Belema Bedada Fikru, Technau Antje, Ebelt Henning, Schulze Manja, Braun Thomas
Max Planck Institute for Heart and Lung Research, Parkstrasse 1, 61231 Bad Nauheim, Germany.
Mol Cell Biol. 2005 Nov;25(21):9509-19. doi: 10.1128/MCB.25.21.9509-9519.2005.
During embryogenesis, various cell types can be programmed by potent inducers to follow distinct differentiation paths. In adult life, this ability seems to be restricted to specific multipotent cells. We have identified two cell populations from adult murine bone marrow which express various "stemness" genes. Treatment with Wnt molecules induced transcription of different skeletal muscle marker genes and evoked expression of cardiomyocyte markers. Further characterization of Wnt-induced intracellular signaling cascades revealed that the skeletal muscle program depended on canonical Wnt signaling, while the induction of cardiomyocyte markers seems to require a protein kinase C-dependent pathway. CDO, another component of the machinery directing skeletal muscle induction and expansion, selectively activated skeletal muscle- but not cardiomyocyte-specific genes. Although we were able to turn on various cell-type-specific markers by different induction regimens, we never obtained fully differentiated, functional cells. We conclude that the differentiation of adult stem cells is incomplete and lacks certain cues necessary to acquire a truly functional status.
在胚胎发生过程中，各种细胞类型可被强效诱导剂编程，以遵循不同的分化路径。在成年期，这种能力似乎仅限于特定的多能细胞。我们从成年小鼠骨髓中鉴定出了两个表达多种“干性”基因的细胞群体。用Wnt分子处理可诱导不同骨骼肌标记基因的转录，并引发心肌细胞标记物的表达。对Wnt诱导的细胞内信号级联的进一步表征表明，骨骼肌程序依赖于经典Wnt信号传导，而心肌细胞标记物的诱导似乎需要蛋白激酶C依赖性途径。CDO是指导骨骼肌诱导和扩张机制的另一个组成部分，它选择性地激活骨骼肌特异性基因，而非心肌细胞特异性基因。尽管我们能够通过不同的诱导方案开启各种细胞类型特异性标记物，但我们从未获得完全分化的功能性细胞。我们得出结论，成体干细胞的分化是不完全的，并且缺乏获得真正功能状态所需的某些线索。
