Ulloa-Montoya Fernando, Kidder Benjamin L, Pauwelyn Karen A, Chase Lucas G, Luttun Aernout, Crabbe Annelies, Geraerts Martine, Sharov Alexei A, Piao Yulan, Ko Minoru S H, Hu Wei-Shou, Verfaillie Catherine M
Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA.
Genome Biol. 2007;8(8):R163. doi: 10.1186/gb-2007-8-8-r163.
Recently, several populations of postnatal stem cells, such as multipotent adult progenitor cells (MAPCs), have been described that have broader differentiation ability than classical adult stem cells. Here we compare the transcriptome of pluripotent embryonic stem cells (ESCs), MAPCs, and lineage-restricted mesenchymal stem cells (MSCs) to determine their relationship.
Applying principal component analysis, non-negative matrix factorization and k-means clustering algorithms to the gene-expression data, we identified a unique gene-expression profile for MAPCs. Apart from the ESC-specific transcription factor Oct4 and other ESC transcripts, some of them associated with maintaining ESC pluripotency, MAPCs also express transcripts characteristic of early endoderm and mesoderm. MAPCs do not, however, express Nanog or Sox2, two other key transcription factors involved in maintaining ESC properties. This unique molecular signature was seen irrespective of the microarray platform used and was very similar for both mouse and rat MAPCs. As MSC-like cells isolated under MAPC conditions are virtually identical to MSCs, and MSCs cultured in MAPC conditions do not upregulate MAPC-expressed transcripts, the MAPC signature is cell-type specific and not merely the result of differing culture conditions.
Multivariate analysis techniques clustered stem cells on the basis of their expressed gene profile, and the genes determining this clustering reflected the stem cells' differentiation potential in vitro. This comparative transcriptome analysis should significantly aid the isolation and culture of MAPCs and MAPC-like cells, and form the basis for studies to gain insights into genes that confer on these cells their greater developmental potency.
最近，已描述了几种产后干细胞群体，如多能成体祖细胞（MAPC），它们具有比经典成体干细胞更广泛的分化能力。在这里，我们比较多能胚胎干细胞（ESC）、MAPC和谱系受限间充质干细胞（MSC）的转录组，以确定它们之间的关系。
将主成分分析、非负矩阵分解和k均值聚类算法应用于基因表达数据，我们确定了MAPC独特的基因表达谱。除了ESC特异性转录因子Oct4和其他一些与维持ESC多能性相关的ESC转录本外，MAPC还表达早期内胚层和中胚层特征性的转录本。然而，MAPC不表达Nanog或Sox2，这是另外两个参与维持ESC特性的关键转录因子。无论使用何种微阵列平台，这种独特的分子特征都能被观察到，并且小鼠和大鼠的MAPC非常相似。由于在MAPC条件下分离的MSC样细胞与MSC几乎相同，并且在MAPC条件下培养的MSC不会上调MAPC表达的转录本，因此MAPC特征是细胞类型特异性的，而不仅仅是不同培养条件的结果。
多变量分析技术根据干细胞的表达基因谱对其进行聚类，决定这种聚类的基因反映了干细胞在体外的分化潜能。这种比较转录组分析应能显著有助于MAPC和MAPC样细胞的分离和培养，并为深入了解赋予这些细胞更强发育潜能的基因的研究奠定基础。
