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Global transcriptional profiling using RNA sequencing and DNA methylation patterns in highly enriched mesenchymal cells from young versus elderly women.

ABSTRACT: Purpose: Identification of relevant genetic pathways that are altered with aging knowing that the precursors for bone-forming osteoblasts reside in the mesenchymal cell population of bone marrow. Method: harvested and characterized, without in vitro culture, mesenchymal cells form human bone marrow capable of osteogenic differentiation Results: Identification of differentially regulated genes with aging in a highly enriched human bone marrow mesenchymal cell population. Conclusions: we have for the first time identified age-related differential gene expression and DNA methylation patterns in a highly enriched human bone marrow mesenchymal cell populationprofiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell or tissue. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE94736 | GEO | 2017/02/10

SECONDARY ACCESSION(S): PRJNA373887

REPOSITORIES: GEO

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Transcription profiling by array of human bone marrow hematopoietic stem cells from healthy young and elderly individuals

Project description:In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological disorders and malignancies. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. While the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have not yet been characterized. Gene expression profiling revealed that aged human HSC transcriptionally up-regulate genes associated with cell cycle, myeloid lineage specification, and myeloid malignancies. These age-associated alterations in the frequency, function, and gene expression profile of human HSC are significantly similar to those changes observed in mouse HSC, suggesting that hematopoietic aging is an evolutionarily conserved process. In order to elucidate the properties of an aged human hematopoietic system that may predispose to age-associated hematopoietic dysfunction, we evaluated HSC and other hematopoietic progenitor populations from healthy, hematologically normal young and elderly human bone marrow samples. We found that aged human HSC increase in frequency, are less quiescent, and exhibit myeloid-biased differentiation potential compared to young HSC.

2011-11-11 | E-GEOD-32719 | biostudies-arrayexpress

Altered granulopoiesis aggravates stroke in the elderly [bulk RNA-seq]

Project description:Ischemic stroke is one of the leading causes of disability and mortality worldwide, recognizing aging as a prominent risk factor and determinant of dismal outcome. Aging is known to lead to overall frailty due to multifactorial changes, but pathogenic mechanisms underlying poor outcome remain unclear. Here we show that deterioration in elderly stroke is preceded by neutrophil accumulation and clogging in the ischemic brain microcirculation leading to a worse no-reflow phenomenon. With high-dimensional single-cell profiling over time of the brain's, blood's, and bone marrow's immune response, we could delineate after stroke four main neutrophil clusters in the blood whose quantitative and temporal dynamic of release is deranged in the bone marrow of the old. In the elderly, stroke triggers an early surge in the blood of the CD62Llo neutrophil subset characterized by a signature of bone marrow proximity, senescence, and oxidative stress. Functionally, transfer of this neutrophil subset displaying prominent thrombogenic features in young stroke mice leads to increased clogging of the ischemic brain microcirculation, worse no-reflow and outcome. Interrogating the blood leukocyte landscape of a large human stroke cohort with extensive single-cell proteome analyses, we confirmed that older stroke patients display a similar precocious accumulation of blood CD62Llo neutrophil subset, worse reperfusion and outcome. Our results demonstrate how age-related alterations in the process of neutrophil differentiation and release from the bone marrow have a relevant pathogenic role in the major cerebrovascular disorder affecting the world population, that unleash emergency granulopoiesis.

2023-05-16 | GSE174438 | GEO

A mesenchymal stromal cell gene signature for donor age

Project description:Human aging is associated with loss of function and regenerative capacity. Human bone marrow derived mesenchymal stromal cells (hMSCs) are involved in tissue regeneration, evidenced by their capacity to differentiate into several lineages and therefore are considered the gold standard for cell-based regeneration therapy. Tissue maintenance and regeneration is dependent on stem cells and declines with age and aging is thought to influence therapeutic efficacy, therefore, more insight in the process of aging of hMSCs is of high interest. We, therefore, hypothesized that hMSCs might reflect signs of aging. In order to find markers for donor age, early passage hMSCs were isolated from bone marrow of 61 donors, with ages varying from 17-84, and clinical parameters, in vitro characteristics and microarray analysis were assessed. Although clinical parameters and in vitro performance did not yield reliable markers for aging since large donor variations were present, genome-wide microarray analysis resulted in a considerable list of genes correlating with human age. By comparing the transcriptional profile of aging in human with the one from rat, we discovered follistatin as a common marker for aging in both species. The gene signature presented here could be a useful tool for drug testing to rejuvenate hMSCs or for the selection of more potent, hMSCs for cell-based therapy. We used microaray gene expression profiling to find expressed genes that correlated with the donor age of bone-marrow derived mesenchymal stromal cells (hMSCs) Human mesenchymal stem cells (hMSC) were biopsied from bone marrow from 61 different donors aging from 17 - 89 years old. The genome wide expression profiles was assessed using Affymetrix microarrays. The expression of genes was correlated with the age of the donors.

