DNA Methylation Analysis Reveals Distinct Patterns in Satellite Cell–Derived Myogenic Progenitor Cells of Subjects with Spastic Cerebral Palsy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subject Enrollment
2.2. Satellite Cell Isolation
2.3. DNA Extraction, Library Preparation, and Sequencing
2.4. Methylation Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Sample | Diagnosis | Age | Sex | GMFCS | Tissue Source |
---|---|---|---|---|---|
CN1 | Spondylolysis | 16.6 | M | N/A | Spinalis |
CN2 | Torn ACL | 12.6 | M | N/A | Semitendinosus |
CN3 | Idiopathic scoliosis | 12.1 | F | N/A | Spinalis |
CN4 | Torn ACL | 12.7 | F | N/A | Semitendinosus |
CN5 | Idiopathic scoliosis | 15.1 | M | N/A | Spinalis |
CN6 | Idiopathic scoliosis | 14.3 | F | N/A | Spinalis |
CP1 | Spastic CP | 15.6 | M | 5 | Vastus lateralis |
CP2 | Spastic CP | 19.1 | M | 5 | Adductor longus |
CP3 | Spastic CP | 12.6 | M | 4 | Rectus femoris |
CP4 | Spastic CP | 13.8 | F | 2 | Rectus femoris |
CP5 | Spastic CP | 19.0 | F | 5 | Spinalis |
CP6 | Spastic CP | 12.8 | F | 5 | Spinalis |
Position | MB LogFC | MB FDR Corrected p-Value | MT LogFC | MT FDR Corrected p-Value | Gene |
---|---|---|---|---|---|
chr2.0003882321 | 0.88 | 2.29 × 10−2 | 0.90 | 2.40 × 10−2 | |
chr2.0029850455 | 1.24 | 6.74 × 10−4 | 1.32 | 1.11 × 10−5 | ALK |
chr2.0033057636 | −0.84 | 3.40 × 10−3 | −0.85 | 1.94 × 10−2 | LINC00486 |
chr2.0035092870 | −1.09 | 1.00 × 10−2 | −1.19 | 8.26 × 10−5 | AC012593.1 |
chr2.0056193463 | 1.32 | 1.79 × 10−3 | 1.55 | 1.22 × 10−6 | RP11—481J13.1, AC011306.2 |
chr2.0223166989 | 0.87 | 4.07 × 10−2 | 0.90 | 4.80 × 10−2 | CCDC140 |
chr2.0235215325 | −1.05 | 6.08 × 10−4 | −1.08 | 6.49 × 10−4 | |
chr3.0053784559 | 0.91 | 1.58 × 10−2 | 1.14 | 8.96 × 10−4 | CACNA1D |
chr3.0060919598 | −0.85 | 1.89 × 10−3 | −0.86 | 3.09 × 10−2 | FHIT |
chr3.0119863345 | 1.28 | 2.04 × 10−3 | 1.48 | 1.19 × 10−5 | GPR156 |
chr3.0119990864 | −1.14 | 2.05 × 10−3 | −1.01 | 4.01 × 10−2 | GPR156 |
chr3.0127606140 | −1.40 | 1.26 × 10−4 | −1.12 | 6.36 × 10−3 | |
chr3.0182124231 | −1.14 | 3.82 × 10−2 | −1.15 | 5.10 × 10−3 | |
chr3.0189791239 | −1.34 | 1.56 × 10−2 | −1.13 | 5.00 × 10−2 | LEPREL1 |
chr3.0196595774 | −1.37 | 3.54 × 10−2 | −1.33 | 1.44 × 10−2 | SENP5 |
chr4.0101719592 | −1.04 | 4.74 × 10−5 | −1.15 | 1.77 × 10−7 | EMCN |
chr5.0011534641 | 0.90 | 2.48 × 10−2 | 1.05 | 7.82 × 10−3 | CTNND2 |
chr5.0039219698 | 1.22 | 3.91 × 10−2 | 1.37 | 2.24 × 10−2 | FYB |
chr5.0164483805 | −0.92 | 2.51 × 10−2 | −1.11 | 1.05 × 10−3 | CTC—340A15.2 |
chr5.0166472226 | −1.03 | 1.03 × 10−2 | −1.16 | 4.86 × 10−4 | |
chr6.0008948266 | 1.16 | 2.27 × 10−2 | 1.24 | 2.52 × 10−3 | |
