Atsushi Suzuki, Angel Raya, Yasuhiko Kawakami, Masanobu Morita, Takaaki Matsui, Kinichi Nakashima, Fred H Gage, Concepción Rodríguez-Esteban, Juan Carlos Izpisúa Belmonte
{"title":"Maintenance of embryonic stem cell pluripotency by Nanog-mediated reversal of mesoderm specification.","authors":"Atsushi Suzuki, Angel Raya, Yasuhiko Kawakami, Masanobu Morita, Takaaki Matsui, Kinichi Nakashima, Fred H Gage, Concepción Rodríguez-Esteban, Juan Carlos Izpisúa Belmonte","doi":"10.1038/ncpcardio0442","DOIUrl":null,"url":null,"abstract":"<p><p>Embryonic stem cells (ESCs) can be propagated indefinitely in culture, while retaining the ability to differentiate into any cell type in the organism. The molecular and cellular mechanisms underlying ESC pluripotency are, however, poorly understood. We characterize a population of early mesoderm-specified (EM) progenitors that is generated from mouse ESCs by bone morphogenetic protein stimulation. We further show that pluripotent ESCs are actively regenerated from EM progenitors by the action of the divergent homeodomain-containing protein Nanog, which, in turn, is upregulated in EM progenitors by the combined action of leukemia inhibitory factor and the early mesoderm transcription factor T/Brachyury. These findings uncover specific roles of leukemia inhibitory factor, Nanog, and bone morphogenetic protein in the self-renewal of ESCs and provide novel insights into the cellular bases of ESC pluripotency.</p>","PeriodicalId":51263,"journal":{"name":"Nature Clinical Practice. Cardiovascular Medicine","volume":"3 Suppl 1 ","pages":"S114-22"},"PeriodicalIF":0.0000,"publicationDate":"2006-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/ncpcardio0442","citationCount":"75","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Clinical Practice. Cardiovascular Medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1038/ncpcardio0442","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 75
Abstract
Embryonic stem cells (ESCs) can be propagated indefinitely in culture, while retaining the ability to differentiate into any cell type in the organism. The molecular and cellular mechanisms underlying ESC pluripotency are, however, poorly understood. We characterize a population of early mesoderm-specified (EM) progenitors that is generated from mouse ESCs by bone morphogenetic protein stimulation. We further show that pluripotent ESCs are actively regenerated from EM progenitors by the action of the divergent homeodomain-containing protein Nanog, which, in turn, is upregulated in EM progenitors by the combined action of leukemia inhibitory factor and the early mesoderm transcription factor T/Brachyury. These findings uncover specific roles of leukemia inhibitory factor, Nanog, and bone morphogenetic protein in the self-renewal of ESCs and provide novel insights into the cellular bases of ESC pluripotency.