2012-07-20 | E-GEOD-39540 | biostudies-arrayexpress

Single cell transcriptomics analysis of bone marrow mesenchymal lineage cells

Project description:Bone marrow mesenchymal lineage cells are a heterogeneous cell population involved in bone homeostasis and diseases such as osteoporosis. While it is long postulated that they originate from mesenchymal stem cells (MSCs), the true identity of MSCs and their in vivo bifurcated differentiation routes into osteoblasts and adipocytes remain poorly understood. Here, by employing large scale single cell transcriptome analysis, we computationally defined MSCs and delineated their bi-lineage differentiation paths in young, adult and aging mice. One identified subpopulation is a unique cell type that expresses adipocyte markers but contains no lipid droplets. As non-proliferative precursors for adipocytes, they exist abundantly as pericytes and stromal cells that form a ubiquitous 3D network inside the marrow cavity. Functionally they play critical roles in maintaining marrow vasculature and suppressing bone formation. Therefore, we name them marrow adipogenic lineage precursors (MALPs) and conclude that they are a new component of marrow adipose tissue.

2020-05-01 | GSE145477 | GEO

Extracellular vesicles from osteogenic differentiated human BMSCs

Project description:Pathological processes like osteoporosis or steroid-induced osteonecrosis of the hip are accompanied by increased bone marrow adipogenesis. Such disorder of adipogenic/osteogenic differentiation, which affects also bone marrow derived mesenchymal stem cells (BMSCs) contributes to bone loss during aging. Therefore, we investigated the effects of extracellular vesicles (EVs) isolated from human (h)BMSCs during different stages of osteogenic differentiation on osteogenic and adipogenic differentiation capacity of naïve hBMSCs.

2022-10-14 | PXD035845 | Pride

Transcriptomics of osteogenic and adipogenic progenitors

Project description:While the accumulation of bone marrow adipose tissue has been positively associated with aging and high fat diet, the physiological consequences are mostly unknown. It is well established that osteogenic and adipogenic progenitors share a common developmental origin.Unfavorable microenvironmental changes may bias these cell populations towards an adipogenic fate, which in turn could negatively influence bone homeostasis. Our previously collected data from mice reveal a high plasticity of the mesenchymal osteo-adipogenic stem cell population. Therefore, we now wish to perform by RNA-seq in defined cell population with varying adipogenic commitment within this heterogeneous stem cell pool.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

2016-04-11 | E-ERAD-460 | biostudies-arrayexpress

The gene expression profiles of human bone marrow stromal cells

Project description:Evidence suggests that the bone marrow microenvironment (niches) support hematopoietic stem cells (HSCs). The cell-cell interaction between bone marrow mesenchymal stromal cells (BMSCs) and HSCs plays a crucial role in hematopoiesis. The aging of BMSCs lead to decreased ability to maintain hematopoiesis. We used microarray to determine the age-related change of BMSCs.

2017-05-12 | GSE78235 | GEO

Human bone-derived 11Lin-CD45-CD271+SSEA-4+ mesenchymal stem/stromal cells from young and elderly patients

Project description:Global gene expressions of human bone-derived 11Lin-CD45-CD271+SSEA-4+ mesenchymal stem/stromal cells from young and elderly patients were analyzed. Results provide an insight into the molecular mechanisms of aging and cellular senescence.

2017-07-21 | GSE101694 | GEO

Investigating Global Changes in Gene Expression in a Murine Model of Cherubism

Project description:Purpose: To identify the mechanistic changes that lead to impaired osteogenesis and spontaneous osteoclast formation in both the hematopoietic and mesenchymal cell populations the makeup bone marrow cultures derived from cherubism mice (Sh3bp2KI/KI). Methods: Bone marrow cultures derived from wild type and cherubism mice were grown for seven days. On day seven, hematopoietic and mesenchymal cell types were sorted using CD45 and Sca1 cell surface markers. CD45+Sca1+ identified the hematopoietic population. CD45-Sca1+ identified the mesenchymal population. Total RNA was prepared from cell sorted populations. RNA quality was confirmed, ribosomal RNAs were depleted, libraries were prepared, and paired-end sequencing was performed on a illumina platform. We performed this study using six biological replicates. Results: Gene expression differences were identified Conclusions: Our study, for the first time, identifies the impact of a cherubism mutation on the global transcriptome of hematopoietic and mesenchymal cells extracted from murine bone marrow stromal cultures. With this study, we have found novel molecular signatures that are consistent with the cherubism phenotype (inflammation, bone loss, and fibrosis).

2019-10-26 | GSE139421 | GEO

Gene expression in bone marrow mesenchymal lineage cell and endothelial cell populations of Cxcr4WHIM/+ mice [BM]

Project description:This study provides gene expression profiles of bone marrow mesenchymal lineage cell and endothelial cell subsets from a CXCR4 gain-of- function mouse model of WHIM syndrome at the population level.

2021-12-04 | GSE189936 | GEO

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