中南大学Ge Lin和中国科学院大学Zhouchun Shang研究组合作报道，人整倍体和非整倍体囊胚的单细胞转录组图谱。相关论文于2024年6月5日发表在《自然-遗传学》杂志上。

据介绍，人类早期胚胎中经常检测到非整倍体，这是导致早期妊娠失败的主要原因之一。然而，尚不清楚非整倍体是如何影响细胞功能。

研究人员分析了203个具有常染色体和性染色体人整倍体和非整倍体囊胚中14908个单细胞转录组。几乎所有囊胚都包含四种普系。在非整倍体染色体中，19.5%±1.2%的表达基因表现出剂量效应，并发现了90个剂量敏感区域。非整倍体导致普遍的全基因组转录组改变。

研究发现了包括细胞凋亡在内的共同效应，尤其是在单倍体中，这部分解释了常染色体单倍体细胞数量较少的原因。研究进一步确定了在非整倍体中造成上胚层发育不稳定的系特异性效应，这种效应伴随着TGF-β和FGF信号的下调，并导致滋养层成熟不足。该研究为理解人类非整倍体囊胚的分子基础提供了重要见解，并可能揭示囊胚发育过程中细胞间的相互作用。

附：英文原文

Title: A single-cell transcriptome atlas of human euploid and aneuploid blastocysts

Author: Wang, Shengpeng, Leng, Lizhi, Wang, Quanlei, Gu, Yifan, Li, Jinlu, An, Yanru, Deng, Qiuting, Xie, Pingyuan, Cheng, Can, Chen, Xueqin, Zhou, Qinwei, Lu, Jia, Chen, Fang, Liu, Longqi, Yang, Huanming, Wang, Jian, Xu, Xun, Hou, Yong, Gong, Fei, Hu, Liang, Lu, Guangxiu, Shang, Zhouchun, Lin, Ge

Issue&Volume: 2024-06-05

Abstract: Aneuploidy is frequently detected in early human embryos as a major cause of early pregnancy failure. However, how aneuploidy affects cellular function remains elusive. Here, we profiled the transcriptomes of 14,908 single cells from 203 human euploid and aneuploid blastocysts involving autosomal and sex chromosomes. Nearly all of the blastocysts contained four lineages. In aneuploid chromosomes, 19.5%±1.2% of the expressed genes showed a dosage effect, and 90 dosage-sensitive domains were identified. Aneuploidy leads to prevalent genome-wide transcriptome alterations. Common effects, including apoptosis, were identified, especially in monosomies, partially explaining the lower cell numbers in autosomal monosomies. We further identified lineage-specific effects causing unstable epiblast development in aneuploidies, which was accompanied by the downregulation of TGF-β and FGF signaling, which resulted in insufficient trophectoderm maturation. Our work provides crucial insights into the molecular basis of human aneuploid blastocysts and may shed light on the cellular interaction during blastocyst development.

DOI: 10.1038/s41588-024-01788-6

Source: https://www.nature.com/articles/s41588-024-01788-6