|
|
GEO help: Mouse over screen elements for information. |
|
Status |
Public on Jun 16, 2018 |
Title |
The ESCRT-III protein CHMP1A mediates secretion of sonic hedgehog on a novel class of extracellular vesicles |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
Extracellular vesicles (EVs) enable cell-to-cell communication in the nervous system essential for development and adult function. Endosomal Sorting Complex Required for Transport (ESCRT) complex proteins regulate EV formation and release. Recent work shows loss of function (LOF) mutations in, CHMP1A, which encodes one ESCRT-III member, cause autosomal recessive microcephaly with pontocerebellar hypoplasia in humans (Mochida et al., 2012). Here we show CHMP1A is required for maintenance of progenitors in human cerebral organoids and that mouse Chmp1a is required for progenitor proliferation in cortex and cerebellum and specifically for sonic hedgehog (SHH) mediated proliferation through SHH secretion. CHMP1A mutation reduces intraluminal vesicle (ILV) formation in multivesicular bodies (MVBs), and EV release. SHH protein is present on a subset of EVs marked by a unique set of proteins we call ART-EVs. CHMP1A’s requirement in formation of ART-EVs and other EVs provides a model to elucidate EV functions in multiple brain processes.
|
|
|
Overall design |
Gene expression profiling in a hiPSC WT line and a hiPSC CHMP1A null line. Comparative analysis by RNA-seq in hIPSCs and directed differentiation to cerebral organoids. Treatment with smoothened agonist (SAG) was used for examination of SHH dependent response in WT and CHMP1A null organoids.
|
|
|
Contributor(s) |
Coulter ME, Dorobantu C, Lodewijk GA, Delalande F, Cianferani S, Ganesh V, Smith R, Lim ET, Xu CS, Pang S, Wong ET, Lidov HG, Calicchio ML, Yang E, Gonzalez DM, Schlaeger T, Mochida G, Hess H, Lee W, Lehtinen MK, Kirchhausen T, Haussler D, Jacobs FM, Gaudin R, Walsh CA |
Citation(s) |
30044992 |
Submission date |
Jun 15, 2018 |
Last update date |
Mar 27, 2019 |
Contact name |
Ali S Shariati |
E-mail(s) |
alish@ucsc.edu
|
Organization name |
University of California Santa Cruz
|
Department |
Biomolecular Engineering
|
Lab |
Shariati Lab
|
Street address |
1156 High St
|
City |
Santa Cruz |
State/province |
CA |
ZIP/Postal code |
95064 |
Country |
USA |
|
|
Platforms (2) |
GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
GPL17303 |
Ion Torrent Proton (Homo sapiens) |
|
Samples (16)
|
|
Relations |
BioProject |
PRJNA476335 |
SRA |
SRP150634 |
Supplementary file |
Size |
Download |
File type/resource |
GSE115867_NormalizedCountsOrganoids.txt.gz |
481.5 Kb |
(ftp)(http) |
TXT |
GSE115867_NormalizedCountsiPSC.txt.gz |
668.9 Kb |
(ftp)(http) |
TXT |
GSE115867_RawCountsOrganoids.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
GSE115867_RawCountsiPSC.txt.gz |
328.0 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
|
|
|
|
|