Vascular Biology Program, Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
J Cell Sci. 2012 Jul 1;125(Pt 13):3061-73. doi: 10.1242/jcs.093005. Epub 2012 Jul 13.
Transcriptional regulation contributes to the maintenance of pluripotency, self-renewal and differentiation in embryonic cells and in stem cells. Therefore, control of gene expression at the level of transcription is crucial for embryonic development, as well as for organogenesis, functional adaptation, and regeneration in adult tissues and organs. In the past, most work has focused on how transcriptional regulation results from the complex interplay between chemical cues, adhesion signals, transcription factors and their co-regulators during development. However, chemical signaling alone is not sufficient to explain how three-dimensional (3D) tissues and organs are constructed and maintained through the spatiotemporal control of transcriptional activities. Accumulated evidence indicates that mechanical cues, which include physical forces (e.g. tension, compression or shear stress), alterations in extracellular matrix (ECM) mechanics and changes in cell shape, are transmitted to the nucleus directly or indirectly to orchestrate transcriptional activities that are crucial for embryogenesis and organogenesis. In this Commentary, we review how the mechanical control of gene transcription contributes to the maintenance of pluripotency, determination of cell fate, pattern formation and organogenesis, as well as how it is involved in the control of cell and tissue function throughout embryogenesis and adult life. A deeper understanding of these mechanosensitive transcriptional control mechanisms should lead to new approaches to tissue engineering and regenerative medicine.
转录调控有助于胚胎细胞和干细胞中多能性、自我更新和分化的维持。因此，转录水平的基因表达控制对于胚胎发育以及成年组织和器官的器官发生、功能适应和再生至关重要。过去，大多数工作都集中在转录调控如何通过发育过程中化学信号、黏附信号、转录因子及其共调节剂之间的复杂相互作用产生。然而，仅化学信号不足以解释三维（3D）组织和器官如何通过转录活性的时空控制来构建和维持。越来越多的证据表明，机械线索包括物理力（例如张力、压缩或切应力）、细胞外基质（ECM）力学的改变以及细胞形状的变化，直接或间接地传递到细胞核，以协调对胚胎发生和器官发生至关重要的转录活性。在这篇评论中，我们回顾了基因转录的机械控制如何有助于多能性的维持、细胞命运的决定、模式形成和器官发生，以及它如何参与整个胚胎发生和成年生活过程中对细胞和组织功能的控制。对这些机械敏感的转录控制机制的更深入了解，应该会为组织工程和再生医学带来新的方法。
