Genomic Analysis of Invasive Human Bone Marrow Derived Mesenchymal Stem Cells.
Genomic Analysis of Invasive Human Bone Marrow Derived Mesenchymal Stem Cells.
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DOI：
10.4172/2329-8820.1000122
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发表时间：
2013-05-23
期刊：
影响因子：
--
通讯作者：
Farrar WL
中科院分区：
文献类型：
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作者：
Mathews LA;Hurt EM;Zhang X;Farrar WL
人骨髓源性间充质干细胞（hMSC）能够分化成多种细胞谱系，并在各种治疗应用中显示出广泛的用途。直到最近，研究才开始了解hMSCs及其在体内和体外分化的对应物的基因表达谱。本研究旨在更好地了解hMSC通过基底膜侵入过程中存在的基因表达模式。使用Agilent的基因表达阵列和Matrigel侵袭室评估侵袭性和非侵袭性细胞之间的基因表达变化。这些细胞被特异性地吸引到一种称为SCM的干细胞培养基中。共有435个基因在侵袭性细胞群体中上调2倍或更多，并通过侵袭性途径分析（IPA）将其分类为发育程序和免疫/炎症信号传导途径。该列表包括多种生长和分化的调节剂，包括NANOG、STAT 3和STAT 5A以及多梳抑制复合物-2（PCRC 2）EZH 2和SUZ 12的成员。已知的炎症和缺氧调节因子HIF-1α也增加，表明微环境的调节在此过程中很重要。最后，可以使用STAT 3抑制剂Static逆转入侵过程。总的来说，这些数据将增加对hMSC侵袭过程中遗传途径功能的理解，并有助于其治疗应用的发展。
Human bone marrow derived mesenchymal stem cells (hMSCs) are capable of differentiation into multiple cell lineages and demonstrate a wide variety of use in various therapeutic applications. Only recently has research begun to understand the gene expression profiles of hMSCs and their differentiated counterparts in vivo and ex vivo. The research presented here aimed at gaining a better understanding of gene expression patterns present during hMSC invasion through a basement membrane. Changes in gene expression were evaluated between invasive and non-invasive cells using Agilent’s gene expression arrays and Matrigel invasion chambers. The cells were specifically attracted to a defined stem cell media called SCM. A total 435 genes were up-regulated by 2- fold or more in the invasive population of cells and classified into developmental programs and immunological/inflammatory signaling pathways determined by Ingenuity Pathway Analysis (IPA). This list included a variety of regulators of growth and differentiation including NANOG, STAT3 and STAT5A and members of the polycomb repressive complex-2 (PCRC2) EZH2 and SUZ12. The known regulator of inflammation and hypoxia HIF-1α was also increased suggesting that regulation of the microenvironment is important during this process. Finally, the invasion process could be reversed using the STAT3 inhibitor Static. Overall these data will increase the understanding of the genetic pathways functioning during hMSC invasion and aid in the development of their therapeutic applications.