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Cellular therapy exerts profound therapeutic potential for curing a broad spectrum of diseases. Adult stem cells reside within a specified dynamic niche in vivo, which is essential for continuous tissue homeostatic maintenance through balancing self-renewal with lineage selection. Meanwhile, adult stem cells may be multipotent or unipotent, and are present in both quiescent and actively dividing states in vivo of the mammalians, which may switch to each other state in response to biophysical cues through mitochondria-mediated mechanisms, such as alterations in mitochondrial respiration and metabolism. In general, stem cells facilitate tissue repair after tissue-specific homing through various mechanisms, including immunomodulation of local microenvironment, differentiation into functional cells, cell “empowerment” via paracrine secretion, immunoregulation, and intercellular mitochondrial transfer. Interestingly, cell-source-specific features have been reported between different tissue-derived adult stem cells with distinct functional properties due to the different microenvironments in vivo, as well as differential functional properties in different tissue-derived stem cell-derived extracellular vehicles, mitochondrial metabolism, and mitochondrial transfer capacity. Here, we summarized the current understanding on roles of mitochondrial dynamics during stem cell homeostasis and aging, and lineage-specific differentiation. Also, we proposed potential unique mitochondrial molecular signature features between different source-derived stem cells and potential associations between stem cell aging and mitochondria–endoplasmic reticulum (ER) communication, as well as potential novel strategies for anti-aging intervention and healthy aging.

Dynamic regulation of mitochondrial-endoplasmic reticulum crosstalk during stem cell homeostasis and aging