重编程
诱导多能干细胞
生物
体细胞
细胞生物学
生物钟
干细胞
遗传学
细胞
基因
胚胎干细胞
作者
Shogo Sato,Tomoaki Hishida,Kenichiro Kinouchi,Fumiaki Hatanaka,Yumei Li,Quy Nguyen,Yumay Chen,Ping H. Wang,Kai Kessenbrock,Wei Li,Juan Carlos Izpisúa Belmonte,Paolo Sassone‐Corsi
出处
期刊:Cell Reports
[Elsevier]
日期:2023-06-01
卷期号:42 (6): 112590-112590
标识
DOI:10.1016/j.celrep.2023.112590
摘要
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.
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