Cross James C, Anson-Cartwright Lynn, Scott Ian C
Department of Biochemistry & Molecular Biology, University of Calgary Faculty of Medicine, Alberta, Canada.
Recent Prog Horm Res. 2002;57:221-34. doi: 10.1210/rp.57.1.221.
The placenta has been the subject of extensive basic research efforts in two distinct fields. The developmental biology of placenta has been studied because it is the first organ to develop during embryogenesis and because a number of different gene mutations in mice result in embryonic lethality due to placental defects. The trophoblast cell lineage is relatively simple such that only two major, terminally differentiated cell types appear: an "invasive trophoblast" cell subtype such as extravillous cytotrophoblast cells in humans and trophoblast giant cells in mice, and a "transport trophoblast" cell subtype that is a syncytium (syncytiotrophoblast) in humans and mice. These two cell types also have been the focus of endocrinologists because they are the source of major placental hormones. Understanding the transcriptional regulation of placental hormone genes has given insights into the control of specificity of gene expression. Because most placental hormones are produced by very specific trophoblast cell subtypes, the transcriptional details promise to give insights into cell-subtype specification. The fields of developmental biology and molecular endocrinology appear to be meeting on this common ground with the recent discovery of key transcription factors. Specifically, the basic helix-loop-helix (bHLH) transcription factor Hand1 is essential for differentiation of trophoblast giant cells in mice and also regulates the promoter for the giant cell-specific hormone, placental lactogen I gene (Pl1). In contrast, formation of syncytiotrophoblast cells in mice is controlled by a distinct genetic pathway that is governed by the Gcm1 transcription factor, a homologue of the Drosophila glial cells missing gene. Human GCM I has been shown to regulate the activity of the placental-specific enhancer of the aromatase gene (CYP19), which is specifically expressed in syncytiotrophoblast. Together, these findings imply that some key transcription factors have the dual functions of controlling both critical cell fate decisions in the trophoblast cell lineage and later the transcription of cell subtype-specific genes unrelated to development.
胎盘一直是两个不同领域广泛基础研究的对象。胎盘的发育生物学之所以受到研究，是因为它是胚胎发育过程中第一个发育的器官，还因为小鼠中的一些不同基因突变会因胎盘缺陷导致胚胎致死。滋养层细胞谱系相对简单，仅出现两种主要的终末分化细胞类型：一种“侵袭性滋养层”细胞亚型，如人类的绒毛外细胞滋养层细胞和小鼠的滋养层巨细胞，以及一种“运输滋养层”细胞亚型，在人类和小鼠中均为合体滋养层（合体滋养层细胞）。这两种细胞类型也是内分泌学家关注的焦点，因为它们是主要胎盘激素的来源。了解胎盘激素基因的转录调控有助于深入了解基因表达特异性的控制。由于大多数胎盘激素由非常特定的滋养层细胞亚型产生，转录细节有望为细胞亚型特异性提供深入见解。随着关键转录因子的最新发现，发育生物学和分子内分泌学领域似乎在这个共同基础上交汇。具体而言，基本螺旋-环-螺旋（bHLH）转录因子Hand1对小鼠滋养层巨细胞的分化至关重要，还调控巨细胞特异性激素胎盘催乳素I基因（Pl1）的启动子。相比之下，小鼠合体滋养层细胞的形成由一个独特的遗传途径控制，该途径由Gcm1转录因子调控，它是果蝇神经胶质细胞缺失基因的同源物。已证明人类GCM I可调节芳香化酶基因（CYP19）胎盘特异性增强子的活性，该基因在合体滋养层中特异性表达。总之，这些发现表明一些关键转录因子具有双重功能，既能控制滋养层细胞谱系中的关键细胞命运决定，又能控制与发育无关的细胞亚型特异性基因的转录。
