Time-dependent clock gene expression in mouse and human stem and progenitor cells
Tsinkalovsky, O.; Smaaland, R.; Rosenlund, B.; Sothern, R. B.; Hirt, A.; Steine, S.; Badee, A.; Abrahamsen, J. F.; Eiken, H. G. and Laerum, O. D., (2007), Circadian variations in clock gene expression of human bone marrow CD34-positive cells. Preprint. To be published in Journal of Bioogical Rhythms. Copyright Sage Publications. http://dx.doi.org/10.1177/0748730406299078 (369.3Kb)
Experimental Hematology 34, Tsinkalovsky, O.; Filipski, E.; Rosenlund, B.; Sothern, R. B.; Eiken, H. G.; Wu, M. W.; Claustrat, B.; Bayer, J.; Levi, F. and Laerum, O. D., Circadian expression of clock genes in purified hematopoietic stem cells is developmentally regulated in mouse bone marrow, pp. 1248-1260. Copyright 2005 International Society for Experimental Hematology. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.exphem.2006.05.008 (445.3Kb)
Experimental Hematology 33, Tsinkalovsky, O.; Rosenlund, B.; Laerum, O. D. and Eiken, H. G., Clock gene expression in purified mouse hematopoietic stem cells, pp. 100-107. Copyright 2005 International Society for Experimental Hematology. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.exphem.2004.09.007 (268.0Kb)
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Time is a fundamental part of all biological processes. During the whole process of evolution, living cells and organisms had to adapt to cyclic variations in the environment. In particular, the light and temperature conditions varied with day and night and with the seasons. The cellular functions and behavior in organisms were regulated according to their daily needs and provision of optimal conditions for survival. Time functions in cells are of two kinds. One is the cyclic variation, where the same events come back with regular intervals. Thereby, cellular adaptation occurs in a cyclic manner. The second way is longitudinal time regulation. From conception on, the development of organs occur sequentially and strictly coordinated in time until a mature fetus is ready for delivery. The periods of gestation, infant, growth and maturity, as well as aging, are strictly regulated in all higher organisms. Total life span is also rather constant within each species, although there are differences of many fold between short-lived and long-lived species. Thus, all the different longitudinal time periods in the life within a species are strictly coordinated to each other and are in concordance with total life span. Time regulation in single cells occurs at shorter intervals, both with cyclic and noncyclic variations. The oscillations may be down to a few seconds or even parts of seconds, such as nerve pulses. Heartbeat in higher organisms usually occurs as a rhythm of about one second or less, respiratory rhythm is slower, while the rhythm of the blood pressure is according to day and night. As a result, many types of time regulation and adaptation are occurring simultaneously in the same organism. Until a few years ago, the study of such time keeping was largely confined to the observation of phenomena from the outside and with mainly a descriptive approach. This has been replaced by a deeper understanding of the underlying biology and regulatory mechanisms at the genetic level (for recent review see Koukkari and Sothern, 2006b). This thesis deals with the hematopoietic system in mice and in men, a highly adaptable tissue with a high cell turnover and many different functions that cover all parts of the body. It is therefore no wonder that time keeping is an important part of the regulatory circuits. The main emphasis of this thesis is on the elucidation of local clock functions in cells of different stage of maturation, and discussion on how the molecular clock in bone marrow (BM) is unique compared to other tissues, as well as different between species.