Stem Cell–Related Gene Expression in Clonal Populations of Mesenchymal Stromal Cells from Bone Marrow

Abstract

Decline in the frequency of potent mesenchymal stem cells (MSCs) has been implicated in ageing and degenerative diseases. Increasing the circulating stem cell population can lead to renewed recruitment of these potent cells at sites of damage. Therefore, identifying the ideal cells for ex vivo expansion will form a major pursuit of clinical applications. This study is a follow-up of previous work that demonstrated the occurrence of fast-growing multipotential cells from the bone marrow samples. To investigate the molecular processes involved in the existence of such varying populations, gene expression studies were performed between fast- and slow-growing clonal populations to identify potential genetic markers associated with stemness using the quantitative real-time polymerase chain reaction comprising a series of 84 genes related to stem cell pathways. A group of 10 genes were commonly overrepresented in the fast-growing stem cell clones. These included genes that encode proteins involved in the maintenance of embryonic and neural stem cell renewal (sex-determining region Y-box 2, notch homolog 1, and delta-like 3), proteins associated with chondrogenesis (aggrecan and collagen 2 A1), growth factors (bone morphogenetic protein 2 and insulin-like growth factor 1), an endodermal organogenesis protein (forkhead box a2), and proteins associated with cell-fate specification (fibroblast growth factor 2 and cell division cycle 2). Expression of diverse differentiation genes in MSC clones suggests that these commonly expressed genes may confer the maintenance of multipotentiality and self-renewal of MSCs.

On the origin and impact of mesenchymal stem cell heterogeneity: new insights and emerging tools for single cell analysis

“…Certainly, there is great divergence in transcriptional signature between high-and lowpotential clones following exposure to differentiation conditions (Mareddy et al, 2010). There is also now evidence for clonal variation in basal gene expression in undifferentiated cells.…”

“…There is also now evidence for clonal variation in basal gene expression in undifferentiated cells. Screens comparing stem cell gene expression between fast-and slowgrowing clones identify extensive differences in the expression of genes associated with the cell cycle and cellular division (Mareddy et al, 2010;Menicanin et al, 2010). Fast-growing clones also express select growth factors (e.g.…”

The Key Regulatory Roles of the PI3K/Akt Signaling Pathway in the Functionalities of Mesenchymal Stem Cells and Applications in Tissue Regeneration

“…[1][2][3][4][5] A recent study showed that MSCs can be expanded for more than 50 passages in cell culure. 6 MSCs have a fibroblast-like morphology and express stromal markers, including CD73, CD105, CD29, CD44, and CD90, but not hematopoietic markers.…”

Metalloprotease-Disintegrin ADAM12 Expression Is Regulated by Notch Signaling via MicroRNA-29

“…Intriguingly, ADAM12 expression is also up-regulated in mesenchymal stem cells (11), neural stem cells (12), stem cells of the spleen (13), and stem cells of the liver (14). Each of these stem cell types is associated with high levels of Notch activity (13)(14)(15)(16)(17)(18). Furthermore, ADAM12 is expressed in regenerating skeletal muscle (19,20).…”