Regulation of Stem Cell Functions Through Cyclic Adenosine Monophosphate (сAMP) Signaling: Mechanisms and Perspectives

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Abstract

Continuous renewal of body tissues is the key to maintaining the constancy of their function throughout a person'slife. Irreversible fading of tissue renewal processes over time underlies the development of age-associated diseases and determines the aging process. In addition, the development of socially significant diseases such as metabolic syndrome, type 2 diabetes, osteoporosis and many others is associated with the impaired tissue renewal. Postnatal stem cells play a decisive role in the process of tissue renewal and their adaptation to changing conditions. At the same time, a constant balance is maintained between the rate of cell growth and death throughout life. Disruption of this balance can lead to the development of both degenerative processes and oncological diseases. Therefore, the activity of stem cells is placed under strict control of the nervous and endocrine systems of the body. Despite the wide range of hormones and neurotransmitters acting on stem cells, the spectrum of intracellular signals that transmit information is extremely limited. Universal systems of second messengers generate unique cellular responses to different stimuli using specialized systems of signal tuning and modulation. One of the second messengers that ensure the transmission of intracellular signals is cyclic AMP synthesized by adenylate cyclase. This signaling pathway includes G protein-coupled receptors (GPCRs), various isoforms of adenylyl cyclases, as well as a wide range of scaffold and effector proteins. Working together, they ensure focusing of the cAMP signal and implement programs either to maintain stemness or, conversely, to trigger differentiation in various directions. The aim of our review is to provide a comprehensive view on the organization and compartmentalization of cAMP signaling in stem cells, as well as its participation in the regulation of the processes of maintaining the stemness and inducing differentiation in various directions.

About the authors

V. A. Usachev

Lomonosov Moscow State University

Email: usachjov-vova@mail.ru
ORCID iD: 0000-0003-1564-0644
postgraduate student Moscow

P. A. Tyurin-Kuzmin

Lomonosov Moscow State University

Email: tyurinkuzminpa@my.msu.ru
ORCID iD: 0000-0002-1901-1637
Dr. Sci. In Biology, Associate professor Moscow

A. A. Zinoveva

Lomonosov Moscow State University

Email: zinovevaanna356@gmail.com
ORCID iD: 0009-0007-3068-1678
postgraduate student Moscow

I. V. Zubarev

Moscow Institute of Physics and Technology

Email: ilyamitozubarev@gmail.com
ORCID iD: 0000-0002-7827-498X
PhD in Biology, senior scientific fellow, head of laboratory Dolgoprudny

K. Yu. Kulebyakin

Lomonosov Moscow State University

Email: konstantin-kuleb@mail.ru
ORCID iD: 0000-0001-6954-5787
PhD in Biology, Associate professor Moscow

M. V. Vorontsova

Lomonosov Moscow State University

Email: maria.v.vorontsova@mail.ru
ORCID iD: 0000-0002-9124-294X
PhD, MD, head of Laboratory of Molecular Endocrinology Moscow

V. A. Tkachuk

Lomonosov Moscow State University

Email: tkachuk@fbm.msu.ru
ORCID iD: 0000-0002-7492-747
Dr. Sci. In Biology, RAS academician, director Moscow

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