Circadian control of tissue homeostasis and adult stem cells.

The circadian timekeeping mechanism adapts physiology to the 24-hour light/dark cycle. However, how the outputs of the circadian clock in different peripheral tissues communicate and synchronize each other is still not fully understood. The circadian clock has been implicated in the regulation of numerous processes, including metabolism, the cell cycle, cell differentiation, immune responses, redox homeostasis, and tissue repair. Accordingly, perturbation of the machinery that generates circadian rhythms is associated with metabolic disorders, premature ageing, and various diseases including cancer. Importantly, it is now possible to target circadian rhythms through systemic or local delivery of time cues or compounds. Here, we summarize recent findings in peripheral tissues that link the circadian clock machinery to tissue-specific functions and diseases

Where do you come from; where do you go? Pluripotency, differentiation and malfunction of stem cells

The international conference 'Stem Cells in Development and Disease' took place in September 2011 at the Max-Delbrueck-Center for Molecular Medicine (MDC) in Berlin. It brought together scientists working on different types of stem cell and covered the latest findings in stem cell biology, including the genetic and epigenetic mechanisms of reprogramming, maintenance of pluripotency and differentiation

Immunometabolism at the crossroads of obesity and cancer-a Keystone Symposia report.

Immunometabolism considers the relationship between metabolism and immunity. Typically, researchers focus on either the metabolic pathways within immune cells that affect their function or the impact of immune cells on systemic metabolism. A more holistic approach that considers both these viewpoints is needed. On September 5-8, 2022, experts in the field of immunometabolism met for the Keystone symposium "Immunometabolism at the Crossroads of Obesity and Cancer" to present recent research across the field of immunometabolism, with the setting of obesity and cancer as an ideal example of the complex interplay between metabolism, immunity, and cancer. Speakers highlighted new insights on the metabolic links between tumor cells and immune cells, with a focus on leveraging unique metabolic vulnerabilities of different cell types in the tumor microenvironment as therapeutic targets and demonstrated the effects of diet, the microbiome, and obesity on immune system function and cancer pathogenesis and therapy. Finally, speakers presented new technologies to interrogate the immune system and uncover novel metabolic pathways important for immunity

Integration of feeding behavior by the liver circadian clock reveals network dependency of metabolic rhythms

The mammalian circadian clock, expressed throughout the brain and body, controls daily metabolic homeostasis. Clock function in peripheral tissues is required, but not sufficient, for this task. Because of the lack of specialized animal models, it is unclear how tissue clocks interact with extrinsic signals to drive molecular oscillations. Here, we isolated the interaction between feeding and the liver clock by reconstituting Bmal1 exclusively in hepatocytes (Liver-RE), in otherwise clock-less mice, and controlling timing of food intake. We found that the cooperative action of BMAL1 and the transcription factor CEBPB regulates daily liver metabolic transcriptional programs. Functionally, the liver clock and feeding rhythm are sufficient to drive temporal carbohydrate homeostasis. By contrast, liver rhythms tied to redox and lipid metabolism required communication with the skeletal muscle clock, demonstrating peripheral clock cross-talk. Our results highlight how the inner workings of the clock system rely on communicating signals to maintain daily metabolism.C.M.G. was supported by the National Cancer Institute of the National Institutes of Health (NIH) under award number T32CA009054 and by the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement 749869. K.B.K. was supported by NIH-NINDS F32DK121425, and J.G.S. was supported by the Zymo-CEM Postdoctoral Fellowship (Zymo Research). P.P. was supported by a scholarship from the Wenner-Gren Foundations. C.V. and M.M.S. are supported by NIH grants DK20AU4084 and HL138193.The work of S.C., M.S., and P.B. was in part supported by NIH grant GM123558 to P.B. Work in the W.L. laboratory was supported by NIH grants R01HG007538, R01CA193466, and R01CA228140. Work in the P.S.-C. laboratory is supported by NIH grants R21DK114652 and R21AG053592, a Challenge Grant from the Novo Nordisk Foundation (NNF-202585), and through access to the Genomics High Throughput Facility Shared Resource of the Cancer Center Support Grant (CA-62203) at the UCI and NIH-shared instrumentation grants 1S10RR025496-01, 1S10OD010794-01, and 1S10OD021718-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. P.-S.W. is supported by a “Ramon y Cajal” contract (RYC2019-026661-I) from the Spanish Ministry of Science and Innovation (MICINN). Research in the P.M.-C. laboratory is supported by MINECO-Spain (RTI2018-096068), ERC-2016-AdG-741966, AFM, MDA-USA, La Marató/TV3 Foundation, LaCaixa-HEALTH-HR17-00040, and UPGRADE-H2020-825825 and María-de-Maeztu-Program for Units of Excellence to UPF (MDM-2014-0370) and Severo-Ochoa-Program for Centers of Excellence to CNIC (SEV-2015-0505). Research in the S.A.B. laboratory is supported by the European Research Council (ERC), the Government of Cataluña (SGR grant), the Government of Spain (MINECO), the La Marató/TV3 Foundation, and The Worldwide Cancer Research Foundation (WCRF). Author contributions: C.M.G., K.B.K., J.G.S., P.B., S.M., S.A.B., P.M.-C., and P.S.-C. conceived and designed the study. C.M.G., K.B.K., J.G.S., S.A.B., P.M.-C., and P.S.-C. wrote and edited the manuscript. C.M.G., K.B.K., J.G.S., P.-S.W., V.M.Z., T.M., K.S., T.S., P.P., S.K.C., and K.A.D. performed experiments. O.D., A.K. and M.V.-D. provided technical support. D.L., J.M.M.K., C.V., and M.M.S. performed bioinformatic correlation analyses. S.C., M.S., P.K., R.C., J.S., and W.L. performed sequencing analysis