Global transcriptomic profiling of the bone marrow stromal microenvironment during postnatal development, aging, and inflammation
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Abstract
Bone marrow (BM) stromal cells provide the regulatory framework for hematopoiesis and contribute to developmental stage-specific niches, such as those preserving hematopoietic stem cells. Despite advances in our understanding of stromal function, little is known about the transcriptional changes that this compartment undergoes throughout lifespan and during adaptation to stress. Using RNA sequencing, we perform transcriptional analyses of four principal stromal subsets, namely CXCL12-abundant reticular, platelet-derived growth factor receptor (PDGFR)-α + Sca1 + , sinusoidal, and arterial endothelial cells, from early postnatal, adult, and aged mice. Our data reveal (1) molecular fingerprints defining cell-specific anatomical and functional features, (2) a radical reprogramming of pro-hematopoietic, immune, and matrisomic transcriptional programs during the transition from juvenile stages to adulthood, and (3) the aging-driven progressive upregulation of pro-inflammatory gene expression in stroma. We further demonstrate that transcriptomic pathways elicited in vivo by prototypic microbial molecules are largely recapitulated during aging, thereby supporting the inflammatory basis of age-related adaptations of BM hematopoietic function.
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Increased IL-1 BM level is a hallmark of hematopoietic inflammaging in mice.
“Increased IL-1 BM level, produced by different cellular sources, is a hallmark of hematopoietic inflammaging in mice.21,22,42”
From Aging drives <i>Tet2</i> <i>+/−</i> clonal hematopoiesis via IL-1 signaling (2023) · cites this paper as [42]
The ‘Increased Pro-inflammatory Signatures in Aged BM Stroma’ section reports increased Il1b expression in bone marrow stromal cells of aged mice and an enhanced inflammatory milieu. It does not establish increased IL-1 protein levels throughout the bone marrow or show production by different cellular sources. (LLM, conf=0.86)
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- Authors
- Helbling, P. M., Piñeiro-Yáñez, E., Gerosa, R., Boettcher, S., Al-Shahrour, F., Manz, M. G., & Nombela-Arrieta, C.
- Affiliations
- University of Zurich (CH)
- Spanish National Cancer Research Centre (ES)
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 29
- Issue
- 10
- Pages
- 3313-3330.e4
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2992924016
- Cited by
- 116
- References
- 10
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 19 · 2023: 15 · 2022: 21 · 2021: 23 · 2020: 11 · 2019: 1
- FWCI
- 9.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- European Regional Development Fund (RETOS RTI2018-097596-B-I00)
- European Commission
- University of the East
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030B_166673/1, 31003A_159597/1)
- Helmut Horten Stiftung
- Krebsliga Schweiz
- Instituto de Salud Carlos III
- Universität Zürich
- Marie Curie (PCIG13-GA-2013-618633)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- bone marrow stroma, gene expression profiling, postnatal development, aging, inflammation, hematopoiesis, endothelial cells, sinusoidal endothelium, arterial endothelium, pro-inflammatory gene expression, hematopoietic function, stromal reprogramming
- MeSH terms
- Aging, Animals, Bone Marrow, Bone Marrow Cells, Cell Differentiation, Cells, Cultured, Hematopoiesis, Hematopoietic Stem Cells, Inflammation, Male, Mice, Inbred C57BL, Gene Expression Profiling, Endothelial Cells, Embryonic Development, Mice, Chemokine CXCL12, Stem Cell Niche, Transcriptome, Mesenchymal Stem Cells, Cellular Microenvironment
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