Derynck Rik, Akhurst Rosemary J
Department of Cell and Tissue Biology, Program in Cell Biology, University of California - San Francisco, San Francisco, CA 94143-0512, USA.
Nat Cell Biol. 2007 Sep;9(9):1000-4. doi: 10.1038/ncb434.
During development, stem and progenitor cells gradually commit to differentiation pathways. Cell fate decisions are regulated by differentiation factors, which activate transcription programmes that specify lineage and differentiation status. Among these factors, the transforming growth factor (TGF)-beta family is important in both lineage selection and progression of differentiation of most, if not all, cell and tissue types. There is now increasing evidence that TGF-beta family proteins have the ability to redirect the differentiation of cells that either have fully differentiated or have engaged in differentiation along a particular lineage, and can thereby elicit 'transdifferentiation'. This capacity for cellular plasticity is critical for normal embryonic development, but when recapitulated in the adult it can give rise to, or contribute to, a variety of diseases. This is illustrated by the ability of TGF-beta family members to redirect epithelial cells into mesenchymal differentiation and to cause switching of mesenchymal cells from one lineage to another. Hence, various pathologies in adults may be considered diseases of abnormal development and differentiation.
在发育过程中，干细胞和祖细胞逐渐定向分化。细胞命运的决定受分化因子调控，这些因子激活特定谱系和分化状态的转录程序。在这些因子中，转化生长因子（TGF）-β家族对于大多数（即便不是全部）细胞和组织类型的谱系选择和分化进程都很重要。现在越来越多的证据表明，TGF-β家族蛋白能够使已经完全分化或已沿着特定谱系进行分化的细胞改变分化方向，从而引发“转分化”。这种细胞可塑性能力对于正常胚胎发育至关重要，但在成体中重现时，它会引发或促成多种疾病。TGF-β家族成员将上皮细胞重定向为间充质分化以及使间充质细胞从一个谱系转换为另一个谱系的能力就说明了这一点。因此，成人的各种病理状况可能被视为异常发育和分化的疾病。
