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Status |
Public on Jan 16, 2025 |
Title |
IFIT1 Knockdown Mitigates Translational Suppression, Enhancing Myogenic Differentiation and Revitalizing Mesenchymal Stem Cell Therapy for Myocardial Infarction [II] |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Early transplantation of mesenchymal stem cells (MSCs) showed promise in rescuing cardiac function and alleviating ventricular remodeling post-myocardial infarction (MI) while regulatory T cells (Treg) either. However, the crosstalk between them remains fully elusive. To explore mechanisms optimizing MSC therapy from Treg immunoregulatory and develop potential therapeutic targets, adipose-derived stem cells (ADSCs), an easily accessible MSC, were applied. The Treg depletion diminished the cardioprotective effects of ADSCs, causing both systolic dysfunction and cardiac fibrosis. Tregs promoted ADSC retention by proliferation and migration activation with further myogenic differentiation. RNA-sequencing analysis revealed Treg co-culture induced a myogenic differentiation mRNA profile in ADSCs, significantly downregulating Ifit1. IFIT1 downregulation resulted in cardiomyocyte-like differentiation in ADSCs, evidenced by increased myogenic markers and spontaneous beating. Mechanistically, IFIT1 knockdown provoked upregulation of E2F1 protein without altering E2f1 mRNA levels. IFIT1 specifically bound to E2f1 mRNA to inhibit translation, reducing polysomes while knockdown introduced myogenic translational profile. The rAAV9-sh-Ifit1 injection restored systolic dysfunction, reduced fibrosis, and attenuated cardiac hypertrophy. This study uncovered a novel mechanism whereas Tregs potentiated the therapeutic efficacy of ADSCs in MI by downregulating IFIT1, thereby promoting E2f1 translation and myogenic differentiation, offering a potential target to improve cardiac repair strategies.
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Overall design |
RNA sequencing analysis was performed on Scrasmbled ADSCs (TR-Sc-1,TR-Sc-2,TR-Sc-3) and sh-Ifit1 ADSC (TR-KD-1,TR-KD-2,TR-KD-3) (n = 3/group).
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Contributor(s) |
Wu L, Pang Y, Xia J, Zhang S, Zhu J, Hou L |
Citation missing |
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Submission date |
Jan 08, 2025 |
Last update date |
Jan 16, 2025 |
Contact name |
Lei Hou |
E-mail(s) |
dr_houlei@shsmu.edu.cn
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Phone |
+8618117283090
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Organization name |
Songjiang Hospital and Songjiang Research Institute, School of Medicine, Shanghai Jiao Tong University
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Department |
Department of Cardiology
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Street address |
746 Zhongshan Middle Road
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City |
Shanghai |
State/province |
Shanghai |
ZIP/Postal code |
201699 |
Country |
China |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (6)
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Relations |
BioProject |
PRJNA1207983 |
Supplementary file |
Size |
Download |
File type/resource |
GSE286132_FPKM_shifit1ADSC.txt.gz |
3.6 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
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