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

Cell Reports (Jun 2023)

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

Affiliations

Shogo Sato: Center for Epigenetics and Metabolism, Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA, USA; Center for Biological Clocks Research, Department of Biology, Texas A&M University, College Station, TX, USA; Corresponding author
Tomoaki Hishida: Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA; Laboratory of Biological Chemistry, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan
Kenichiro Kinouchi: Center for Epigenetics and Metabolism, Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA, USA
Fumiaki Hatanaka: Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA; Altos Labs, San Diego, CA, USA
Yumei Li: Division of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA, USA
Quy Nguyen: Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA, USA
Yumay Chen: UC Irvine Diabetes Center, Sue and Bill Gross Stem Cell Research Center, Department of Medicine, University of California, Irvine, Irvine, CA, USA
Ping H. Wang: UC Irvine Diabetes Center, Sue and Bill Gross Stem Cell Research Center, Department of Medicine, University of California, Irvine, Irvine, CA, USA
Kai Kessenbrock: Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA, USA
Wei Li: Division of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA, USA
Juan Carlos Izpisua Belmonte: Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA; Altos Labs, San Diego, CA, USA; Corresponding author
Paolo Sassone-Corsi: Center for Epigenetics and Metabolism, Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA, USA

Journal volume & issue: Vol. 42, no. 6
p. 112590

Abstract

Read online

Summary: 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.

CP: Stem cell research

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

About the journal

Abstract

Keywords