A review on transcriptional regulation responses to hypoxia in mesenchymal stem cells

Mesenchymal stem cells (MSCs), which are known for having therapeutic applications, reside in stem cell niches where the oxygen concentration is low. At the molecular level, the master regulator of the cellular reaction to hypoxia is hypoxia-inducible transcription factor (HIF). The transcriptional response of a cell to hypoxia is affected by two major components; first, the structure of hypoxia-response elements (HREs), which primarily define how much of the HIF signal is integrated into the transcriptional output of individual genes. Second, the availability of other transcriptional factors cooperating with HIF in the context of HRE. In MSCs, the expression of a single gene by hypoxia depends on elements such as factors influencing the HIF activity, metabolic pathways, the real oxygen concentration in the cellular microenvironment, and duration of culture. In addition, specific growth factors and pro-infection cytokines, hormones, oncogenic signaling, as well as ultrasound are potent regulators of HIF in MSCs. Altogether, the response of MSCs to hypoxia is complex and mediated by several genes and molecular agents. Regarding the influence of hypoxia on MSCs, oxygen concentration must be taken into consideration based on the cell type and the aim of culture before a particular MSCs culture.