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Status |
Public on Jun 26, 2017 |
Title |
Widespread translational remodeling during human neuronal differentiation |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Other
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Summary |
Faithful cellular differentiation requires precise coordination of changes in gene expression. However, the relative contributions of transcriptional and translational regulation during human cellular differentiation are unclear. Here, we induced forebrain neuronal differentiation of human embryonic stem cells (hESCs) and characterized genome-wide RNA and translation levels during neurogenesis. We find that thousands of genes change at the translation level across differentiation without a corresponding change in RNA level. Specifically, we identify mTOR complex 1 signaling as a key driver for elevated translation of translation-related genes in hESCs. In contrast, translational repression in active neurons is mediated by transcript 3′ UTRs, through regulatory sequences. Together, our findings identify a functional role for the dramatic 3′ UTR extensions that occur during brain development, and provide insights to interpret genetic variants in post-transcriptional control factors that influence neurodevelopmental disorders and diseases.
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Overall design |
Forebrain neural cultures differentiated from human embryonic stem cells were isolated and cellular RNA, polysomal RNA, and ribosome protected footprints were deep sequenced.
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Contributor(s) |
Blair JD, Hockemeyer D, Doudna JA, Bateup HS, Floor SN |
Citation(s) |
29141229 |
NIH grant(s) |
Grant ID |
Grant title |
Affiliation |
Name |
R01 NS097823 |
Elucidating the neuropathophysiology of TSC using genetically engineered human neurons |
UNIVERSITY OF CALIFORNIA BERKELEY |
Helen Shirley Bateup |
R01 CA196884 |
Telomerase function in human tumor and stem cell biology |
UNIVERSITY OF CALIFORNIA BERKELEY |
Dirk Hockemeyer |
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Submission date |
Jun 13, 2017 |
Last update date |
May 15, 2019 |
Contact name |
Stephen N. Floor |
E-mail(s) |
stephen.floor@ucsf.edu
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Organization name |
University of California, San Francisco
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Department |
Cell and Tissue Biology
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Lab |
Floor Lab
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Street address |
513 Parnassus Ave, HSW 740
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City |
San Francisco |
State/province |
CA |
ZIP/Postal code |
94143 |
Country |
USA |
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Platforms (1) |
GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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Samples (52)
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Relations |
BioProject |
PRJNA390315 |
SRA |
SRP109126 |