title: c-Met-dependent multipotent labyrinth trophoblast progenitors establish placental exchange interface.
abstract: 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.
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Masaya
authors.initials: M
authors.lastname: Ueno
authors.forename: Lydia K
authors.initials: LK
authors.lastname: Lee
authors.forename: Akanksha
authors.initials: A
authors.lastname: Chhabra
authors.forename: Yeon Joo
authors.initials: YJ
authors.lastname: Kim
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Sasidharan
authors.forename: Ben
authors.initials: B
authors.lastname: Van Handel
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kamata
authors.forename: Paniz
authors.initials: P
authors.lastname: Kamran
authors.forename: Konstantina-Ioanna
authors.initials: KI
authors.lastname: Sereti
authors.forename: Reza
authors.initials: R
authors.lastname: Ardehali
authors.forename: Meisheng
authors.initials: M
authors.lastname: Jiang
authors.forename: Hanna K A
authors.initials: HK
authors.lastname: Mikkola
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D007758:Ear, Inner / Q000166:cytology* / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008431:Maternal-Fetal Exchange; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000166:cytology* / Q000378:metabolism; D011247:Pregnancy; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D019859:Proto-Oncogene Proteins c-met