Characterization of the bone marrow architecture of multiple myeloma using spatial transcriptomics
Year: 2025
Type: article
Abstract: 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.
Source: Communications Biology
Authors: Emma Muiños-Lopez, Ana Rosa Lopez-Perez, Laura Sudupe, Amaia Vilas-Zornoza, Sarai Sarvide, Purificacion Ripalda-Cemborain, Paula Aguirre-Ruiz, Patxi San Martin-Uriz, Marta Larrayoz, Laura Alvarez-Gigli, Marta Abengozar-Muela, Itziar Cenzano, Miguel Cócera, Javier Ruiz, Ignacio Sancho, Azari Bantan, Aleksandra Kurowska, Jin Ye, Phillip T. Newton, Bruno Paiva, Luis Esteban Tamariz-Amador, Juan R. Rodriguez-Madoz, Vincenzo Lagani, Jesper Tegner, Borja Saez, Jose Angel Martinez-Climent, Isabel A. Calvo, David Gomez-Cabrero, Felipe Prosper
Institutions: Navarre Institute of Health Research, Clinica Universidad de Navarra, Centro de Investigación Médica Aplicada, Universidad Pública de Navarra (UPNA), Navarrabiomed, King Abdullah University of Science and Technology, Centro de Investigación Biomédica en Red de Cáncer, Karolinska Institutet, Karolinska University Hospital, Ilia State University, Science for Life Laboratory
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,190
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
Awards: IDENTIFICACIÓN DE MECANISMOS TRANSCRIPCIONALES DE PROGRESIÓN Y RESISTENCIA AL TRATAMIENTO EN PACIENTES CON SINDROMES MIELODISPLASICOS DE ALTO RIESGO, G1727285392, G2415392674, G2559588348, G2628364946, Papel de los mecanismos de regulación trascripcional en la patogenia y el tratamiento de los SMD, G3024517585, G306212630, G3345895242, G3375147258, G3690828678, G36935394, G4937468798, G5175525644, G6052180468, G6329715174, Synapses between Leukaemia and its Neighbouring Cells, G7895849126, G8248449418, G8512683158, G8824911526
OpenAlex ID: W4416414562