title: The imprinted polycomb group gene Sfmbt2 is required for trophoblast maintenance and placenta development.
abstract: Imprinted genes play important roles in placenta development and function. Parthenogenetic embryos, deficient in paternally expressed imprinted genes, lack extra-embryonic tissues of the trophoblast lineage. Parthenogenetic trophoblast stem cells (TSCs) are extremely difficult to derive, suggesting that an imprinted gene(s) is necessary for TSC establishment or maintenance. In a candidate study, we were able to narrow the list to one known paternally expressed gene, Sfmbt2. We show that mouse embryos inheriting a paternal Sfmbt2 gene trap null allele have severely reduced placentae and die before E12.5 due to reduction of all trophoblast cell types. We infected early embryos with lentivirus vectors expressing anti-Sfmbt2 shRNAs and found that TSC derivation was significantly reduced. Together, these observations support the hypothesis that loss of SFMBT2 results in defects in maintenance of trophoblast cell types necessary for development of the extra-embryonic tissues, the placenta in particular.
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, 25 Harbord Sreet, Toronto, Ontario M5S 3G5, Canada.
authors.forename: Kamelia
authors.initials: K
authors.lastname: Miri
authors.forename: Keith
authors.initials: K
authors.lastname: Latham
authors.forename: Barbara
authors.initials: B
authors.lastname: Panning
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Zhong
authors.forename: Angela
authors.initials: A
authors.lastname: Andersen
authors.forename: Susannah
authors.initials: S
authors.lastname: Varmuza
mesh_terms: D000483:Alleles; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D005260:Female; D005306:Fertilization / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D018392:Genomic Imprinting / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D040582:Inheritance Patterns / Q000235:genetics; D051379:Mice; D010312:Parthenogenesis / Q000235:genetics; D010929:Placentation / Q000235:genetics*; D063146:Polycomb-Group Proteins / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism; D049951:X Chromosome Inactivation / Q000235:genetics
chemical_list: D063146:Polycomb-Group Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C527638:Sfmbt2 protein, mouse; D014157:Transcription Factors
keywords: Loss of imprinting; Mouse; Parthenogenesis; Placenta; Polycomb group protein; Sfmbt2; Trophoblast stem cell