chr6.0016145414 | −1.17 | 2.94 × 10−4 | −1.24 | 9.54 × 10−5 | MYLIP |
chr6.0019413218 | 0.81 | 2.95 × 10−3 | 0.86 | 1.70 × 10−2 | |
chr6.0031008851 | 0.96 | 2.29 × 10−2 | 1.01 | 1.56 × 10−2 | RASSF3 |
chr6.0154640863 | 1.37 | 9.68 × 10−3 | 1.34 | 3.64 × 10−3 | IPCEF1 |
chr6.0161063597 | −2.29 | 3.71 × 10−3 | −1.62 | 2.31 × 10−2 | LPA |
chr7.0016768868 | −0.75 | 1.18 × 10−2 | −1.03 | 1.03 × 10−5 | |
chr7.0044621160 | 0.91 | 1.71 × 10−2 | 0.97 | 4.26 × 10−2 | TMED4 |
chr7.0147581299 | −0.68 | 3.30 × 10−2 | −0.83 | 3.24 × 10−2 | CNTNAP2 |
chr11.0123045794 | −1.36 | 1.13 × 10−3 | −1.54 | 2.08 × 10−6 | CLMP |
chr11.0129565594 | 1.28 | 1.59 × 10−2 | 1.68 | 1.23 × 10−4 | |
chr12.0003241735 | 1.19 | 4.26 × 10−3 | 1.04 | 3.25 × 10−2 | TSPAN9 |
chr12.0026672531 | 1.00 | 4.67 × 10−2 | 1.28 | 1.68 × 10−2 | ITPR2 |
chr12.0048360477 | −1.69 | 3.13 × 10−4 | −1.10 | 4.25 × 10−2 | TMEM106C |
chr12.0054366343 | 0.87 | 4.94 × 10−2 | 1.07 | 3.53 × 10−2 | HOTAIR |
chr12.0055783991 | 1.19 | 4.36 × 10−2 | 1.29 | 2.11 × 10−2 | |
chr12.0083436417 | 1.62 | 4.94 × 10−3 | 2.14 | 6.72 × 10−5 | TMTC2 |
chr12.0114887843 | 1.42 | 1.84 × 10−4 | 0.62 | 4.91 × 10−2 | |
chr12.0116068191 | −1.32 | 1.42 × 10−2 | −1.58 | 5.07 × 10−6 | RP11—1028N23.4 |
chr12.0128167651 | 1.13 | 3.28 × 10−2 | 1.57 | 8.87 × 1014 | |
chr12.0131689822 | 1.29 | 2.19 × 10−2 | 1.74 | 5.09 × 10−5 | RP11—638F5.1 |
chr13.0021286449 | −1.10 | 4.87 × 10−2 | −1.33 | 2.22 × 10−2 | IL17D |
chr13.0027424109 | 1.51 | 1.23 × 10−2 | 1.56 | 5.47 × 10−4 | |
chr13.0033220266 | −1.24 | 5.87 × 10−3 | −1.31 | 2.18 × 10−3 | PDS5B |
chr13.0047191668 | −1.30 | 6.51 × 10−3 | −1.34 | 6.36 × 10−3 | LRCH1 |
chr13.0093896533 | 1.50 | 2.96 × 10−2 | 2.41 | 2.86 × 10−5 | GPC6 |
chr13.0099687193 | 1.01 | 3.54 × 10−2 | 1.06 | 4.85 × 10−2 | DOCK9 |
chr13.0107176083 | −1.69 | 7.74 × 10−3 | −1.68 | 1.29 × 10−2 | EFNB2 |
chr13.0109856377 | −1.48 | 4.00 × 10−2 | −1.52 | 6.19 × 10−3 | MYO16 |
chr14.0021177142 | −1.22 | 3.13 × 10−4 | −1.24 | 7.38 × 10−5 | |
chr14.0021316565 | −1.29 | 2.23 × 10−2 | −1.56 | 2.05 × 10−4 | |
chr14.0025947530 | 0.91 | 1.48 × 10−2 | 1.05 | 7.13 × 10−3 | |
chr14.0080449863 | −1.84 | 5.11 × 10−5 | −1.74 | 2.05 × 10−4 | |
chr14.0085404000 | −1.38 | 4.50 × 10−3 | −1.38 | 3.07 × 10−3 | |
chr14.0104190006 | −1.48 | 3.71 × 10−3 | −1.75 | 2.66 × 10−4 | ZFYVE21 |
chr15.0046178808 | −0.97 | 1.71 × 10−2 | −0.70 | 4.78 × 10−2 | RP11—718O11.1 |
chr15.0069824154 | 1.42 | 1.25 × 10−4 | 1.55 | 4.82 × 10−6 | RP11—279F6.1 |
chr15.0092982723 | 1.45 | 3.91 × 10−5 | 1.73 | 9.39 × 10−9 | ST8SIA2 |
chr16.0004815786 | −0.89 | 8.94 × 10−4 | −0.92 | 9.24 × 10−3 | ZNF500 |
