TY - JOUR
T1 - AICAR activates the pluripotency transcriptional network in embryonic stem cells and induces KLF4 and KLF2 expression in fibroblasts
AU - Adamo, Luigi
AU - Zhang, Yuzhi
AU - García-Cardeña, Guillermo
N1 - Funding Information:
This work was supported by a grant from the Defence Threat Reduction Agency - Joint Science and Technology Office, Medical S&T Division (to PR) and partly by DARPA GRANT W911NF-07-1-0623 (to BRS).
PY - 2009/2/12
Y1 - 2009/2/12
N2 - Background: Pluripotency, the property of a cell to differentiate into all cellular types of a given organism, is central to the development of stem cell-based therapies and regenerative medicine. Stem cell pluripotency is the result of the orchestrated activation of a complex transcriptional network characterized by the expression of a set of transcription factors including the master regulators of pluripotency Nanog and Oct4. Recently, it has been shown that pluripotency can be induced in somatic cells by viral-mediated expression of the transcription factors Oct3/4, Sox2, Klf4, and c-Myc. Results: Here we show that 5-Aminoimidazole-4-carboxamide-1-b-riboside (AICAR) is able to activate the molecular circuitry of pluripotency in mouse embryonic stem cells (mESC) and maintain Nanog and Oct4 expression in mESC exposed to the differentiating agent retinoic acid. We also show that AICAR is able to induce Klf4, Klf2 and Myc expression in both mESC and murine fibroblasts. Conclusion: AICAR is able to activate the molecular circuitry of pluripotency in mESC and to induce the expression of several key regulators of pluripotency in somatic cells. AICAR is therefore a useful pharmacological entity for studying small molecule mediated induction of pluripotency.
AB - Background: Pluripotency, the property of a cell to differentiate into all cellular types of a given organism, is central to the development of stem cell-based therapies and regenerative medicine. Stem cell pluripotency is the result of the orchestrated activation of a complex transcriptional network characterized by the expression of a set of transcription factors including the master regulators of pluripotency Nanog and Oct4. Recently, it has been shown that pluripotency can be induced in somatic cells by viral-mediated expression of the transcription factors Oct3/4, Sox2, Klf4, and c-Myc. Results: Here we show that 5-Aminoimidazole-4-carboxamide-1-b-riboside (AICAR) is able to activate the molecular circuitry of pluripotency in mouse embryonic stem cells (mESC) and maintain Nanog and Oct4 expression in mESC exposed to the differentiating agent retinoic acid. We also show that AICAR is able to induce Klf4, Klf2 and Myc expression in both mESC and murine fibroblasts. Conclusion: AICAR is able to activate the molecular circuitry of pluripotency in mESC and to induce the expression of several key regulators of pluripotency in somatic cells. AICAR is therefore a useful pharmacological entity for studying small molecule mediated induction of pluripotency.
UR - http://www.scopus.com/inward/record.url?scp=62349090391&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=62349090391&partnerID=8YFLogxK
U2 - 10.1186/1471-2210-9-12
DO - 10.1186/1471-2210-9-12
M3 - Article
C2 - 19216758
AN - SCOPUS:62349090391
SN - 1471-2210
VL - 9
JO - BMC Pharmacology
JF - BMC Pharmacology
M1 - 12
ER -