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Series GSE115867 Query DataSets for GSE115867
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
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)
GSM3192176 iPSC_WT_rep1
GSM3192177 iPSC_WT_rep2
GSM3192178 iPSC_CHMP1A_null_rep1
BioProject PRJNA476335
SRA SRP150634

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

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
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Raw data are available in SRA
Processed data are available on Series record

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