bims-ciryme 2023-06-04 papers

Issue of 2023‒06‒04
two papers selected by
Gabriela Da Silva Xavier
University of Birmingham

Cell Rep. 2023 Jun 01. pii: S2211-1247(23)00599-5. [Epub ahead of print]42(6): 112588

Liver and muscle circadian clocks cooperate to support glucose tolerance in mice.

Physiology is regulated by interconnected cell and tissue circadian clocks. Disruption of the rhythms generated by the concerted activity of these clocks is associated with metabolic disease. Here we tested the interactions between clocks in two critical components of organismal metabolism, liver and skeletal muscle, by rescuing clock function either in each organ separately or in both organs simultaneously in otherwise clock-less mice. Experiments showed that individual clocks are partially sufficient for tissue glucose metabolism, yet the connections between both tissue clocks coupled to daily feeding rhythms support systemic glucose tolerance. This synergy relies in part on local transcriptional control of the glucose machinery, feeding-responsive signals such as insulin, and metabolic cycles that connect the muscle and liver. We posit that spatiotemporal mechanisms of muscle and liver play an essential role in the maintenance of systemic glucose homeostasis and that disrupting this diurnal coordination can contribute to metabolic disease.

Keywords: Bmal1; CP: Metabolism; autonomy; circadian rhythms; endocrinology; glucose; inter-organ crosstalk; liver; metabolism; muscle; systems biology

DOI: https://doi.org/10.1016/j.celrep.2023.112588

Cell Rep. 2023 May 31. pii: S2211-1247(23)00601-0. [Epub ahead of print]42(6): 112590

The circadian clock CRY1 regulates pluripotent stem cell identity and somatic cell reprogramming.

Shogo Sato, Tomoaki Hishida, Kenichiro Kinouchi, Fumiaki Hatanaka, Yumei Li, Quy Nguyen, Yumay Chen, Ping H Wang, Kai Kessenbrock, Wei Li, Juan Carlos Izpisua Belmonte, Paolo Sassone-Corsi.

Distinct metabolic conditions rewire circadian-clock-controlled signaling pathways leading to the de novo construction of signal transduction networks. However, it remains unclear whether metabolic hallmarks unique to pluripotent stem cells (PSCs) are connected to clock functions. Reprogramming somatic cells to a pluripotent state, here we highlighted non-canonical functions of the circadian repressor CRY1 specific to PSCs. Metabolic reprogramming, including AMPK inactivation and SREBP1 activation, was coupled with the accumulation of CRY1 in PSCs. Functional assays verified that CRY1 is required for the maintenance of self-renewal capacity, colony organization, and metabolic signatures. Genome-wide occupancy of CRY1 identified CRY1-regulatory genes enriched in development and differentiation in PSCs, albeit not somatic cells. Last, cells lacking CRY1 exhibit differential gene expression profiles during induced PSC (iPSC) reprogramming, resulting in impaired iPSC reprogramming efficiency. Collectively, these results suggest the functional implication of CRY1 in pluripotent reprogramming and ontogenesis, thereby dictating PSC identity.

Keywords: CP: Stem cell research; Cryptochrome 1; circadian clock; iPSC reprogramming; metabolism; pluripotent stem cells; stem cell research; sterol regulatory element binding protein 1

DOI: https://doi.org/10.1016/j.celrep.2023.112590