瑞典卡罗琳斯卡学院Fredrik Lanner等研究人员合作开发出使用单细胞RNA测序数据的全面人类胚胎参考工具。相关论文于2024年11月14日在线发表在《自然—方法学》杂志上。

研究人员表示，基于干细胞的胚胎模型为研究早期人类发育提供了前所未有的实验工具。胚胎模型的有用性依赖于其分子、细胞和结构上与体内胚胎的相似性。为了验证人类胚胎模型，单细胞RNA测序已被用于无偏的转录组分析。然而，作为通用参考以评估人类胚胎模型的组织化和集成化人类单细胞RNA测序数据集仍然缺乏。

研究人员通过整合六个已发布的人类数据集，开发了这样的参考工具，这些数据集涵盖了从受精卵到胚盘期的发育。通过与现有的人类和非人类灵长类数据集对比和验证谱系注释，并使用稳定的统一流形近似与投影（UMAP），研究人员构建了一个早期胚胎发生预测工具，查询数据集可以在参考工具中进行投影，并注释预测的细胞身份。利用此参考工具，研究人员检查了已发布的人类胚胎模型，强调了在没有相关参考进行基准化和验证时，可能出现的误注释风险。

附：英文原文

Title: A comprehensive human embryo reference tool using single-cell RNA-sequencing data

Author: Zhao, Cheng, Plaza Reyes, Alvaro, Schell, John Paul, Weltner, Jere, Ortega, Nicols M., Zheng, Yi, Bjrklund, sa K., Baqu-Vidal, Laura, Sokka, Joonas, Torokovic, Ras, Cox, Brian, Rossant, Janet, Fu, Jianping, Petropoulos, Sophie, Lanner, Fredrik

Issue&Volume: 2024-11-14

Abstract: Stem cell-based embryo models offer unprecedented experimental tools for studying early human development. The usefulness of embryo models hinges on their molecular, cellular and structural fidelities to their in vivo counterparts. To authenticate human embryo models, single-cell RNA sequencing has been utilized for unbiased transcriptional profiling. However, an organized and integrated human single-cell RNA-sequencing dataset, serving as a universal reference for benchmarking human embryo models, remains unavailable. Here we developed such a reference through the integration of six published human datasets covering development from the zygote to the gastrula. Lineage annotations are contrasted and validated with available human and nonhuman primate datasets. Using stabilized Uniform Manifold Approximation and Projection, we constructed an early embryogenesis prediction tool, where query datasets can be projected on the reference and annotated with predicted cell identities. Using this reference tool, we examined published human embryo models, highlighting the risk of misannotation when relevant references are not utilized for benchmarking and authentication.

DOI: 10.1038/s41592-024-02493-2

Source: https://www.nature.com/articles/s41592-024-02493-2