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| Status |
Public on Dec 27, 2022 |
| Title |
Enhancing wound inducible adaptive fibroblast reprogramming overcomes diabetic healing impairment |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Adaptive cellular reprogramming is an emerging field to study promotion of a host’s intrinsic healing strategies through changing one somatic cell type into another state or fate; tissue injury is known to enhance such cell conversions. Here we identify a molecular pathway in injured skin, whereby a subset of dermal fibroblasts displays a novel vasculogenic state change with gain in vasculogenic transcripts and endothelial cell-like functions without losing core fibroblast lineage fate phenotypic, functional, and transcriptional characteristics. Removal of microRNA suppression of FLI1 transcription in fibroblasts results in upregulation of a cascade of vasculogenic molecules that heralds the vasculogenic state change in some fibroblasts. FLI1 dependent vasculogenic fibroblast subset emergence in injured skin is blunted in poorly healing skin wounds of diabetic animals but can be restored through topical tissue nanotransfection of a single anti-microRNA oligonucleotide, to rescue tissue perfusion and wound healing. Augmenting a physiologic tissue injury adaptive response mechanism that produces vasculogenic fibroblasts opens new avenues for therapeutic tissue vascularization of ischemic conditions.
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| Overall design |
To define the transcriptional changes during HADF reprogramming, single cell RNA sequencing (scRNA-seq) was performed at days 1, 3, 5 and 7 following miRIDIAN microRNA hsa-miR-200b-3p hairpin inhibitor (MI) transfection. To account for the effect of transfection, additional samples were analyzed using control transfection (miRIDIAN microRNA hairpin inhibitor negative control; control inhibitor, CI) at two different time points (d1 and d7 post-transfection).
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| Web link |
https://www.nature.com/articles/s41467-023-36665-z
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| Contributor(s) |
Sen CK, Singh K, Abouhashem AS, Yoder MC, Roy S, Mohanty S, Srivastava R |
| Citation(s) |
36854749 |
| |
| Submission date |
Feb 24, 2021 |
| Last update date |
May 05, 2024 |
| Contact name |
Chandan K Sen |
| Organization name |
University of Pittsburgh
|
| Department |
Surgery
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| Lab |
McGowan Institute for Reg Med
|
| Street address |
450 Technology Drive
|
| City |
Pittsburgh |
| State/province |
Pennsylvania |
| ZIP/Postal code |
15219 |
| Country |
USA |
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| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (7)
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| Relations |
| BioProject |
PRJNA704577 |
| SRA |
SRP307929 |
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