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Cell Rep. 2019 Dec 3;29(10):3313-3330.e4. doi: 10.1016/j.celrep.2019.11.004.

Global Transcriptomic Profiling of the Bone Marrow Stromal Microenvironment during Postnatal Development, Aging, and Inflammation.

Author information

1
Department of Medical Oncology and Hematology, University Hospital and University of Zurich, 8091 Zurich, Switzerland.
2
Bioinformatics Unit, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain.
3
Department of Medical Oncology and Hematology, University Hospital and University of Zurich, 8091 Zurich, Switzerland. Electronic address: Cesar.NombelaArrieta@usz.ch.

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.

KEYWORDS:

aging; bone marrow microenvironment; hematopoietic stem cells; inflammation; niches; stromal cells; transcriptomics

PMID:
31801092
DOI:
10.1016/j.celrep.2019.11.004
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