美国加州大学圣地亚哥分校Prashant Mali和Kun Zhang团队合作在研究中取得进展。他们的最新研究将畸胎瘤作为人多谱系发育的模型。相关论文于2023年11月4日在线发表在《细胞》杂志上。
畸胎瘤是验证干细胞多能性的公认标准，研究人员提出畸胎瘤可作为研究人类发育过程的有效平台。对来源于4个细胞系的23个畸胎瘤的179,632个细胞进行单细胞RNA测序（RNA-seq），研究人员发现畸胎瘤在所有3个胚层中均包含约20种细胞类型，畸胎瘤间细胞类型的异质性可与类器官系统相媲美，畸胎瘤肠和脑细胞类型与胎儿相似的细胞类型非常吻合。
此外，细胞条形码还证实移植的干细胞能快速植入并有助于所有谱系的发育。使用CRISPR-Cas9敲除筛选，研究人员证明了畸胎瘤可以同时分析所有细胞层遗传扰动的影响。
同时，研究人员发现畸胎瘤可以通过microRNA（miRNA）调控的自杀基因表达来进行分子调控从而丰富特定组织。
综上所述，畸胎瘤可能是一个可用于多谱系发育建模、全组织功能基因筛选和组织工程的潜在平台。
附：英文原文
Title: Defining the Teratoma as a Model for Multi-lineage Human Development
Author: Daniella McDonald, Yan Wu, Amir Dailamy, Justin Tat, Udit Parekh, Dongxin Zhao, Michael Hu, Ann Tipps, Kun Zhang, Prashant Mali
Issue&Volume: 2023-11-04
Abstract: We propose that the teratoma, a recognized standard for validating pluripotency instem cells, could be a promising platform for studying human developmental processes.Performing single-cell RNA sequencing (RNA-seq) of 179,632 cells across 23 teratomasfrom 4 cell lines, we found that teratomas reproducibly contain approximately 20 celltypes across all 3 germ layers, that inter-teratoma cell type heterogeneity is comparablewith organoid systems, and teratoma gut and brain cell types correspond well to similarfetal cell types. Furthermore, cellular barcoding confirmed that injected stem cellsrobustly engraft and contribute to all lineages. Using pooled CRISPR-Cas9 knockoutscreens, we showed that teratomas can enable simultaneous assaying of the effectsof genetic perturbations across all germ layers. Additionally, we demonstrated thatteratomas can be sculpted molecularly via microRNA (miRNA)-regulated suicide geneexpression to enrich for specific tissues. Taken together, teratomas are a promisingplatform for modeling multi-lineage development, pan-tissue functional genetic screening,and tissue engineering.
DOI: 10.1016/j.cell.2023.10.018
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31381-7
期刊信息 Cell：《细胞》，创刊于1974年。隶属于细胞出版社，最新IF：36.216官方网址：https://www.cell.com/投稿