How and Why the Circadian Clock Regulates Proliferation of Adult Epithelial Stem Cells. 2023

Bogi Andersen, and Junyan Duan, and Satya Swaroop Karri
Division of Endocrinology, Department of Medicine, School of Medicine, University of California, Irvine, CA, USA.

First described in the early 20th century, diurnal oscillations in stem cell proliferation exist in multiple internal epithelia, including in the gastrointestinal tract, and in the epidermis. In the mouse epidermis, 3- to 4-fold more stem cells are in S-phase during the night than during the day. More recent work showed that an intact circadian clock intrinsic to keratinocytes is required for these oscillations in epidermal stem cell proliferation. The circadian clock also regulates DNA excision repair and DNA damage in epidermal stem cells in response to ultraviolet B radiation. During skin inflammation, epidermal stem cell proliferation is increased and diurnal oscillations are suspended. Here we discuss possible reasons for the evolution of this stem cell phenomenon. We argue that the circadian clock coordinates intermediary metabolism and the cell cycle in epidermal stem cells to minimize the accumulation of DNA damage from metabolism-generated reactive oxygen species. Circadian disruption, common in modern society, leads to asynchrony between metabolism and the cell cycle, and we speculate this will lead to oxidative DNA damage, dysfunction of epidermal stem cells, and skin aging.

UI MeSH Term Description Entries
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002940 Circadian Rhythm The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli. Diurnal Rhythm,Nyctohemeral Rhythm,Twenty-Four Hour Rhythm,Nycthemeral Rhythm,Circadian Rhythms,Diurnal Rhythms,Nycthemeral Rhythms,Nyctohemeral Rhythms,Rhythm, Circadian,Rhythm, Diurnal,Rhythm, Nycthemeral,Rhythm, Nyctohemeral,Rhythm, Twenty-Four Hour,Rhythms, Circadian,Rhythms, Diurnal,Rhythms, Nycthemeral,Rhythms, Nyctohemeral,Rhythms, Twenty-Four Hour,Twenty Four Hour Rhythm,Twenty-Four Hour Rhythms
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013234 Stem Cells Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells. Colony-Forming Units,Mother Cells,Progenitor Cells,Colony-Forming Unit,Cell, Mother,Cell, Progenitor,Cell, Stem,Cells, Mother,Cells, Progenitor,Cells, Stem,Colony Forming Unit,Colony Forming Units,Mother Cell,Progenitor Cell,Stem Cell
D015603 Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Keratinocyte
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D057906 Circadian Clocks Biological mechanism that controls CIRCADIAN RHYTHM. Circadian clocks exist in the simplest form in cyanobacteria and as more complex systems in fungi, plants, and animals. In humans the system includes photoresponsive RETINAL GANGLION CELLS and the SUPRACHIASMATIC NUCLEUS that acts as the central oscillator. Circadian Clock System,Circadian Timing System,Circadian Clock,Circadian Clock Systems,Circadian Timing Systems,Clock System, Circadian,Clock Systems, Circadian,Clock, Circadian,Clocks, Circadian,System, Circadian Clock,System, Circadian Timing,Systems, Circadian Clock,Systems, Circadian Timing,Timing System, Circadian,Timing Systems, Circadian

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