Single-cell transcriptional profiling reveals a novel RAB13+ endothelial subpopulation and profibrotic mesenchymal cells in the aged human bone marrow

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

ABSTRACT The bone marrow (BM) microenvironment plays a crucial role in regulating hematopoiesis, yet the molecular and functional changes associated with aging humans remain poorly understood. Using single-cell RNA sequencing (scRNA-seq), we uncovered transcriptional shifts BM endothelial cells (EC) mesenchymal stem (MSC) during aging. Our analysis revealed that aged sinusoidal EC adopt prothrombotic, exhibit mitochondrial dysfunction, have compromised vascular function. Additionally, identified unique arterial subset, present only individuals, elongation senescence processes characterized by RAB13 expression. MSC from subjects displayed an impaired matrix remodeling epithelial-mesenchymal transition, driven partly subpopulation of THY1 + profibrotic stromal absent young subjects. Aged were also increased ATP-oxidative metabolism reduced protein folding capacity. Finally, using immunofluorescent imaging spatial transcriptomics, confirmed presence senescent samples significant age-related cell-cell communication within niche. In summary, this work provides comprehensive view diversity, cellular interactions, organization MSC, offering novel insights potential targets could be exploited for preventing aged-associated humans.

Language: Английский

Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 26, 2025

Abstract Multiple myeloma (MM) is a hematological malignancy defined by the abnormal proliferation and accumulation of plasma cells (PC) within bone marrow (BM). While multiple impacts bone, it not classified as primary cancer. The microenvironment significantly influences progression its treatment response. Mesenchymal stromal (MSCs) in this environment engage with other components via direct contact secretion soluble factors. This review examines established roles MSCs facets MM pathology, encompassing their pro-inflammatory functions, contributions to tumor epigenetics, effects on immune checkpoint inhibitors (ICIs), influence reprogramming, chemotherapy resistance, senescence. investigates role development MM.

Language: Английский