Boquest Andrew C, Noer Agate, Collas Philippe
Institute of Basic Medical Sciences, Department of Biochemistry, Faculty of Medicine, University of Oslo, Blindern, 0317 Oslo, Norway.
Stem Cell Rev. 2006;2(4):319-29. doi: 10.1007/BF02698059.
Stromal stem cells identified in various adult mesenchymal tissues (commonly called mesenchymal stem cells [MSCs]) have in past years received more attention as a result of their potential interest as replacement cells in regenerative medicine. An abundant and easily accessible source of adult human MSCs are stem cells harvested from liposuction material. Similarly to bone marrow-derived MSCs, human adipose tissue-derived stem cells (ASCs) can give rise to a variety of cell types in vitro and in vivo; however, they have a propensity to differentiate into primarily mesodermal lineages. Even so, their capacity to differentiate into nonadipogenic mesodermal pathways seems to be restricted. Emerging DNA methylation profiles at adipogenic and nonadipogenic gene promoters in freshly isolated, cultured, or differentiated ASCs aim to provide an epigenetic explanation for this restrictive differentiation potential. A review of these studies indicates that human ASCs are epigenetically marked by mosaic hypomethylation of adipogenic promoters, whereas nonadipogenic lineage-specific promoters are hypermethylated. Surprisingly, in vitro differentiation toward various pathways maintains the overall methylation profiles of undifferentiated cells, raising the hypothesis that ASCs are at least epigenetically preprogrammed for adipogenesis. Novel attempts at reprogramming the epigenome of MSCs have been initiated to enhance the differentiation capacity of these cells.
过去几年中，在各种成人间充质组织中发现的基质干细胞（通常称为间充质干细胞[MSCs]）因其在再生医学中作为替代细胞的潜在价值而受到更多关注。成人人类MSCs的一个丰富且易于获取的来源是从抽脂材料中收获的干细胞。与骨髓来源的MSCs类似，人类脂肪组织来源的干细胞（ASCs）在体外和体内都可以分化为多种细胞类型；然而，它们倾向于主要分化为中胚层谱系。即便如此，它们分化为非脂肪生成中胚层途径的能力似乎受到限制。新鲜分离、培养或分化的ASCs中脂肪生成和非脂肪生成基因启动子处新出现的DNA甲基化谱旨在为这种限制性分化潜能提供表观遗传学解释。对这些研究的综述表明，人类ASCs在表观遗传学上的特征是脂肪生成启动子的镶嵌式低甲基化，而非脂肪生成谱系特异性启动子则是高甲基化。令人惊讶的是，向各种途径的体外分化维持了未分化细胞的整体甲基化谱，这就提出了一个假设，即ASCs至少在表观遗传学上预先编程为脂肪生成。已经开始了重新编程MSCs表观基因组的新尝试，以增强这些细胞的分化能力。
