# Single-Cell Multi-Omics Profiling of Human Septal Myectomy Tissue: Toward Precision Medicine in Obstructive Hypertrophic Cardiomyopathy

**Authors:** Quynh Nguyen, Jeremy Parker, Amrit Singh, Ying Wang, Jamil Bashir, Zachary Laksman

PMC · DOI: 10.3390/jpm16020088 · Journal of Personalized Medicine · 2026-02-04

## TL;DR

This paper reviews how single-cell and spatial multi-omics technologies are improving understanding of hypertrophic cardiomyopathy and paving the way for precision medicine.

## Contribution

The paper provides a synthesis of recent single-cell and spatial transcriptomic studies in HCM, highlighting their potential for precision medicine.

## Key findings

- Single-cell and spatial multi-omics reveal HCM as a complex, multicellular disease.
- These technologies identify cell-specific transcriptional programs and signaling pathways.
- Findings suggest new strategies for precision medicine in obstructive HCM.

## Abstract

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder most commonly caused by pathogenic variants in sarcomeric genes, yet many patients remain genotype-negative and the mechanisms linking genetic alterations to disease pathology are not fully understood. Traditional bulk analyses have provided limited insight into the cellular and molecular changes that drive disease progression. Recent advances in single-cell and spatial multi-omics technologies now allow detailed characterization of cell type-specific transcriptional programs, signaling pathways, and tissue remodeling within the human myocardium. These approaches have begun to redefine HCM as a complex, multicellular disease rather than a purely sarcomeric disorder. This review summarizes current single-cell and spatial transcriptomic studies of human septal myectomy tissue, outlines their major findings and limitations, and discusses how these data may inform the development of precision medicine strategies in obstructive HCM.

