Role of HIF1α Regulatory Factors in Stem Cells

Hypoxia-inducible factor 1 (HIF1) is a master transcription factor that induces the transcription of genes involved in the metabolism and behavior of stem cells. HIF1-mediated adaptation to hypoxia is required to maintain the pluripotency and survival of stem cells under hypoxic conditions. HIF1 activity is well known to be tightly controlled by the alpha subunit of HIF1 (HIF1α). Understanding the regulatory mechanisms that control HIF1 activity in stem cells will provide novel insights into stem cell biology under hypoxia. Recent research has unraveled the mechanistic details of HIF1α regulating processes, suggesting new strategies for regulating stem cells. This review summarizes recent experimental studies on the role of several regulatory factors (including calcium, 2-oxoglutarate-dependent dioxygenase, microtubule network, importin, and coactivators) in regulating HIF1α activity in stem cells.

Regulation of Stem Cell Fate by ROS-mediated Alteration of Metabolism

Stem cells have attracted much attention due to their distinct features that support infinite self-renewal and differentiation into the cellular derivatives of three lineages. Recent studies have suggested that many stem cells both embryonic and adult stem cells reside in a specialized niche defined by hypoxic condition. In this respect, distinguishing functional differences arising from the oxygen concentration is important in understanding the nature of stem cells and in controlling stem cell fate for therapeutic purposes. ROS act as cellular signaling molecules involved in the propagation of signaling and the translation of environmental cues into cellular responses to maintain cellular homeostasis, which is mediated by the coordination of various cellular processes, and to adapt cellular activity to available bioenergetic sources. Thus, in this review, we describe the physiological role of ROS in stem cell fate and its effect on the metabolic regulation of stem cells.