c-Met-Dependent Multipotent Labyrinth Trophoblast Progenitors Establish Placental Exchange Interface

• DOI: 10.1016/j.devcel.2013.10.019
• Publication Date: 2013-11-25T15:33:51Z
• Authors: Masaya Ueno; Lydia K. Lee; Akanksha Chhabra; Yeon Joo Kim; Rajkumar Sasidharan; Ben Van Handel; Ying Wang; Masakazu Kamata; Paniz Kamran; Konstantina-Ioann...; Reza Ardehali; Meisheng Jiang; Hanna K.A. Mikkola
• Keywords: Placenta; Fluorescent Antibody Technique; Real-Time Polymerase Chain Reaction; Medical and Health Sciences; Mice; 03 medical and health sciences; Pregnancy; Animals; RNA, Messenger; Maternal-Fetal Exchange; Cell Proliferation; Oligonucleotide Array Sequence Analysis; 0303 health sciences; Fetal Growth Retardation; Reverse Transcriptase Polymerase Chain Reaction; Gene Expression Profiling; Gene Expression Regulation, Developmental; Cell Differentiation; Biological Sciences; Proto-Oncogene Proteins c-met; Liver; Ear, Inner; Female; Biomarkers; Developmental Biology

The placenta provides the interface for gas and nutrient exchange between the mother and the fetus. Despite its critical function in sustaining pregnancy, the stem/progenitor cell hierarchy and molecular mechanisms responsible for the development of the placental exchange interface are poorly understood. We identified an Epcam(hi) labyrinth trophoblast progenitor (LaTP) in mouse placenta that at a clonal level generates all labyrinth trophoblast subtypes, syncytiotrophoblasts I and II, and sinusoidal trophoblast giant cells. Moreover, we discovered that hepatocyte growth factor/c-Met signaling is required for sustaining proliferation of LaTP during midgestation. Loss of trophoblast c-Met also disrupted terminal differentiation and polarization of syncytiotrophoblasts, leading to intrauterine fetal growth restriction, fetal liver hypocellularity, and demise. Identification of this c-Met-dependent multipotent LaTP provides a landmark in the poorly defined placental stem/progenitor cell hierarchy and may help us understand pregnancy complications caused by a defective placental exchange.