title: REST/NRSF Knockdown Alters Survival, Lineage Differentiation and Signaling in Human Embryonic Stem Cells.
abstract: REST (RE1 silencing transcription factor), also known as NRSF (neuron-restrictive silencer factor), is a well-known transcriptional repressor of neural genes in non-neural tissues and stem cells. Dysregulation of REST activity is thought to play a role in diverse diseases including epilepsy, cancer, Down's syndrome and Huntington's disease. The role of REST/NRSF in control of human embryonic stem cell (hESC) fate has never been examined. To evaluate the role of REST in hESCs we developed an inducible REST knockdown system and examined both growth and differentiation over short and long term culture. Interestingly, we have found that altering REST levels in multiple hESC lines does not result in loss of self-renewal but instead leads to increased survival. During differentiation, REST knockdown resulted in increased MAPK/ERK and WNT signaling and increased expression of mesendoderm differentiation markers. Therefore we have uncovered a new role for REST in regulation of growth and early differentiation decisions in human embryonic stem cells.
authors.affiliation: Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, 90095, United States of America.
authors.forename: Kaushali
authors.initials: K
authors.lastname: Thakore-Shah
authors.affiliation: California State University, Northridge, CA, 91325, United States of America.
authors.forename: Tasneem
authors.initials: T
authors.lastname: Koleilat
authors.affiliation: California State University, Northridge, CA, 91325, United States of America.
authors.forename: Majib
authors.initials: M
authors.lastname: Jan
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, 90095, United States of America.
authors.forename: Alan
authors.initials: A
authors.lastname: John
authors.affiliation: Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, 90095, United States of America.|Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, 90095, United States of America.|Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, 90095, United States of America.
authors.forename: April D
authors.initials: AD
authors.lastname: Pyle
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D055785:Gene Knockdown Techniques; D000066449:Human Embryonic Stem Cells / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor