In situ spatial transcriptomic analysis of human skeletal muscle using the Xenium platform

Umek, Nejc (avtor), Meznarič, Marija (avtor), Šink, Žiga (avtor), Blagotinšek Cokan, Kaja (avtor), Prosenc Zmrzljak, Uršula (avtor), Horvat, Simon (avtor)

Traditional transcriptomic studies often overlook the complex heterogeneity of skeletal muscle, as they typically isolate RNA from mixed muscle fibre and cell populations, resulting in an averaged transcriptomic profile that obscures fibre type-specific differences. This study assessed the potential of the recently developed Xenium platform for high-resolution spatial transcriptomic analysis of human skeletal muscle histological sections. Human vastus lateralis muscle samples from two individuals were analysed using the Xenium platform and Human Multi-Tissue and Cancer Panel targeting 377 genes complemented by staining of successive sections for Myosin Heavy Chain isoforms to differentiate between type 1 and type 2 muscle fibres. Manual segmentation of muscle fibres allowed accurate comparisons of transcript densities across fibre types and subcellular regions, overcoming limitations in the platform’s automated segmentation. The analysis revealed higher transcript density in type 1 fibres, particularly in nuclear and perinuclear areas, and identified 191 out of 377 genes with differential expression between muscle fibres and perimysium. Genes such as PROX1, S100A1, LGR5, ACTA2, and LPL exhibited higher expression in type 1 fibres, whereas PEBP4, CAVIN1, GATM, and PVALB in type 2 fibres. We demonstrated that the Xenium platform is capable of high-resolution spatial in situ transcriptomic analysis of skeletal muscle histological sections. This study demonstrates that, with manual segmentation, the Xenium platform effectively performs fibre type-specific transcriptomic analysis, providing new insights into skeletal muscle biology.

• Jezik: Angleški jezik
• Ključne besede: spatial transcriptomic, skeletal muscle, xenium platform, muscle fibre, segmentation
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta ; BF - Biotehniška fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2025
• Št. strani: Str. 291-302
• Številčenje: Vol. 399, iss. 3
• PID: 20.500.12556/RUL-168472
• UDK: 575
• ISSN pri članku: 0302-766X
• DOI: 10.1007/s00441-024-03945-z
• COBISS.SI-ID: 221773059
• Datum objave v RUL: 15.04.2025

Gradivo je del revije

• Naslov: Cell and tissue research
• Skrajšan naslov: Cell Tissue Res
• Založnik: Springer New York, Springer
• ISSN: 0302-766X
• COBISS.SI-ID: 17175

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: genetika, skeletne mišice, transkriptomika

Projekti

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P3-0043
• Naslov: Molekularni mehanizmi razvoja in delovanja skeletne mišice

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P4-0220
• Naslov: Primerjalna genomika in genomska biodiverziteta