Department of Internal Medicine and Gastroenterology, Gemelli University Hospital, Catholic University of Sacred Heart, Rome, Italy.
Cytotherapy. 2011 Mar;13(3):329-40. doi: 10.3109/14653249.2010.515576. Epub 2010 Sep 20.
Bone marrow- and adipose tissue-derived mesenchymal stromal cells (MSC) represent promising sources for regenerative medicine. However, the precise molecular mechanisms underlying MSC stemness maintenance versus differentiation are not fully understood. The aim of this study was to compare the genome-wide expression profiles of bone marrow-and adipose tissue-derived MSC, in order to identify a common molecular stemness core.
Molecular profiling was carried out using Affymetrix microarray and relevant genes were further validated by Q-PCR.
We identified an overlapping dataset of 190 transcripts commonly regulated in both cell populations, which included several genes involved in stemness regulation (i.e. self-renewal potential and the ability to generate differentiated cells), various signaling pathways and transcription factors. In particular, we identified a central role of the Kruppel-like factor 4 (KLF4) DNA-binding protein in regulating MSC transcriptional activity.
Our results provide new insights toward understanding the molecular basis of MSC stemness maintenance and underline the ability of KLF4 to maintain cells in an undifferentiated state.
骨髓和脂肪组织来源的间充质基质细胞（MSC）是再生医学有前途的来源。然而，MSC 干性维持与分化的精确分子机制尚不完全清楚。本研究旨在比较骨髓和脂肪组织来源的 MSC 的全基因组表达谱，以鉴定一个共同的分子干性核心。
采用 Affymetrix 微阵列进行分子谱分析，并用 Q-PCR 进一步验证相关基因。
我们鉴定出两个细胞群体中共同调控的 190 个转录本的重叠数据集，其中包括几个参与干性调节的基因（即自我更新潜力和产生分化细胞的能力）、各种信号通路和转录因子。特别地，我们确定了 Kruppel 样因子 4（KLF4）DNA 结合蛋白在调节 MSC 转录活性中的核心作用。
我们的结果为理解 MSC 干性维持的分子基础提供了新的见解，并强调了 KLF4 维持细胞未分化状态的能力。
