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| Status |
Public on Jul 11, 2024 |
| Title |
BMP-dependent cellular dynamics during cranial suture establishment in zebrafish |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Cranial sutures separate neighboring skull bones and contain skeletal stem cells that drive bone growth. A key question is how osteogenic activity is controlled to promote bone growth while preventing aberrant bone fusions during skull expansion. Here we integrate single-cell transcriptomics, in vivo expression validation, photoconversion-based lineage tracing, and a zebrafish craniosynostosis model to uncover key developmental transitions regulating bone formation during skull expansion. In addition to conservation of meninges and osteoblast lineage cells between zebrafish and mouse, single-cell transcriptomic analysis of the zebrafish skull reveals distinct subpopulations of suture mesenchyme that undergo transcriptomic changes during suture establishment. While lineage tracing with an osteoblast-specific nlsEOS reporter shows that bone formation largely occurs at suture edges, a subset of mesenchyme cells in the mid-suture region upregulate a suite of genes including BMP antagonists (e.g. grem1a) and pro-angiogenic factors. Further, lineage tracing with grem1a:nlsEOS reveals that this mid-suture subpopulation is largely non-osteogenic. In twist1b; tcf12 mutant zebrafish, a model for the coronal synostosis of Saethre-Chotzen Syndrome, reduction of grem1a+ mid-suture cells correlates with misregulated bone formation and reduced blood vessels at the coronal suture. In addition, combinatorial mutation of BMP antagonists enriched in the mid-suture subpopulation results in increased BMP signaling in the suture, misregulated bone formation, and abnormal suture morphology. These data support roles of a subset of mid-suture mesenchyme in locally promoting BMP antagonism that ensures proper suture morphology.
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| Overall design |
Dissected calvaria of zebrafish were dissociated from juvenvile and adult zebrafish and live cells were identified by sorting for the absence of fluoresence (sp7:GFP or ecad:YFP) and the absence of DAPI using Fluorescence-activated cell sorting (FACS). Sorted cells were processed using 10X Genomics
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| Contributor(s) |
Farmer DT, Arata CE, Crump G |
| Citation(s) |
39138165 |
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| Submission date |
Jan 18, 2023 |
| Last update date |
Sep 11, 2024 |
| Contact name |
Claire Arata |
| E-mail(s) |
carata@usc.edu, clairearata@gmail.com
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| Organization name |
University of Southern California
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| Department |
Stem Cell
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| Lab |
Crump Lab
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| Street address |
1425 San Pablo St
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90033 |
| Country |
USA |
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| Platforms (2) |
| GPL20828 |
Illumina NextSeq 500 (Danio rerio) |
| GPL23274 |
Illumina HiSeq 3000 (Danio rerio) |
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| Samples (4)
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| GSM6940302 |
9-11 mm Juvenile Calvaria, ecadYFPdepleted, DAPI neg |
| GSM6940303 |
9-11 mm Juvenile Calvaria, sp7GFPdepleted, DAPI neg |
| GSM6940304 |
22-25 mm Adult Calvaria, ecadYFPdepleted, DAPI neg |
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| Relations |
| BioProject |
PRJNA925134 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE223147_RAW.tar |
68.2 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
| GSE223147_zebrafishcalvaria_allcells.rds.gz |
1.5 Gb |
(ftp)(http) |
RDS |
| GSE223147_zebrafishcalvaria_connectivetissue.rds.gz |
585.8 Mb |
(ftp)(http) |
RDS |
| GSE223147_zebrafishcalvaria_mesenchymeosteoblasts.rds.gz |
93.2 Mb |
(ftp)(http) |
RDS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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