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| Status |
Public on Mar 15, 2024 |
| Title |
The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
While hypoxic signaling has been shown to play a role in many cellular processes, its role in metabolism linked extracellular matrix (ECM) organization and downstream processes of cell fate after musculoskeletal injury remains to be determined. Heterotopic ossification (HO) is a debilitating condition where abnormal bone formation occurs within extra-skeletal tissues. Hypoxia and hypoxia-inducible factor 1α (HIF-1α) activation have been shown to promote HO. However, the underlying molecular mechanisms by which the HIF-1α pathway in mesenchymal progenitor cells (MPCs) contributes to pathologic bone formation remain to be elucidated. Here we used a proven mouse injury-induced HO model to investigate the role of HIF-1α on aberrant cell fate. Using single-cell RNA-sequencing (scRNA-Seq), we found that collagen ECM organization is the most highly up-regulated biological process in MPCs. Zeugopod mesenchymal cell-specific deletion of Hif1α (Hoxa11-CreERT2; Hif1afl/fl) significantly mitigated HO in vivo. ScRNA-Seq analysis of these Hoxa11-CreERT2; Hif1afl/fl mice identified the PLOD2/LOX pathway for collagen cross-linking as downstream of the HIF-1α regulation of HO. Importantly, our scRNA-seq data and mechanistic studies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α deletion.
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| Overall design |
To investigate the effects of Hoxa11(+) lineage specific deletion of Hif1a on burn/tenotomy injury-induced heterotopic ossification, cells from tenotomy inury site were isolated at 7 days post-injury for scRNA-seq.
Sample A1,B1: 10 week old male C57BL/6 mice were subjected to the burn/tenotomy procedure. Samples were collected 7 days post-injury
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| Contributor(s) |
Kang H, Pagani CA, Tower R, Levi B |
| Citation(s) |
38472175 |
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| Submission date |
Feb 16, 2024 |
| Last update date |
Aug 17, 2024 |
| Contact name |
Sneha Korlakunta |
| E-mail(s) |
sneha.korlakunta@utsouthwestern.edu
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| Organization name |
UT Southwestern Medical Center
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| Department |
Surgery
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| Lab |
Center for Organogenesis, Regeneration, and Trauma
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| Street address |
6000 Harry Hines Blvd
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| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75235 |
| Country |
USA |
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| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL34328 |
Illumina NovaSeq X (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA1077281 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE255942_RAW.tar |
70.7 Mb |
(http)(custom) |
TAR (of CSV, JPG, JSON, MTX, PNG, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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