美国华盛顿大学医学院Thorold W. Theunissen等研究人员合作发现，干细胞来源的滋养层细胞器官可模拟人类胎盘发育和对新出现病原体的易感性。2022年5月5日出版的《细胞—干细胞》杂志发表了这项成果。

研究人员发现，从初始的人类多能干细胞（hPSC）中分离出来的滋养细胞可以有效地自我组织成三维干细胞衍生的滋养细胞器官（SC-TO），其绒毛结构类似于原始滋养细胞器官。单细胞转录组分析显示，存在不同的细胞滋养细胞和合胞滋养细胞集群以及一小簇绒毛外滋养细胞，这与植入后胚胎中的滋养细胞身份密切相关。这些类器官培养物显示出先前在人类胎盘中描述的克隆性X染色体失活模式。

研究人员进一步证明，SC-TO对新出现的病原体（SARS-CoV-2和寨卡病毒）表现出选择性的脆弱性，这与它们各自进入因子的表达水平相关。从初始的hPSC生成滋养细胞器官，为发育中的胎盘及其对新出现病原体的敏感性提供了一个可利用的三维模型系统。

据介绍，来自胎盘绒毛的滋养细胞器官提供了一个人类胎盘发育的三维模型系统，但获得早孕期组织的机会有限。

附：英文原文

Title: Stem-cell-derived trophoblast organoids model human placental development and susceptibility to emerging pathogens

Author: Rowan M. Karvas, Shafqat A. Khan, Sonam Verma, Yan Yin, Devesha Kulkarni, Chen Dong, Kyoung-mi Park, Brian Chew, Eshan Sane, Laura A. Fischer, Deepak Kumar, Liang Ma, Adrianus C.M. Boon, Sabine Dietmann, Indira U. Mysorekar, Thorold W. Theunissen

Issue&Volume: 2022/05/05

Abstract: Trophoblast organoids derived from placental villi provide a 3D model system of humanplacental development, but access to first-trimester tissues is limited. Here, wereport that trophoblast stem cells isolated from naive human pluripotent stem cells(hPSCs) can efficiently self-organize into 3D stem-cell-derived trophoblast organoids(SC-TOs) with a villous architecture similar to primary trophoblast organoids. Single-celltranscriptome analysis reveals the presence of distinct cytotrophoblast and syncytiotrophoblastclusters and a small cluster of extravillous trophoblasts, which closely correspondto trophoblast identities in the post-implantation embryo. These organoid culturesdisplay clonal X chromosome inactivation patterns previously described in the humanplacenta. We further demonstrate that SC-TOs exhibit selective vulnerability to emergingpathogens (SARS-CoV-2 and Zika virus), which correlates with expression levels oftheir respective entry factors. The generation of trophoblast organoids from naivehPSCs provides an accessible 3D model system of the developing placenta and its susceptibilityto emerging pathogens.

DOI: 10.1016/j.stem.2022.04.004

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00157-6