Hematology Division, Department of Oncology, Transplants and New Advances in Medicine, University of Pisa, Pisa, Italy.
PLoS One. 2010 Mar 25;5(3):e9861. doi: 10.1371/journal.pone.0009861.
We recently characterized a progenitor of mesodermal lineage (MPCs) from the human bone marrow of adults or umbilical cord blood. These cells are progenitors able to differentiate toward mesenchymal, endothelial and cardiomyogenic lineages. Here we present an extensive molecular characterization of MPCs, from bone marrow samples, including 39 genes involved in stem cell machinery, differentiation and cell cycle regulation.
METHODOLOGY/PRINCIPAL FINDINGS: MPCs are cytofluorimetrically characterized and quantitative RT-PCR was performed to evaluate the gene expression profile, comparing it with MSCs and hESCs lines. Immunofluorescence and dot-blot analysis confirm qRT-PCR data. MPCs exhibit an increased expression of OCT4, NANOG, SALL4, FBX15, SPP1 and to a lesser extent c-MYC and KLF4, but lack LIN28 and SOX2. MPCs highly express SOX15.
CONCLUSIONS/SIGNIFICANCE: MPCs express many pluripotency-associated genes and show a peculiar Oct-4 molecular circuit. Understanding this unique molecular mechanism could lead to identifying MPCs as feasible, long telomeres, target cells for reprogramming with no up-regulation of the p53 pathway. Furthermore MPCs are easily and inexpensively harvested from human bone marrow.
我们最近从成人骨髓或脐血中鉴定出一种中胚层祖细胞(MPC)。这些细胞是能够向间充质、内皮和心肌细胞谱系分化的祖细胞。在这里,我们对来自骨髓样本的 MPC 进行了广泛的分子特征分析,包括 39 个涉及干细胞机制、分化和细胞周期调控的基因。
方法/主要发现:我们通过细胞荧光分析对 MPC 进行了鉴定,并通过定量 RT-PCR 评估了基因表达谱,将其与间充质干细胞(MSCs)和人胚胎干细胞(hESCs)系进行了比较。免疫荧光和斑点印迹分析证实了 qRT-PCR 数据。MPC 表现出 OCT4、NANOG、SALL4、FBX15、SPP1 的表达增加,而 c-MYC 和 KLF4 的表达增加较少,但缺乏 LIN28 和 SOX2。MPC 高度表达 SOX15。
结论/意义:MPC 表达许多多能性相关基因,并显示出一种特殊的 Oct-4 分子回路。了解这种独特的分子机制可能有助于将 MPC 鉴定为可行的、端粒较长的、用于重编程的靶细胞,而不会上调 p53 途径。此外,MPC 可以从人类骨髓中轻易且经济地提取。