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

• 作者: Betty Tan Bee Tee Candida Vaz Delicia Yong Qian Yi Lee Vivek Tanavde
• 来源期刊: 干细胞探索(英文)
• 学科: 医学
• 关键词: Mesenchymal Stromal CELLS (MSCs) Human Embryonic Stem CELLS DERIVED MSCS (hES-MSCs) FETAL LIMB DERIVED MSCS (Flb-MSCs) Bone Marrow DERIVED MSCS (BM-MSCs) Ontogenically DIFFERENT Sources Source Specific Canonical Pathways
• 年，卷（期）: 2017,（1）
• 页码范围: 1-26
• 页数: 26页
• 分类号: R73

摘要

Mesenchymal stromal cells (MSCs) can be obtained from several sources and the significant differences in their properties make 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 (5% - 16%) in differentially expressed gene sets 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 are 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.