## Linked entities

- **Diseases:** hypertrophic cardiomyopathy (MONDO:0005045)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}, CSRP3 (cysteine and glycine rich protein 3) [NCBI Gene 8048] {aka CLP, CMD1M, CMH12, CRP3, MLP}, Creb5 (cAMP responsive element binding protein 5) [NCBI Gene 231991] {aka 9430076C15Rik, CRE-BPa, Crebpa, D430026C09Rik}, COL6A1 (collagen type VI alpha 1 chain) [NCBI Gene 1291] {aka BTHLM1, BTHLM1A, OPLL, UCHMD1, UCHMD1A}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, FHOD3 (formin homology 2 domain containing 3) [NCBI Gene 80206] {aka CMH28, FHOS2, Formactin2}, ETV1 (ETS variant transcription factor 1) [NCBI Gene 2115] {aka ER81}, XIRP2 (xin actin binding repeat containing 2) [NCBI Gene 129446] {aka CMYA3}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, COL1A1 (collagen type I alpha 1 chain) [NCBI Gene 1277] {aka CAFYD, EDSARTH1, EDSC, OI1, OI2, OI3}, Cox7b (cytochrome c oxidase subunit 7B) [NCBI Gene 66142] {aka 1110004F07Rik}, MEOX1 (mesenchyme homeobox 1) [NCBI Gene 4222] {aka KFS2, MOX1}, DCN (decorin) [NCBI Gene 1634] {aka CSCD, DSPG2, PG40, PGII, PGS2, SLRR1B}, ITGB1 (integrin subunit beta 1) [NCBI Gene 3688] {aka CD29, FNRB, GPIIA, MDF2, MSK12, VLA-BETA}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, COL3A1 (collagen type III alpha 1 chain) [NCBI Gene 1281] {aka EDS4A, EDSVASC, PMGEDSV}, Cox6c (cytochrome c oxidase subunit 6C) [NCBI Gene 12864], KLF5 (KLF transcription factor 5) [NCBI Gene 688] {aka BTEB2, CKLF, IKLF}, CD46 (CD46 molecule) [NCBI Gene 4179] {aka AHUS2, MCP, MIC10, TLX, TRA2.10}, DES (desmin) [NCBI Gene 1674] {aka CDCD3, CSM1, CSM2, LGMD1D, LGMD1E, LGMD2R}, Cox5b (cytochrome c oxidase subunit 5B) [NCBI Gene 12859], MYH7 (myosin heavy chain 7) [NCBI Gene 4625] {aka CMD1S, CMH1, CMYO7A, CMYO7B, CMYP7A, CMYP7B}, ACTC1 (actin alpha cardiac muscle 1) [NCBI Gene 70] {aka ACTC, ASD5, CMD1R, CMH11, LVNC4}, COL6A2 (collagen type VI alpha 2 chain) [NCBI Gene 1292] {aka BTHLM1, BTHLM1B, PP3610, UCMD1, UCMD1B}, Aebp1 (AE binding protein 1) [NCBI Gene 11568] {aka ACLP}, MYL3 (myosin light chain 3) [NCBI Gene 4634] {aka CMH8, MLC-lV/sb, MLC1SB, MLC1V, VLC1, VLCl}, CXCR6 (C-X-C motif chemokine receptor 6) [NCBI Gene 10663] {aka BONZO, CD186, CDw186, STRL33, TYMSTR}, MYL4 (myosin light chain 4) [NCBI Gene 4635] {aka ALC1, AMLC, GT1, PRO1957}, JPH2 (junctophilin 2) [NCBI Gene 57158] {aka CMD2E, CMH17, JP-2, JP2}, Runx1 (runt related transcription factor 1) [NCBI Gene 12394] {aka AML1, CBF-alpha-2, Cbfa2, Pebp2a2, Pebpa2b}, MYL2 (myosin light chain 2) [NCBI Gene 4633] {aka CMH10, MFM12, MLC-2, MLC-2s/v, MLC-2v, MLC2}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, TPM3 (tropomyosin 3) [NCBI Gene 7170] {aka CAPM1, CFTD, CMYO4A, CMYO4B, CMYP4A, CMYP4B}, CCN1 (cellular communication network factor 1) [NCBI Gene 3491] {aka CYR61, GIG1, IBP-10, IGFBP-10, IGFBP10}, TNNI2 (troponin I2, fast skeletal type) [NCBI Gene 7136] {aka AMCD2B, DA2B, DA2B1, FSSV, fsTnI}, MYBPC3 (myosin binding protein C3) [NCBI Gene 4607] {aka CMD1MM, CMH4, FHC, LVNC10, MYBP-C, cMyBP-C}, TNNT2 (troponin T2, cardiac type) [NCBI Gene 7139] {aka CMD1D, CMH2, CMPD2, LVNC6, RCM3, TnTC}, Nppa (natriuretic peptide type A) [NCBI Gene 230899] {aka ANP, Anf, CDD, Pnd}, Cd99 (CD99 antigen) [NCBI Gene 673094] {aka 1110061M03Rik, 2410026K10Rik, D4, Pilr-l, pilr-1}, NPPB (natriuretic peptide B) [NCBI Gene 4879] {aka BNP, Iso-ANP}, TPM1 (tropomyosin 1) [NCBI Gene 7168] {aka C15orf13, CMD1Y, CMH3, HEL-S-265, HTM-alpha, LVNC9}, Fgf12 (fibroblast growth factor 12) [NCBI Gene 14167] {aka B230343J05Rik, FGF-12, FHF-1, Fgf1a, Fhf1}, TRIM63 (tripartite motif containing 63) [NCBI Gene 84676] {aka CMH31, IRF, MURF1, MURF2, RNF28, SMRZ}, XIRP1 (xin actin binding repeat containing 1) [NCBI Gene 165904] {aka CMYA1, Xin}, LEF1 (lymphoid enhancer binding factor 1) [NCBI Gene 51176] {aka ECTD1, ECTD17, LEF-1, TCF10, TCF1ALPHA, TCF7L3}, TCF4 (transcription factor 4) [NCBI Gene 6925] {aka CDG2T, E2-2, FCD2, FECD3, ITF-2, ITF2}, CMYA5 (cardiomyopathy associated 5) [NCBI Gene 202333] {aka C5orf10, SPRYD2, TRIM76}, FAP (fibroblast activation protein alpha) [NCBI Gene 2191] {aka DPPIV, FAPA, FAPalpha, SIMP}, FLNC (filamin C) [NCBI Gene 2318] {aka ABP-280, ABP280A, ABPA, ABPL, ARVC15, CMD1PP}, Fn1 (fibronectin 1) [NCBI Gene 14268] {aka E330027I09, Fn, Fn-1}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, RTN4 (reticulon 4) [NCBI Gene 57142] {aka ASY, NI220/250, NOGO, NOGOA, NOGOB, NSP}, MYL7 (myosin light chain 7) [NCBI Gene 58498] {aka MYL2A, MYLC2A}, ACTA1 (actin alpha 1, skeletal muscle) [NCBI Gene 58] {aka ACTA, ASMA, CFTD, CFTD1, CFTDM, CMYO2A}, ZNF106 (zinc finger protein 106) [NCBI Gene 64397] {aka SH3BP3, ZFP106, ZNF474}, LUM (lumican) [NCBI Gene 4060] {aka LDC, SLRR2D}, CCN2 (cellular communication network factor 2) [NCBI Gene 1490] {aka CTGF, HCS24, IBP-8, IGFBP8, KMD, NOV2}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], COL1A2 (collagen type I alpha 2 chain) [NCBI Gene 1278] {aka EDSARTH2, EDSCV, OI4}
- **Diseases:** non-obstructive disease (MESH:D001157), left ventricular hypertrophy (MESH:D017379), contractile abnormality (MESH:D000014), atrial fibrillation (MESH:D001281), SARS-CoV-2 infection (MESH:D000086382), end-stage heart failure (MESH:D007676), cardiomyocyte hypertrophy (MESH:D006984), cardiovascular disease (MESH:D002318), inherited cardiac disorder (MESH:D006331), HCM (MESH:D002312), heart failure (MESH:D006333), ECG abnormalities (MESH:D053840), fibrosis (MESH:D005355), pressure overload (MESH:D019190), disease of (MESH:D004194), injury to (MESH:D014947), inflammation (MESH:D007249), sudden cardiac death (MESH:D016757), monogenic cardiomyopathies (MESH:D009202), arrhythmia (MESH:D001145), sarcomeric disorder (MESH:D009358), arrhythmic (OMIM:212500), obstructive (MESH:D000402)
- **Chemicals:** mavacamten (MESH:C000605992), Beta-adrenergic receptor blockers (-), steroid (MESH:D013256), ATP (MESH:D000255), calcium (MESH:D002118), dihydropyridine (MESH:C038806)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** Thr161Lys, p.(Cys150Tyr)

## Full text

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## References

65 references — full list in the complete paper: https://tomesphere.com/paper/PMC12942523/full.md

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Source: https://tomesphere.com/paper/PMC12942523