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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-02807-z

摘要内容如下：

组织特异性胎儿干细胞的分离和主要类器官的衍生仅限于从终止妊娠获得的样本，妨碍了胎儿发育和先天性疾病的产前调查。因此，需要新的患者特异性体外模型。为此，在妊娠期间分离和扩增胎儿干细胞，而不需要组织样本或重新编程，将是有利的。羊水（AF）是多个发育器官的细胞来源。使用单细胞分析，我们描述了人类房颤中存在的细胞特性。我们鉴定并分离了胎儿胃肠道、肾脏和肺部来源的上皮干/祖细胞。培养后，这些细胞形成克隆上皮类器官，表现出小肠、肾小管和肺的特性。AF类器官表现出其组织来源的转录组、蛋白质表达和功能特征。与产前疾病模型相关，我们从先天性膈疝胎儿的AF和气管液细胞中获得肺类器官，概括了该疾病的一些特征。房颤类器官是在与产前干预相一致的时间线上衍生的，有可能允许对临床相关发育阶段的胎儿进行个性化的治疗工具和再生医学策略的研究。

英文原文如下：

Abstracts

Isolation of tissue-specific fetal stem cells and derivation of primary organoids is limited to samples obtained from termination of pregnancies, hampering prenatal investigation of fetal development and congenital diseases. Therefore, new patient-specific in vitro models are needed. To this aim, isolation and expansion of fetal stem cells during pregnancy, without the need for tissue samples or reprogramming, would be advantageous. Amniotic fluid (AF) is a source of cells from multiple developing organs. Using single-cell analysis, we characterized the cellular identities present in human AF. We identified and isolated viable epithelial stem/progenitor cells of fetal gastrointestinal, renal and pulmonary origin. Upon culture, these cells formed clonal epithelial organoids, manifesting small intestine, kidney tubule and lung identity. AF organoids exhibit transcriptomic, protein expression and functional features of their tissue of origin. With relevance for prenatal disease modeling, we derived lung organoids from AF and tracheal fluid cells of congenital diaphragmatic hernia fetuses, recapitulating some features of the disease. AF organoids are derived in a timeline compatible with prenatal intervention, potentially allowing investigation of therapeutic tools and regenerative medicine strategies personalized to the fetus at clinically relevant developmental stages.

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