chr16.0077912976 | −1.23 | 8.49 × 10−3 | −1.28 | 2.22 × 10−3 | VAT1L |
chr16.0079468883 | 1.11 | 4.82 × 10−3 | 1.28 | 3.78 × 10−5 | |
chr17.0018941025 | −1.85 | 1.91 × 10−3 | −1.96 | 2.09 × 10−4 | GRAP |
chr17.0019045779 | −1.55 | 7.74 × 10−3 | −1.56 | 8.05 × 10−4 | GRAPL, CTC—457L16.2 |
chr17.0028803808 | −1.20 | 1.47 × 10−2 | −1.24 | 4.72 × 10−3 | |
chr17.0070499160 | 1.04 | 1.42 × 10−4 | 1.06 | 1.48 × 10−3 | LINC00511 |
chr17.0074566299 | 0.87 | 3.28 × 10−2 | 1.14 | 3.76 × 10−4 | ST6GALNAC2, RP11—666A8.9 |
chr18.0043923940 | −1.66 | 5.63 × 10−6 | −1.73 | 7.53 × 10−7 | RNF165 |
chr18.0045011716 | 1.10 | 2.73 × 10−2 | 1.41 | 4.57 × 10−5 | CTD—2130O13.1 |
chr18.0047177650 | −1.15 | 3.29 × 10−4 | −0.64 | 8.52 × 10−3 | |
chr18.0047230566 | −1.39 | 1.98 × 10−2 | −1.30 | 3.48 × 10−3 | |
chr18.0072250823 | 1.12 | 7.11 × 10−3 | 1.05 | 2.58 × 10−2 | CNDP1 |
chr19.0002867898 | 1.36 | 5.19 × 10−9 | 1.12 | 1.72 × 10−2 | ZNF556 |
chr19.0041126191 | −0.80 | 1.99 × 10−2 | −0.92 | 4.84 × 10−3 | LTBP4 |
chr20.0031210733 | 1.20 | 2.29 × 10−2 | 1.36 | 2.68 × 10−2 | |
chr20.0052825772 | −1.35 | 1.91 × 10−3 | −1.31 | 3.11 × 10−3 | PFDN4 |
chr20.0055369320 | −1.24 | 9.46 × 10−4 | −1.68 | 1.37 × 10−4 | |
chr20.0060501154 | 2.02 | 6.08 × 10−4 | 1.87 | 9.34 × 10−4 | CDH4 |
chr21.0030689317 | −0.78 | 4.49 × 10−3 | −0.86 | 1.16 × 10−3 | BACH1 |
chr22.0050332646 | −1.23 | 5.83 × 10−3 | −1.35 | 1.32 × 10−3 |
Chromosome | MB | MT | Muscle | Blood | ||||
---|---|---|---|---|---|---|---|---|
Significant CpGs | Enrichment p-Value | Significant CpGs | Enrichment p-Value | Significant CpGs | Enrichment p-Value | Significant CpGs | Enrichment p-Value | |
1 | 0 | 1.000 | 1 | 1.000 | 1 | 1.000 | 10 | 1.000 |
2 | 26 | 0.997 | 103 | 1.000 | 84 | 0.361 | 312 | 1.000 |
3 | 45 | 4.81 ×10−3 | 112 | 0.146 | 77 | 9.94 × 10−3 | 650 | 2.20 × 10−16 |
4 | 3 | 1.000 | 9 | 1.000 | 7 | 1.000 | 21 | 1.000 |
5 | 14 | 0.998 | 82 | 0.863 | 64 | 0.082 | 222 | 1.000 |
6 | 29 | 0.348 | 98 | 0.209 | 109 | 1.22 × 10−12 | 544 | 2.20 × 10−16 |
7 | 8 | 1.000 | 23 | 1.000 | 23 | 1.000 | 136 | 1.000 |
8 | 9 | 1.000 | 26 | 1.000 | 28 | 0.999 | 169 | 1.000 |
9 | 18 | 0.921 | 54 | 1.000 | 22 | 1.000 | 208 | 1.000 |
10 | 13 | 0.999 | 35 | 1.000 | 4 | 1.000 | 76 | 1.000 |
11 | 33 | 0.103 | 101 | 0.092 | 58 | 0.196 | 618 | 2.20 × 10−16 |
12 | 76 | 2.20 × 10−16 | 204 | 2.20 × 10−16 | 67 | 7.43 × 10−3 | 519 | 2.20 × 10−16 |
13 | 21 | 3.73 × 10−2 | 104 | 7.37 × 10−14 | 61 | 9.60 × 10−9 | 344 | 2.20 × 10−16 |
14 | 41 | 3.31 × 10−7 | 137 | 2.20 × 10−16 | 68 | 6.01 × 10−8 | 448 | 2.20 × 10−16 |
