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

IF 19.8 1区医学 Q1 CELL & TISSUE ENGINEERING

Cell stem cell Pub Date : 2025-01-14 DOI:10.1016/j.stem.2024.12.010

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

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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.

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利用天然囊胚的 DNA 甲基化模式模拟人类囊胚的早期胚胎发育

囊胚是研究早期人类胚胎发生的一个很有前途的模型，但目前的模型在着床后发育方面存在局限性，缺乏全面的表观遗传学评估，特别是基因组印迹。这些问题可能导致无法准确地模拟早期胚胎发育。在这项研究中，我们用4种化学物质+白血病抑制因子（LIF）（4CL）幼稚人多能干细胞（hPSCs）（4CL囊胚）建立了一个高保真的囊胚模型。4CL囊胚在形态和转录谱上与人类囊胚非常相似，表现出相似的DNA甲基化和基因印迹模式。通过将3D培养延长到14天，这些囊胚模拟了早期原肠胚形成，展示了细胞的规格和迁移。它们还显示了卡内基6期（CS6）造血成血管细胞（HAB）细胞的转录特征。该模型连接了植入前和植入后阶段，为早期组织形成和人类发育提供了有价值的见解。

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来源期刊

Cell stem cell 生物-细胞生物学

CiteScore

37.10

自引率

2.50%

发文量

151

审稿时长

42 days

期刊介绍： Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.