title: A distinct microRNA signature for definitive endoderm derived from human embryonic stem cells.
abstract: Human embryonic stem cells (hESCs) have the potential to differentiate into many adult cell types, and they are being explored as a resource for cell replacement therapies for multiple diseases. In order to optimize in vitro differentiation protocols, it will be necessary to elucidate regulatory mechanisms that contribute to lineage specification. MicroRNAs (miRNAs) are emerging as key regulators of hESC differentiation and embryonic development. In this study, we compare miRNA expression profiles between pluripotent hESCs and definitive endoderm (DE), an early step in the pathway toward the pancreatic lineage. Results from microarray analysis showed that DE can be distinguished by its unique miRNA profile, which consists of 37 significantly down-regulated and 17 up-regulated miRNAs in 2 different cell lines and in the presence/absence of feeder layers. Comparison to other hESC-derived lineages showed that most of the highly up-regulated miRNAs are specific to endoderm in early development. Notably, miR-375, which was previously implicated in regulating development and function of later stages of pancreatic development, is highly and specifically up-regulated during DE formation, suggesting that it may have a distinct role very early in development. Examination of potential mRNA targets showed that TIMM8A is repressed by ectopic miR-375 expression in pluripotent hESCs.
authors.affiliation: Pediatric Diabetes Research Center, Stem Cell Program, University of California, San Diego, La Jolla, California, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hinton
authors.forename: Ivka
authors.initials: I
authors.lastname: Afrikanova
authors.forename: Mike
authors.initials: M
authors.lastname: Wilson
authors.forename: Charles C
authors.initials: CC
authors.lastname: King
authors.forename: Brian
authors.initials: B
authors.lastname: Maurer
authors.forename: Gene W
authors.initials: GW
authors.lastname: Yeo
authors.forename: Alberto
authors.initials: A
authors.lastname: Hayek
authors.forename: Amy E
authors.initials: AE
authors.lastname: Pasquinelli
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D004707:Endoderm / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics
chemical_list: D026901:Membrane Transport Proteins; D035683:MicroRNAs; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C118122:TIMM8A protein, human