State Key Laboratory of Component-Based Chinese Medicine, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong SAR, China.
Cell Death Dis. 2022 Oct 18;13(10):880. doi: 10.1038/s41419-022-05325-3.
SH3 and multiple ankyrin repeat domains protein (SHANK) 1, SHANK2, and SHANK3 encode a family of postsynaptic scaffolding proteins present at glutamatergic synapses and play a crucial role in synaptogenesis. In the past years, studies have provided a preliminary appreciation and understanding of the influence of the SHANK family in controlling stem cell fate. Here, we review the modulation of SHANK gene expression and their related signaling pathways, allowing for an in-depth understanding of the role of SHANK in stem cells. Besides, their role in governing stem cell self-renewal, proliferation, differentiation, apoptosis, and metabolism are explored in neural stem cells (NSCs), stem cells from apical papilla (SCAPs), and induced pluripotent stem cells (iPSCs). Moreover, iPSCs and embryonic stem cells (ESCs) have been utilized as model systems for analyzing their functions in terms of neuronal development. SHANK-mediated stem cell fate determination is an intricate and multifactorial process. This study aims to achieve a better understanding of the role of SHANK in these processes and their clinical applications, thereby advancing the field of stem cell therapy. This review unravels the regulatory role of the SHANK family in the fate of stem cells.
SH3 和多重复合结构域蛋白（SHANK）1、SHANK2 和 SHANK3 编码一组存在于谷氨酸能突触的突触后支架蛋白家族，在突触发生中发挥关键作用。在过去的几年中，研究初步认识和理解了 SHANK 家族在控制干细胞命运方面的影响。在这里，我们综述了 SHANK 基因表达的调控及其相关信号通路，以便深入了解 SHANK 在干细胞中的作用。此外，还探讨了 SHANK 在神经干细胞（NSCs）、根尖乳头干细胞（SCAPs）和诱导多能干细胞（iPSCs）中对干细胞自我更新、增殖、分化、凋亡和代谢的调控作用。此外，iPSCs 和胚胎干细胞（ESCs）已被用作分析其在神经元发育方面功能的模型系统。SHANK 介导的干细胞命运决定是一个复杂的多因素过程。本研究旨在更好地理解 SHANK 在这些过程中的作用及其临床应用，从而推进干细胞治疗领域。本综述揭示了 SHANK 家族在干细胞命运中的调节作用。
