title: let-7 miRNAs can act through notch to regulate human gliogenesis.
abstract: It is clear that neural differentiation from human pluripotent stem cells generates cells that are developmentally immature. Here, we show that the let-7 plays a functional role in the developmental decision making of human neural progenitors, controlling whether these cells make neurons or glia. Through gain- and loss-of-function studies on both tissue and pluripotent derived cells, our data show that let-7 specifically regulates decision making in this context by regulation of a key chromatin-associated protein, HMGA2. Furthermore, we provide evidence that the let-7/HMGA2 circuit acts on HES5, a NOTCH effector and well-established node that regulates fate decisions in the nervous system. These data link the let-7 circuit to NOTCH signaling and suggest that this interaction serves to regulate human developmental progression.
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine, UCLA, Box 957357, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, UCLA, 621 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
authors.forename: M
authors.initials: M
authors.lastname: Patterson
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine, UCLA, Box 957357, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, UCLA, 621 Charles E. Young Drive East, Los Angeles, CA 90095, USA; Molecular Biology Institute, UCLA, 611 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
authors.forename: X
authors.initials: X
authors.lastname: Gaeta
authors.affiliation: Department of Molecular, Cell and Developmental Biology, UCLA, 621 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
authors.forename: K
authors.initials: K
authors.lastname: Loo
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine, UCLA, Box 957357, Los Angeles, CA 90095, USA.
authors.forename: M
authors.initials: M
authors.lastname: Edwards
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine, UCLA, Box 957357, Los Angeles, CA 90095, USA.
authors.forename: S
authors.initials: S
authors.lastname: Smale
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine, UCLA, Box 957357, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, UCLA, 621 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
authors.forename: J
authors.initials: J
authors.lastname: Cinkornpumin
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine, UCLA, Box 957357, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, UCLA, 621 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Microsoft Research, 1100 Glendon Avenue Suite PH1, Los Angeles, CA 90024, USA.
authors.forename: J
authors.initials: J
authors.lastname: Listgarten
authors.affiliation: Department of Molecular, Cell and Developmental Biology, UCLA, 621 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
authors.forename: S
authors.initials: S
authors.lastname: Azghadi
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine, UCLA, Box 957357, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, UCLA, 621 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Douglass
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine, UCLA, Box 957357, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, UCLA, 621 Charles E. Young Drive East, Los Angeles, CA 90095, USA.
authors.forename: M
authors.initials: M
authors.lastname: Pellegrini
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine, UCLA, Box 957357, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, UCLA, 621 Charles E. Young Drive East, Los Angeles, CA 90095, USA; Molecular Biology Institute, UCLA, 611 Charles E. Young Drive East, Los Angeles, CA 90095, USA. Electronic address: blowry@ucla.edu.
authors.forename: W E
authors.initials: WE
authors.lastname: Lowry
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009420:Nervous System / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D025743:HMGA2 Protein; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; C516326:LIN28B protein, human; C487931:mirnlet7 microRNA, human; C077478:HES5 protein, human