。我们将介绍之前在小鼠模型剂量补偿过程中的研究发现，并与人类系统的研究发现进行比较。特别地，将讨论人类植入前胚胎的双等位基因X染色体激活状态，以及人类特异性长链非编码RNA XACT对活性X染色体的调控。我们还将讨论利用Hi-C技术在高阶X染色体结构方面的最新研究发现，以及hPSC中异常的X染色体状态。
