Stem-cell-derived trophoblast organoids model human placental development and susceptibility to emerging pathogens.
Stem-cell-derived trophoblast organoids model human placental development and susceptibility to emerging pathogens.
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DOI：
10.1016/j.stem.2022.04.004
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发表时间：
2022-05-05
期刊：
影响因子：
23.9
通讯作者：
Theunissen, Thorold W.
中科院分区：
文献类型：
--
作者：
Karvas, Rowan M.;Khan, Shafqat A.;Verma, Sonam;Yin, Yan;Kulkarni, Devesha;Dong, Chen;Park, Kyoung-mi;Chew, Brian;Shane, Eshan;Fischer, Laura A.;Kumar, Deepak;Ma, Liang;Boon, Adrianus C. M.;Dietmann, Sabine;Mysorekar, Indira U.;Theunissen, Thorold W.
来源于胎盘绒毛的滋养层类器官提供了人类胎盘发育的3D模型系统，但获得早期妊娠组织的机会有限。在这里，我们报告说，从幼稚的人类多能干细胞（hPSC）分离的滋养层干细胞可以有效地自组织成3D干细胞衍生的滋养层类器官（SC-TO），其绒毛结构类似于初级滋养层类器官。单细胞转录组分析揭示了存在不同的细胞滋养层和合体滋养层集群和绒毛外滋养层的一个小集群，这密切对应于滋养层身份在植入后胚胎。这些类器官培养物显示了先前在人胎盘中描述的克隆X染色体失活模式。我们进一步证明，SC-TO表现出对新兴病原体（SARS-CoV-2和寨卡病毒）的选择性脆弱性，这与其各自的进入因子的表达水平相关。从幼稚hPSC产生滋养层类器官提供了发育中的胎盘及其对新兴病原体的易感性的可访问的3D模型系统。泰尼森等人描述了一种用于从幼稚的人多能干细胞衍生自我更新的3D滋养层类器官的方法。他们证明干细胞衍生的滋养层类器官模拟人类胎盘发育，X染色体失活和胎盘对新兴病毒病原体（SARS-CoV-2和寨卡病毒）感染的易感性。
Trophoblast organoids derived from placental villi provide a 3D model system of human placental development, but access to first-trimester tissues is limited. Here we report that trophoblast stem cells isolated from naïve 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 cell transcriptome analysis reveals the presence of distinct cytotrophoblast and syncytiotrophoblast clusters and a small cluster of extravillous trophoblasts, which closely correspond to trophoblast identities in the post-implantation embryo. These organoid cultures display clonal X chromosome inactivation patterns previously described in the human placenta. We further demonstrate that SC-TOs exhibit selective vulnerability to emerging pathogens (SARS-CoV-2 and Zika virus), which correlates with expression levels of their respective entry factors. The generation of trophoblast organoids from naïve hPSCs provides an accessible 3D model system of the developing placenta and its susceptibility to emerging pathogens. Theunissen et al. describe a methodology for deriving self-renewing 3D trophoblast organoids from naïve human pluripotent stem cells. They demonstrate that stem cell-derived trophoblast organoids model human placental development, X chromosome inactivation, and placental susceptibility to infection by emerging viral pathogens (SARS-CoV-2 and Zika virus).
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DOI：
10.1056/nejmoa1602412
发表时间：
2016-12-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brasil P;Pereira JP Jr;Moreira ME;Ribeiro Nogueira RM;Damasceno L;Wakimoto M;Rabello RS;Valderramos SG;Halai UA;Salles TS;Zin AA;Horovitz D;Daltro P;Boechat M;Raja Gabaglia C;Carvalho de Sequeira P;Pilotto JH;Medialdea-Carrera R;Cotrim da Cunha D;Abreu de Carvalho LM;Pone M;Machado Siqueira A;Calvet GA;Rodrigues Baião AE;Neves ES;Nassar de Carvalho PR;Hasue RH;Marschik PB;Einspieler C;Janzen C;Cherry JD;Bispo de Filippis AM;Nielsen-Saines K
通讯作者：
Nielsen-Saines K
影响因子：
30.3
作者：
Case, James Brett;Rothlauf, Paul W.;Whelan, Sean P. J.
通讯作者：
Whelan, Sean P. J.
影响因子：
7.7
作者：
Dong, Chen;Beltcheva, Mariana;Theunissen, Thorold W.
通讯作者：
Theunissen, Thorold W.
影响因子：
5.9
作者：
Cinkornpumin, Jessica K.;Kwon, Sin Young;Pastor, William A.
通讯作者：
Pastor, William A.
影响因子：
5.8
作者：
Angerer, Philipp;Haghverdi, Laleh;Buettner, Florian
通讯作者：
Buettner, Florian