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Epigenetic and in vivo comparison of diverse mesenchymal stromal cell sources reveals an endochonrdal signature for human hematopoietic niche formation

ABSTRACT: Despite similarities in morphology, phenotype and in vitro behavior, Mesenchymal Stromal Cells (MSC) form various tissue sources show striking differences in their in vivo potential to form bone, cartilage and hematopoietic support tissue. Comparing four commonly use MSC sources (bone marrow (BM), white adipose tissue (WAT), umbilical cord (UC) and skin) we found only bone marrow (BM)-derived MSCs capable of endochondral ossification and marrow attraction. To gain mechanistic insights explaining this differences we analyzed gene expression characteristics of MSC from all four tissue sources using Affymetrix Genechip Human Gene 2.0 ST Array.

ORGANISM(S): Homo sapiens

PROVIDER: GSE57151 | GEO | 2014/04/30

SECONDARY ACCESSION(S): PRJNA245789

REPOSITORIES: GEO

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Epigenetic and in vivo comparison of diverse mesenchymal stromal cell sources reveals an endochonrdal signature for human hematopoietic niche formation

Project description:Despite similarities in morphology, phenotype and in vitro behavior, Mesenchymal Stromal Cells (MSC) form various tissue sources show striking differences in their in vivo potential to form bone, cartilage and hematopoietic support tissue. Comparing four commonly use MSC sources (bone marrow (BM), white adipose tissue (WAT), umbilical cord (UC) and skin) we found only bone marrow (BM)-derived MSCs capable of endochondral ossification and marrow attraction. To gain mechanistic insights explaining this differences we analyzed gene expression characteristics of MSC from all four tissue sources using Affymetrix Genechip Human Gene 2.0 ST Array. MSCs from BM, WAT, UC and skin were isolated using plastic adherence. Cells were expanded in standard alpha-MEM supplemented with pooled human platelet lysate fully replacing fetal bovine serum. MSCs were subcutaneously implanted into immune-compromised mice to comparatively evaluate bone formation and subsequent bone marrow attraction. In parallel we have isolated RNA from all sources to analyze tissue source specific gene expression profile.

2014-04-30 | E-GEOD-57151 | biostudies-arrayexpress

Human bone and marrow niche formation by mesenchymal progenitors in vivo is predefined by an organotypic epigenetic signature

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Single-cell RNA sequencing of mesenchymal stromal cells from primary donor-matched tissue sources reveals functional heterogeneity in immune activity and cell motility

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Mesenchymal Stromal Cells Derived from Human Embryonic Stem Cells, Fetal Limb and Bone Marrow Share a Common Phenotype but are Transcriptionally and Biologically Different [II]

Project description:Mesenchymal stromal cells (MSCs) can be obtained from several sources and the significant differences in their properties, makes it crucial to investigate the differentiation potential of MSCs from different sources to determine the optimal source of MSCs. We investigated if this biological heterogeneity in MSCs from different sources results in different mechanisms for their differentiation. In this study, we compared the gene expression patterns of phenotypically defined MSCs derived from three ontogenically different sources: Embryonic stem cells (hES-MSCs), Fetal limb (Flb-MSCs) and Bone Marrow (BM-MSCs). Differentially expressed genes between differentiated cells and undifferentiated controls were compared across the three MSC sources. We found minimal overlap in differential gene expression (5-16%) among the three sources. Flb-MSCs were similar to BM-MSCs based on differential gene expression patterns. Pathway analysis of the differentially expressed genes using Ingenuity Pathway Analysis (IPA) revealed a large variation in the canonical pathways leading to MSC differentiation. The similar canonical pathways among the three sources were lineage specific. The Flb-MSCs showed maximum overlap of canonical pathways with the BM-MSCs, indicating that the Flb-MSCs is an intermediate source between the less specialised hES-MSC source and the more specialised BM-MSC source. The source specific pathways prove that MSCs from the three ontogenically different sources use different biological pathways to obtain similar differentiation outcomes. Thus our study advocates the understanding of biological pathways to obtain optimal sources of MSCs for various clinical applications.

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