let-7 miRNAs can act through notch to regulate human gliogenesis. Stem Cell Reports 2014 Nov 11;3(5):758-73
Date
10/16/2014Pubmed ID
25316189Pubmed Central ID
PMC4235151DOI
10.1016/j.stemcr.2014.08.015Scopus ID
2-s2.0-84922586737 (requires institutional sign-in at Scopus site) 83 CitationsAbstract
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.
Author List
Patterson M, Gaeta X, Loo K, Edwards M, Smale S, Cinkornpumin J, Xie Y, Listgarten J, Azghadi S, Douglass SM, Pellegrini M, Lowry WEAuthor
Michaela Patterson PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Basic Helix-Loop-Helix Transcription FactorsCell Differentiation
Cell Line
Gene Expression Regulation, Developmental
HMGA2 Protein
Humans
Immunohistochemistry
MicroRNAs
Nervous System
Neural Stem Cells
Neurogenesis
Neuroglia
Neurons
Oligodendroglia
Pluripotent Stem Cells
RNA Interference
RNA-Binding Proteins
Receptors, Notch
Repressor Proteins
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
