Stem Cell & Leukemia Laboratory, Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.
Translational Research Unit of Excellence (TRUE), Kolkata, India.
FASEB J. 2021 Jan;35(1):e21234. doi: 10.1096/fj.202002232R.
Emerging evidences highlight importance of epigenetic regulation and their integration with transcriptional and cell signaling machinery in determining tissue resident adult pluripotent mesenchymal stem/stromal cell (MSC) activity, lineage commitment, and multicellular development. Histone modifying enzymes and large multi-subunit chromatin remodeling complexes and their cell type-specific plasticity remain the central defining features of gene regulation and establishment of tissue identity. Modulation of transcription factor expression gradient ex vivo and concomitant flexibility of higher order chromatin architecture in response to signaling cues are exciting approaches to regulate MSC activity and tissue rejuvenation. Being an important constituent of the adult bone marrow microenvironment/niche, pathophysiological perturbation in MSC homeostasis also causes impaired hematopoietic stem/progenitor cell function in a non-cell autonomous mechanism. In addition, pluripotent MSCs can function as immune regulatory cells, and they reside at the crossroad of innate and adaptive immune response pathways. Research in the past few years suggest that MSCs/stromal fibroblasts significantly contribute to the establishment of immunosuppressive microenvironment in shaping antitumor immunity. Therefore, it is important to understand mesenchymal stromal epigenome and transcriptional regulation to leverage its applications in regenerative medicine, epigenetic memory-guided trained immunity, immune-metabolic rewiring, and precision immune reprogramming. In this review, we highlight the latest developments and prospects in chromatin biology in determining MSC function in the context of lineage commitment and immunomodulation.
新兴证据强调了表观遗传调控的重要性，以及它们与转录和细胞信号机制的整合，以决定组织驻留的成体多能间充质干细胞/基质细胞 (MSC) 的活性、谱系决定和多细胞发育。组蛋白修饰酶和大型多亚基染色质重塑复合物及其细胞类型特异性可塑性仍然是基因调控和组织身份建立的核心特征。体外调节转录因子表达梯度，以及对信号的高级染色质结构的伴随灵活性，是调节 MSC 活性和组织再生的令人兴奋的方法。作为成人骨髓微环境/生态位的重要组成部分，MSC 稳态的病理生理扰动也以非细胞自主机制导致造血干细胞/祖细胞功能受损。此外，多能 MSCs 可以作为免疫调节细胞发挥作用，它们位于先天和适应性免疫反应途径的交汇处。过去几年的研究表明，MSCs/基质成纤维细胞在塑造抗肿瘤免疫方面显著有助于建立免疫抑制微环境。因此，了解间充质基质的表观基因组和转录调控，以利用其在再生医学、表观遗传记忆指导的训练性免疫、免疫代谢重编程和精确免疫重编程中的应用非常重要。在这篇综述中，我们强调了染色质生物学在决定 MSC 在线粒体决定和免疫调节方面的功能的最新进展和前景。
