Organelle Cooperation in Stem Cell Fate: Lysosomes as Emerging Regulators of Cell Identity

Lisa M Julian; William L Stanford

doi:10.3389/fcell.2020.00591

Organelle Cooperation in Stem Cell Fate: Lysosomes as Emerging Regulators of Cell Identity

Front Cell Dev Biol. 2020 Jul 7:8:591. doi: 10.3389/fcell.2020.00591. eCollection 2020.

Authors

Lisa M Julian¹, William L Stanford^{2

3

4

5}

Affiliations

¹ Department of Biological Sciences, Simon Fraser University, Burnaby, BC, Canada.
² Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
³ Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
⁴ Ottawa Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
⁵ Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada.

Abstract

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.

Keywords: cancer stem cell (CSC); lysosomes; metabolism; neural crest (NC); neural stem cell (NSC); pluripotent stem cell (PSC); stem cell identity and fate.

Publication types

Review