Abstract
BackgroundTissue regeneration and recovery in the adult body depends on self-renewal and differentiation of stem and progenitor cells. Mesenchymal stem cells (MSCs) that have the ability to differentiate into various cell types, have been isolated from the stromal fraction of virtually all tissues. However, little is known about the true identity of MSCs. MSC populations exhibit great tissue-, location- and patient-specific variation in gene expression and are heterogeneous in cell composition.Methodology/Principal FindingsOur aim was to analyze the dynamics of differentiation of two closely related stromal cell types, adipose tissue-derived MSCs (AdMSCs) and dermal fibroblasts (FBs) along adipogenic, osteogenic and chondrogenic lineages using multiplex RNA-seq technology. We found that undifferentiated donor-matched AdMSCs and FBs are distinct populations that stay different upon differentiation into adipocytes, osteoblasts and chondrocytes. The changes in lineage-specific gene expression occur early in differentiation and persist over time in both AdMSCs and FBs. Further, AdMSCs and FBs exhibit similar dynamics of adipogenic and osteogenic differentiation but different dynamics of chondrogenic differentiation.Conclusions/SignificanceOur findings suggest that stromal stem cells including AdMSCs and dermal FBs exploit different molecular mechanisms of differentiation to reach a common cell fate. The early mechanisms of differentiation are lineage-specific and are similar for adipogenic and osteogenic differentiation but are distinct for chondrogenic differentiation between AdMSCs and FBs.
Highlights
Tissue regeneration is dependent on progenitor cells that selfrenew and differentiate into different cell types with specialized functions
We have previously shown that dermal FBs and adipose tissuederived Mesenchymal stem cells (MSCs) (AdMSCs) originating from the same donors both differentiate into osteoblasts and adipocytes [14]
In vitro differentiation of AdMSCs and FBs was confirmed by detection of formation of lipid droplets with Oil Red O staining (ORO, adipocytes), matrix mineralization with Alizarin Red S staining (ARS, osteoblasts) or formation of proteoglycan-rich matrix with Alcian Blue staining (AB, chondrocytes)
Summary
Tissue regeneration is dependent on progenitor cells that selfrenew and differentiate into different cell types with specialized functions. Mesenchymal stem cells (MSCs) have been isolated from many different adult organs and tissues including skin, lung, liver and fat [1,2,3,4]. In vitro studies have demonstrated that MSCs can be expanded in culture and differentiated into several cell types under appropriate conditions. Differentiation of dermal fibroblasts (FBs) into various mesodermal cell types under similar conditions has produced contradictory results. Tissue regeneration and recovery in the adult body depends on self-renewal and differentiation of stem and progenitor cells. Mesenchymal stem cells (MSCs) that have the ability to differentiate into various cell types, have been isolated from the stromal fraction of virtually all tissues. MSC populations exhibit great tissue-, location- and patient-specific variation in gene expression and are heterogeneous in cell composition
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