Global Transcriptomic Profiling of the Bone Marrow Stromal Microenvironment during Postnatal Development, Aging, and Inflammation
Summary: 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 ch...
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doaj-06f6986902894ccfb19a5144479fbecc2020-11-25T00:26:24ZengElsevierCell Reports2211-12472019-12-01291033133330.e4Global Transcriptomic Profiling of the Bone Marrow Stromal Microenvironment during Postnatal Development, Aging, and InflammationPatrick M. Helbling0Elena Piñeiro-Yáñez1Rahel Gerosa2Steffen Boettcher3Fátima Al-Shahrour4Markus G. Manz5César Nombela-Arrieta6Department of Medical Oncology and Hematology, University Hospital and University of Zurich, 8091 Zurich, SwitzerlandBioinformatics Unit, Spanish National Cancer Research Center (CNIO), 28029 Madrid, SpainDepartment of Medical Oncology and Hematology, University Hospital and University of Zurich, 8091 Zurich, SwitzerlandDepartment of Medical Oncology and Hematology, University Hospital and University of Zurich, 8091 Zurich, SwitzerlandBioinformatics Unit, Spanish National Cancer Research Center (CNIO), 28029 Madrid, SpainDepartment of Medical Oncology and Hematology, University Hospital and University of Zurich, 8091 Zurich, SwitzerlandDepartment of Medical Oncology and Hematology, University Hospital and University of Zurich, 8091 Zurich, Switzerland; Corresponding authorSummary: 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. : Using RNA sequencing, Helbling et al. analyze the dynamic changes in transcriptional landscape of four major bone marrow stromal cell types, from early postnatal to late aging stages and during responses to sterile infections. The authors reveal the activation of previously unappreciated global and cell-type-specific pro-inflammatory signatures during homeostatic aging. Keywords: stromal cells, bone marrow microenvironment, hematopoietic stem cells, niches, transcriptomics, aging, inflammationhttp://www.sciencedirect.com/science/article/pii/S2211124719314755 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Patrick M. Helbling Elena Piñeiro-Yáñez Rahel Gerosa Steffen Boettcher Fátima Al-Shahrour Markus G. Manz César Nombela-Arrieta |
spellingShingle |
Patrick M. Helbling Elena Piñeiro-Yáñez Rahel Gerosa Steffen Boettcher Fátima Al-Shahrour Markus G. Manz César Nombela-Arrieta Global Transcriptomic Profiling of the Bone Marrow Stromal Microenvironment during Postnatal Development, Aging, and Inflammation Cell Reports |
author_facet |
Patrick M. Helbling Elena Piñeiro-Yáñez Rahel Gerosa Steffen Boettcher Fátima Al-Shahrour Markus G. Manz César Nombela-Arrieta |
author_sort |
Patrick M. Helbling |
title |
Global Transcriptomic Profiling of the Bone Marrow Stromal Microenvironment during Postnatal Development, Aging, and Inflammation |
title_short |
Global Transcriptomic Profiling of the Bone Marrow Stromal Microenvironment during Postnatal Development, Aging, and Inflammation |
title_full |
Global Transcriptomic Profiling of the Bone Marrow Stromal Microenvironment during Postnatal Development, Aging, and Inflammation |
title_fullStr |
Global Transcriptomic Profiling of the Bone Marrow Stromal Microenvironment during Postnatal Development, Aging, and Inflammation |
title_full_unstemmed |
Global Transcriptomic Profiling of the Bone Marrow Stromal Microenvironment during Postnatal Development, Aging, and Inflammation |
title_sort |
global transcriptomic profiling of the bone marrow stromal microenvironment during postnatal development, aging, and inflammation |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2019-12-01 |
description |
Summary: 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. : Using RNA sequencing, Helbling et al. analyze the dynamic changes in transcriptional landscape of four major bone marrow stromal cell types, from early postnatal to late aging stages and during responses to sterile infections. The authors reveal the activation of previously unappreciated global and cell-type-specific pro-inflammatory signatures during homeostatic aging. Keywords: stromal cells, bone marrow microenvironment, hematopoietic stem cells, niches, transcriptomics, aging, inflammation |
url |
http://www.sciencedirect.com/science/article/pii/S2211124719314755 |
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