Lee Bum-Kyu, Kim Jonghwan
Department of Biomedical Sciences, Cancer Research Center, University at Albany-State University of New York, Rensselaer, NY, United States.
Department of Molecular Biosciences, Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, United States.
Front Cell Dev Biol. 2021 Jun 2;9:673065. doi: 10.3389/fcell.2021.673065. eCollection 2021.
The placenta is a temporary but pivotal organ for human pregnancy. It consists of multiple specialized trophoblast cell types originating from the trophectoderm of the blastocyst stage of the embryo. While impaired trophoblast differentiation results in pregnancy disorders affecting both mother and fetus, the molecular mechanisms underlying early human placenta development have been poorly understood, partially due to the limited access to developing human placentas and the lack of suitable human trophoblast models. Recent success in establishing human trophoblast stem cells and other human trophoblast models with their differentiation protocols into more specialized cell types, such as syncytiotrophoblast and extravillous trophoblast, has provided a tremendous opportunity to understand early human placenta development. Unfortunately, while high-throughput research methods and omics tools have addressed numerous molecular-level questions in various research fields, these tools have not been widely applied to the above-mentioned human trophoblast models. This review aims to provide an overview of various omics approaches that can be utilized in the study of human placenta models by exemplifying some important lessons obtained from omics studies of mouse model systems and introducing recently available human trophoblast model systems. We also highlight some key unknown questions that might be addressed by such techniques. Integrating high-throughput omics approaches and human model systems will facilitate our understanding of molecular-level regulatory mechanisms underlying early human placenta development as well as placenta-associated complications.
胎盘是人类妊娠期间一个临时性但却至关重要的器官。它由多种源自胚胎囊胚期滋养外胚层的特化滋养层细胞类型组成。虽然滋养层细胞分化受损会导致影响母婴的妊娠疾病,但早期人类胎盘发育的分子机制一直未得到充分理解,部分原因是获取发育中的人类胎盘存在限制,且缺乏合适的人类滋养层模型。最近在建立人类滋养层干细胞和其他人类滋养层模型以及将它们分化为更特化细胞类型(如合体滋养层和绒毛外滋养层)的方案方面取得的成功,为理解早期人类胎盘发育提供了巨大机遇。不幸的是,尽管高通量研究方法和组学工具已经解决了各个研究领域中众多分子水平的问题,但这些工具尚未广泛应用于上述人类滋养层模型。本综述旨在通过举例说明从小鼠模型系统的组学研究中获得的一些重要经验教训,并介绍最近可用的人类滋养层模型系统,概述可用于人类胎盘模型研究的各种组学方法。我们还强调了一些可能通过此类技术解决的关键未知问题。整合高通量组学方法和人类模型系统将有助于我们理解早期人类胎盘发育以及胎盘相关并发症背后的分子水平调控机制。