Characterization of the bone marrow architecture of multiple myeloma using spatial transcriptomics
The bone marrow (BM) is a complex and compartmentalized tissue where spatial context plays a critical role in regulating cell behavior, signaling, and disease progression. To capture these dynamics, we apply spatial transcriptomics using the Visium Spatial Gene Expression platform on formalin-fixed paraffin-embedded (FFPE) BM sections from both healthy and Multiple Myeloma (MM) mouse models, as well as MM patient samples. Overcoming the technical challenges of working with mineralized long bone tissue, we develop a custom analytical framework integrating spatial and single-cell transcriptomic data to map cellular composition and interactions in situ. This approach enables the spatial characterization of transcriptionally heterogeneous malignant plasma cells (MM-PC) and their surrounding microenvironments. We identify spatially distinct gene programs linked to MM pathogenesis, including signatures of NETosis and IL-17 signalling, which are reduced in MM-PC-rich regions. Additionally, a transition gradient from effector to exhausted T cell phenotype is associated with increased remoteness from MM-PC. These spatial patterns are identified in FFPE BM biopsies from MM patients with varying tumor burdens. In summary, our study demonstrates both the capabilities and limitations of Visium technology in characterizing spatially regulated mechanisms underlying MM pathogenesis.
Authors
- Juan R. Rodríguez-Madoz (ORCID: https://orcid.org/0000-0003-4327-1866)
- Marta Abengózar (ORCID: https://orcid.org/0000-0003-3117-1884)
- José A. Martínez-Climent (ORCID: https://orcid.org/0000-0002-7938-3950)
- Marta Larráyoz (ORCID: https://orcid.org/0000-0001-6097-8244)
- Sarai Sarvide (ORCID: https://orcid.org/0000-0003-3528-9329)
- Felipe Prósper (ORCID: https://orcid.org/0000-0001-6115-8790)
- Vincenzo Lagani (ORCID: https://orcid.org/0000-0002-6552-6076)
- Emma Muiños Lopeź (ORCID: https://orcid.org/0000-0002-6618-4135)
- Miguel Cócera (ORCID: https://orcid.org/0000-0002-5679-1206)
- Luis Esteban Tamariz-Amador
- Purificación Ripalda‐Cemboráin (ORCID: https://orcid.org/0000-0001-8425-3563)
- Jesper Tegnér (ORCID: https://orcid.org/0000-0002-9568-5588)
- Laura Álvarez-Gigli (ORCID: https://orcid.org/0000-0002-7680-3569)
- Paula Aguirre‐Ruiz (ORCID: https://orcid.org/0000-0002-5871-372X)
- Patxi San Martín‐Úriz (ORCID: https://orcid.org/0000-0003-1483-4279)
- Itziar Cenzano (ORCID: https://orcid.org/0000-0002-9030-3069)
- Ana López-Pérez (ORCID: https://orcid.org/0000-0002-5159-0122)
- Phillip T. Newton (ORCID: https://orcid.org/0000-0003-2142-1798)
- David Gómez-Cabrero (ORCID: https://orcid.org/0000-0003-4186-3788)
- Ignacio Sancho (ORCID: https://orcid.org/0000-0002-1077-0354)
- Javier Ruiz (ORCID: https://orcid.org/0000-0001-6450-6375)
- Amaia Vilas‐Zornoza (ORCID: https://orcid.org/0000-0001-6693-0989)
- Borja Sáez (ORCID: https://orcid.org/0000-0001-7908-7089)
- Isabel A. Calvo (ORCID: https://orcid.org/0000-0001-6619-4571)
- Laura Sudupe
- Azari Bantan
- Aleksandra Kurowska (ORCID: https://orcid.org/0000-0001-5950-0358)
- Jin Ye (ORCID: https://orcid.org/0000-0002-7430-3915)
- Bruno Paiva
Institutions
- Karolinska University Hospital (SE)
- Ilia State University (GE)
- Science for Life Laboratory (SE)
- Karolinska Institutet (SE)
- Navarre Institute of Health Research (ES)
- Navarrabiomed (ES)
- Sachs' Children and Youth Hospital (SE)
- Clinica Universidad de Navarra (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- King Abdullah University of Science and Technology (SA)
- Universidad de Navarra (ES)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-11-20
- DOI
- https://doi.org/10.1038/s42003-025-08975-z
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Cancer Research UK
- European Commission
- Karolinska Institutet
- King Abdullah University of Science and Technology
- Universidad de Navarra
- Ministerio de Ciencia e Innovación
- Associazione Italiana per la Ricerca sul Cancro
- Universidad Pública de Navarra
- Science for Life Laboratory
- Centro de Investigación Biomédica en Red de Cáncer
- Gobierno de Navarra
- Horizon 2020 Framework Programme
- Instituto de Salud Carlos III
- European Regional Development Fund
- Division of Mathematical Sciences