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Series GSE192616 Query DataSets for GSE192616
Status Public on Jul 15, 2023
Title Multi-omics and 3D-imaging reveal bone heterogeneity and unique calvaria cells in neuroinflammation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The bone marrow in the skull is important for shaping immune responses in the brain and meninges, but its molecular makeup in comparison to other bones in mice and humans remains unclear. Here, we show that the skull has the most distinct transcriptomic profile compared to other bones in states of health and injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveal that the skull marrow is the most distinct, with differentially expressed neutrophil-related pathways and a unique synaptic protein signature. 3D imaging demonstrates the structural and cellular details of human skull-meninges connections compared to veins. Lastly, using TSPO-PET imaging, we show that the skull bone marrow reflects inflammatory brain responses with a disease-specific spatial distribution in patients with various neurological disorders. The unique molecular profile, anatomical, and functional connections of the skull show its potential as a new site for diagnosing, monitoring, and treating brain diseases.
 
Overall design A single-cell RNA sequencing experiment was conducted using 10x Genomics technology on samples from three distinct groups, which included six bones, meninges, and the brain. The study comprised three groups: those that underwent MCAo surgery, those that underwent sham surgery, and a group of naive animals. Each sample consisted of cells pooled from three animals, with a total of 32 samples utilized. The MCAo surgery group contributed 2 samples, each consisting of cells pooled from 3 different animals. The sham and naive groups served as control groups. In addition to the single-cell RNA sequencing, bulk RNA sequencing experiments were conducted using the Illumina ligation stranded mRNA preparation kit. These experiments involved samples from the six bones under the three conditions (naive, sham, and MCAo). Separate measurements were taken for 4-6 animals per condition, yielding a total of 95 samples. Furthermore, bulk RNA sequencing was carried out using Smart-seq2 for mini-bulks of about 50 CD45+/Cd11b+ sorted immune cells each from the skull and femur. These samples were taken from wildtype animals (5 in total) and 5xFAD animals (3 in total), amassing 168 samples overall, with approximately 20 samples per animal.
 
Contributor(s) Kolabas ZI, Kuemmerle LB, Perneczky R, Förstera B, Ulukaya S, Ali M, Kapoor S, Bartos LM, Büttner M, Caliskan OS, Rong Z, Mai H, Höher L, Jeridi D, Molbay M, Khalin I, Deligiannis IK, Negwer M, Roberts K, Simats A, Carofiglio O, Todorov MI, Horvath I, Ozturk F, Hummel S, Biechele G, Zatcepin A, Unterrainer M, Gnörich J, Roodselaar J, Shrouder J, Khosravani P, Tast B, Richter L, Díaz-Marugan L, Kaltenecker D, Lux L, Chen Y, Zhao S, Rauchmann B, Sterr M, Kunze I, Stanic K, Besson-Girard S, Katzdobler S, Palleis C, Schädler J, Paetzold JC, Hauser AE, Gokce O, Lickert H, Steinke H, Benakis C, Braun C, Martinez-Jimenez CP, Buerger K, Albert NL, Höglinger G, Levin J, Haass C, Kopczak A, Dichgans M, Havla J, Kümpfel T, Kerschensteiner M, Schifferer M, Simons M, Liesz A, Krahmer N, Bayraktar OA, Franzmeier N, Plesnila N, Erener S, Puelles VG, Delbridge C, Singh Bhatia H, Hellal F, Elsner M, Bechmann I, Ondruschka B, Brendel M, Theis FJ, Erturk A
Citation(s) 37562402
Submission date Dec 26, 2021
Last update date Oct 23, 2023
Contact name Louis Kuemmerle
Organization name Helmholtz Centre Munich
Street address Ingolstädter Landstraße 1
City Munich
ZIP/Postal code 85764
Country Germany
 
Platforms (2)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (295)
GSM5753457 scRNAseq, mouse, Calvaria, MCAo, rep1
GSM5753458 scRNAseq, mouse, Pelvis, MCAo, rep1
GSM5753459 scRNAseq, mouse, Femur, MCAo, rep1
Relations
BioProject PRJNA792403
SRA SRP352496

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

Supplementary file Size Download File type/resource
GSE192616_5xFAD_adata.h5ad.gz 4.3 Mb (ftp)(http) H5AD
GSE192616_5xFAD_adata_raw.h5ad.gz 2.3 Mb (ftp)(http) H5AD
GSE192616_RAW.tar 798.4 Mb (http)(custom) TAR (of TAB, TAR)
GSE192616_bulk_rna_raw_counts.tsv.gz 5.2 Mb (ftp)(http) TSV
GSE192616_sc_adata_march22h.h5ad.gz 22.2 Mb (ftp)(http) H5AD
GSE192616_sc_adata_oct22m.h5ad.gz 1.2 Gb (ftp)(http) H5AD
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record
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