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| Status |
Public on Oct 03, 2022 |
| Title |
Single Cell Spatial Transcriptomics Redefines the Borderzone induced by Myocardial Infarction and Mechanical Injury |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The ischemic borderzone (BZ) is a geographically complex and biologically enigmatic interface separating poorly perfused infarct zones (IZ) from comparatively healthy remote zones (RZ). BZ cellular and molecular mechanisms are not well understood because efforts to dissect it inevitably include RZ and IZ in uncontrolled proportions. Here, we use single-cell/nuclei RNA-sequencing, spatial transcriptomics, and multiplexed RNA fluorescence in situ hybridization (mFISH) to identify BZ cardiomyocytes (CMs) subsets. BZ1 (Nppa+Xirp2-) forms a hundreds-of-microns-thick transitional layer adjacent to RZ, while BZ2 (Nppa+Xirp2+) forms a tens-of-microns-thick layer that the IZ edge. BZ2 CMs have reduced CM cell contact; colocalize with matricellular-protein-expressing myofibroblasts; and upregulate focal adhesion-, sarcomere-, and cytoskeletal-genes. Surprisingly, the transcriptional BZ emerges within an hour of injury and is inducible by non-ischemic fine-needle-trauma. We suggest that mechanical instability and “loss of neighbor” at the BZ edge are the dominant inducers of the BZ transcriptional response.
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| Overall design |
Gene expression profiling of 10x Genomic Chromium single nuclei RNA-Seq or Visium spatial transcriptomics from the left ventricular myocardium or short axis sections of healthy and injured adult male C57BL6 mouse hearts (8-12 weeks). Injuries include MI (permanent ligation of the LAD coronary artery), I/R-30 (30 minutes of ischemia followed by reperfusion), transaortic constriction, isoproterenol injection, and traumatic needle injection.
Please note that the processed data files for GSM6613081, GSM6613087, GSM6613090 have been replaced on May 18, 2023 as the previous files were incomplete (missing spatial data folder and .h5 matrix file).
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| Web link |
https://www.nature.com/articles/s44161-022-00160-3
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| Contributor(s) |
Calcagno DM, Taghdiri N, Ninh VK, Mesfin JM, Toomu A, Sehgal R, Lee J, Liang Y, Duran JM, Adler E, Christman KL, Zhang K, Sheikh F, King KR |
| Citation(s) |
39086770 |
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DM Calcagno, N Taghdiri, VK Ninh, JM Mesfin, A Toomu, R Sehgal, J Lee, Y Liang, JM Duran, E Adler, KL Christman, K Zhang, F Sheikh, Z Fu and KR King. Single-cell and spatial transcriptomics of the infarcted heart define the dynamic onset of the border zone in response to mechanical destabilization. Nat Cardiovasc Res 2022, 1:1039-1055. doi:10.1038/s44161-022-00160-3
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| Submission date |
Oct 01, 2022 |
| Last update date |
Aug 26, 2024 |
| Contact name |
Kevin R King |
| Organization name |
UC San Diego
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| Department |
Medicine and Bioengineering
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| Lab |
King Lab
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| Street address |
9500 Gilman Dr. MC 0412
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
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| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (32)
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| GSM6613062 |
Single nuclei, 1HR MI, biol rep 1 |
| GSM6613063 |
Single nuclei, 1HR MI, biol rep 2 |
| GSM6613064 |
Single nuclei, 4HR MI |
| GSM6613065 |
Single nuclei, Day1 MI, biol rep 1 |
| GSM6613066 |
Single nuclei, Day1 MI, biol rep 2 |
| GSM6613067 |
Single nuclei, Day1 MI, biol rep 3 |
| GSM6613068 |
Single nuclei, Day1 MI, biol rep 4 |
| GSM6613069 |
Single nuclei, Day1 MI, biol rep 5 |
| GSM6613070 |
Single nuclei, Day1 MI, biol rep 6 |
| GSM6613071 |
Single nuclei, Day3 MI, biol rep 1 |
| GSM6613072 |
Single nuclei, Day3 MI, biol rep 2 |
| GSM6613073 |
Single nuclei, Day3 MI, biol rep 3 |
| GSM6613074 |
Single nuclei, Day7 MI, biol rep 1 |
| GSM6613075 |
Single nuclei, Day7 MI, biol rep 2 |
| GSM6613076 |
Single nuclei, Day7 MI, biol rep 3 |
| GSM6613077 |
Visium, Day3 Isoproterenol |
| GSM6613078 |
Visium, 1HR 4HR Day3 Needle Pass, biol rep 1 |
| GSM6613079 |
Visium, Day3 TAC, Day3 Needle pass biol rep 2 |
| GSM6613080 |
Visium, Day 3 Sham biol rep 1, Day3 Needle pass biol rep 3 |
| GSM6613081 |
Visium Day 3 Sham biol rep 2, Day3 Needle pass biol rep 4 |
| GSM6613082 |
Visium, 1HR MI |
| GSM6613083 |
Visium, 4HR MI |
| GSM6613084 |
Visium, Day3 MI biol rep 1 |
| GSM6613085 |
Visium, Day3 MI biol rep 2 |
| GSM6613086 |
Visium, Day3 MI biol rep 3 |
| GSM6613087 |
Visium, Day7 MI biol rep 1 |
| GSM6613088 |
Visium, Day7 MI biol rep 2 |
| GSM6613089 |
Visium, Day7 MI biol rep 3 |
| GSM6613090 |
Visium, STEMI |
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| Relations |
| BioProject |
PRJNA886090 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE214611_RAW.tar |
2.7 Gb |
(http)(custom) |
TAR (of TAR, ZIP) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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