15 | 31 | 1.63 × 10−3 | 130 | 2.20 × 10−16 | 72 | 6.96 × 10−9 | 298 | 3.44 × 10−9 |
16 | 20 | 0.835 | 93 | 0.111 | 68 | 3.04 × 10−3 | 369 | 1.37 × 10−5 |
17 | 26 | 0.564 | 86 | 0.659 | 56 | 0.329 | 300 | 0.912 |
18 | 35 | 4.65 × 10−8 | 107 | 2.20 × 10−16 | 47 | 1.42 × 10−5 | 341 | 2.20 × 10−16 |
19 | 9 | 1.000 | 47 | 1.000 | 25 | 1.000 | 170 | 1.000 |
20 | 47 | 4.59 × 10−11 | 153 | 2.20 × 10−16 | 64 | 4.93 × 10−8 | 484 | 2.20 × 10−16 |
21 | 2 | 0.995 | 6 | 1.000 | 2 | 1.000 | 9 | 1.000 |
22 | 19 | 0.101 | 63 | 1.09 × 10−2 | 31 | 0.257 | 293 | 2.20 × 10−16 |
Total | 525 | 1774 | 1038 | 6541 |
TSS | LogFC | FDR Corrected p-Value | Gene | Class |
---|---|---|---|---|
chr16:51277965 | –0.85 | 3.82 × 10−4 | AC137527.2 | Pseudogene |
chr13:115039303 | 0.20 | 1.97 × 10−3 | MIR4502 | miRNA |
chr17:34397734 | 0.39 | 4.41 × 10−2 | CCL18 | Protein coding |
TSS | LogFC | FDR Corrected p-Value | Gene | Class |
---|---|---|---|---|
chr17:73070401 | 0.59 | 9.50 × 10−6 | AC111186.1 | Pseudogene |
chr17:75148756 | 0.36 | 4.01 × 10−4 | RNU4–47P | snRNA |
chr19:48673949 | 0.60 | 8.84 × 10−4 | ZSWIM9 | Protein coding |
chr11:46134769 | 0.55 | 1.51 × 10−3 | AC024475.1 | miRNA |
chr4:111866955 | 0.30 | 1.81 × 10−3 | LYPLA1P2 | Pseudogene |
chr12:7072409 | 0.25 | 6.45 × 10−3 | U47924.27 | lincRNA |
chr1:242187356 | –0.14 | 6.93 × 10−3 | RNU6–1139P | snRNA |
chr12:7072408 | 0.25 | 7.37 × 10−3 | EMG1 | Protein coding |
chr11:93971316 | 1.04 | 1.67 × 10−2 | RP11–680H20.2 | lincRNA |
chr2:47454056 | –0.67 | 4.96 × 10−2 | AC106869.2 | lincRNA |
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Robinson, K.G.; Marsh, A.G.; Lee, S.K.; Hicks, J.; Romero, B.; Batish, M.; Crowgey, E.L.; Shrader, M.W.; Akins, R.E. DNA Methylation Analysis Reveals Distinct Patterns in Satellite Cell–Derived Myogenic Progenitor Cells of Subjects with Spastic Cerebral Palsy. J. Pers. Med. 2022, 12, 1978. https://doi.org/10.3390/jpm12121978
Robinson KG, Marsh AG, Lee SK, Hicks J, Romero B, Batish M, Crowgey EL, Shrader MW, Akins RE. DNA Methylation Analysis Reveals Distinct Patterns in Satellite Cell–Derived Myogenic Progenitor Cells of Subjects with Spastic Cerebral Palsy. Journal of Personalized Medicine. 2022; 12(12):1978. https://doi.org/10.3390/jpm12121978
Chicago/Turabian StyleRobinson, Karyn G., Adam G. Marsh, Stephanie K. Lee, Jonathan Hicks, Brigette Romero, Mona Batish, Erin L. Crowgey, M. Wade Shrader, and Robert E. Akins. 2022. "DNA Methylation Analysis Reveals Distinct Patterns in Satellite Cell–Derived Myogenic Progenitor Cells of Subjects with Spastic Cerebral Palsy" Journal of Personalized Medicine 12, no. 12: 1978. https://doi.org/10.3390/jpm12121978