Loss of epigenetic polarity is a hallmark of hematopoietic stem cell aging.

Changes of polarity in somatic stem cells upon aging or disease lead to a functional deterioration of stem cells and consequently loss of tissue homeostasis, likely due to changes in the mode (symmetry versus asymmetry) of stem cell divisions. Changes in polarity of epigenetic markers (or 'epi-polarity') in stem cells, which are linked to alterations in chromatin architecture, might explain how a decline in the frequency of epipolar stem cells can have a long-lasting impact on the function of especially aging stem cells. The drift in epipolarity might represent a novel therapeutic target to improve stem cell function upon aging or disease. Here we review basic biological principles of epigenetic polarity, with a special focus on epipolarity and aging of hematopoietic stem cells.