期刊
EXPERIMENTAL CELL RESEARCH
卷 312, 期 13, 页码 2538-2546出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2006.04.010
关键词
ES cell; LIF signaling; JAK-STAT pathway; nuclear receptor; PPAR gamma agonist
资金
- NCI NIH HHS [5R21CA106207-02] Funding Source: Medline
- NINDS NIH HHS [5R01NS042257-01A3, 3R01NS042257-01A2S1] Funding Source: Medline
Embryonic stem (ES) cells are genetically normal, pluripotent cells, capable of self-renewal and differentiation into all cell lineages. While leukemia inhibitory factor (LIF) maintains pluripotency in mouse ES cells, retinoic acid and other nuclear hormones induce neuro-glial differentiation in mouse and human ES cells in culture. Peroxisome-proliferator-activated receptors (PPARs) are ligand-dependent nuclear receptor transcription factors that regulate cell growth and differentiation in many cell types. However, the role of PPARs in the regulation of ES cell growth and differentiation is not known. In this study, we show that LIF induces proliferation and self-renewal of mouse D3-ES cells in culture. However, treatment with 15-Deoxy-Delta(12,14)-Prostaglandin J(2) (15d-PGJ2), a natural ligand for PPAR gamma, or all-trans retinoic acid (ATRA) results in a dose-dependent decrease in proliferation and self-renewal in D3-ES cells. Immunoprecipitation and Western blot analyses showed that LIF induces tyrosine phosphorylation of JAK1, TYK2 and STAT3 in 30 min and treatment with 15d-PGJ2 or ATRA results in a dose-dependent decrease in LIF-induced phosphorylation of JAK1 and STAT3 in D3-ES cells. However, treatment of D3-ES cells with Ciglitazone or 15d-PGJ2 for 48 h in culture resulted in a dose-dependent increase in PPAR gamma protein expression. These results suggest that PPAR gamma agonists regulate LIF signaling through JAK-STAT pathway leading to growth and self-renewal of ES cells. (c) 2006 Elsevier Inc. All rights reserved.
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