广州医科大学范勇等研究人员合作利用人类类囊胚，模拟早期原肠运动并呈现自然囊胚的DNA甲基化模式。2025年1月14日，《细胞—干细胞》杂志在线发表了这项成果。

使用4种化学物质和白血病抑制因子（LIF）（4CL）处理的初始人类多能干细胞（hPSC），研究人员开发了一种高保真度的类囊胚（4CL类囊胚）。4CL类囊胚在形态学和转录谱上与人类囊胚高度相似，展现出相似的DNA甲基化和基因印记模式。

通过将三维培养延长至14天，这些类囊胚模拟了早期的胚层形成，表现出细胞的特化和迁移。它们还显示了卡内基阶段6（CS6）时血管生成性血管母细胞（HAB）的转录特征。该模型弥合了植入前后阶段，为早期组织形成和人类发育提供了宝贵的见解。

据介绍，类囊胚是研究早期人类胚胎发生的有前途的模型，但现有模型在植入后发育上存在局限，且缺乏全面的表观遗传评估，特别是在基因组印记方面。这些问题可能导致在精确模拟早期胚胎发育时出现失败。

附：英文原文

Title: Modeling early gastrulation in human blastoids with DNA methylation patterns of natural blastocysts

Author: Han Xie, Chenrui An, Bing Bai, Jiajia Luo, Nianqin Sun, Baiquan Ci, Long Jin, Peiting Mo, Yawen Lu, Ke Zhong, Yang Yu, Tao Tan, Rong Li, Yong Fan

Issue&Volume: 2025-01-14

Abstract: Blastoids are a promising model for studying early human embryogenesis, but current models have limitations in post-implantation development and lack comprehensive epigenetic assessments, especially regarding genomic imprinting. These issues can lead to failures in accurately modeling early embryonic development. In this study, we developed a high-fidelity blastoid model using 4 chemicals + leukemia inhibitory factor (LIF) (4CL) naive human pluripotent stem cells (hPSCs) (4CL blastoids). 4CL blastoids closely resemble human blastocysts in morphology and transcriptional profiles, exhibiting similar DNA methylation and gene imprinting patterns. By extending the 3D culture to 14 days, these blastoids mimic early gastrulation, demonstrating the specification and migration of cells. They also show the transcriptional signature of hemogenic angioblast (HAB) cells at Carnegie stage 6 (CS6). This model bridges pre- and post-implantation stages, offering valuable insights into early tissue formation and human development.

DOI: 10.1016/j.stem.2024.12.010

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00450-8