Regulation of stem cell fate is best understood at the level of gene and protein regulatory networks, though it is now clear that multiple cellular organelles also have critical impacts. A growing appreciation for the functional interconnectedness of organelles suggests that an orchestration of integrated biological networks functions to drive stem cell fate decisions and regulate metabolism. Metabolic signaling itself has emerged as an integral regulator of cell fate including the determination of identity, activation state, survival, and differentiation potential of many developmental, adult, disease, and cancer-associated stem cell populations and their progeny. As the primary adenosine triphosphate-generating organelles, mitochondria are well-known regulators of stem cell fate decisions, yet it is now becoming apparent that additional organelles such as the lysosome are important players in mediating these dynamic decisions. In this review, we will focus on the emerging role of organelles, in particular lysosomes, in the reprogramming of both metabolic networks and stem cell fate decisions, especially those that impact the determination of cell identity. We will discuss the inter-organelle interactions, cell signaling pathways, and transcriptional regulatory mechanisms with which lysosomes engage and how these activities impact metabolic signaling. We will further review recent data that position lysosomes as critical regulators of cell identity determination programs and discuss the known or putative biological mechanisms. Finally, we will briefly highlight the potential impact of elucidating mechanisms by which lysosomes regulate stem cell identity on our understanding of disease pathogenesis, as well as the development of refined regenerative medicine, biomarker, and therapeutic strategies.

干细胞命运的调节最好在基因和蛋白质调节网络水平上理解，尽管现在很清楚多个细胞器也具有关键影响。人们对细胞器功能互连性的日益认识表明，整合的生物网络的协调可以驱动干细胞的命运决定和调节新陈代谢。代谢信号本身已成为细胞命运的整体调节剂，包括许多发育、成体、疾病和癌症相关干细胞群及其后代的身份、激活状态、存活和分化潜力的确定。作为产生三磷酸腺苷的主要细胞器，线粒体是众所周知的干细胞命运决定的调节者，但现在越来越明显的是，溶酶体等其他细胞器在调节这些动态决定中发挥着重要作用。在这篇综述中，我们将重点关注细胞器（特别是溶酶体）在代谢网络重编程和干细胞命运决定中的新兴作用，特别是那些影响细胞身份决定的细胞器。我们将讨论溶酶体参与的细胞器间相互作用、细胞信号传导途径和转录调节机制，以及这些活动如何影响代谢信号传导。我们将进一步回顾最近的数据，这些数据将溶酶体定位为细胞身份确定程序的关键调节剂，并讨论已知或假定的生物学机制。 最后，我们将简要强调阐明溶酶体调节干细胞身份的机制对我们理解疾病发病机制以及精细再生医学、生物标志物和治疗策略的发展的潜在影响。