RRC ID 47710
Author Ogawa K, Saito A, Matsui H, Suzuki H, Ohtsuka S, Shimosato D, Morishita Y, Watabe T, Niwa H, Miyazono K.
Title Activin-Nodal signaling is involved in propagation of mouse embryonic stem cells.
Journal J Cell Sci
Abstract Embryonic stem (ES) cells are self-renewing cells that maintain pluripotency to differentiate into all types of cells. Because of their potential to provide a variety of tissues for use in regenerative medicine, there is great interest in the identification of growth factors that govern these unique properties of ES cells. However, the signaling pathways controlling ES cell proliferation remain largely unknown. Since transforming growth factor beta (TGFbeta) superfamily members have been implicated in the processes of early embryogenesis, we investigated their roles in ES cell self-renewal. Inhibition of activin-Nodal-TGFbeta signaling by Smad7 or SB-431542 dramatically decreased ES cell proliferation without decreasing ES pluripotency. By contrast, inhibition of bone morphogenetic protein (BMP) signaling by Smad6 did not exhibit such effects, suggesting that activin-Nodal-TGFbeta signaling, but not BMP signaling, is indispensable for ES cell propagation. In serum-free culture, supplementation of recombinant activin or Nodal, but not TGFbeta or BMP, significantly enhanced ES cell propagation without affecting pluripotency. We also found that activin-Nodal signaling was constitutively activated in an autocrine fashion in serum-free cultured ES cells, and that inhibition of such endogenous signaling by SB-431542 decreased ES cell propagation in serum-free conditions. These findings suggest that endogenously activated autocrine loops of activin-Nodal signaling promote ES cell self-renewal.
Volume 120(Pt 1)
Pages 55-65
Published 2007-1-1
DOI 10.1242/jcs.03296
PII 120/1/55
PMID 17182901
MeSH Activins / metabolism* Activins / pharmacology Animals Autocrine Communication / drug effects Autocrine Communication / physiology Benzamides / pharmacology Cell Division / physiology Chimera Culture Media, Serum-Free / pharmacology Dioxoles / pharmacology Embryonic Stem Cells / cytology* Embryonic Stem Cells / metabolism* Mice Mice, Inbred C57BL Mice, Nude Nodal Protein Protein Kinase Inhibitors / pharmacology Signal Transduction / drug effects Signal Transduction / physiology* Smad6 Protein / genetics Smad6 Protein / metabolism Smad7 Protein / genetics Smad7 Protein / metabolism Teratoma Transforming Growth Factor beta / metabolism* Transforming Growth Factor beta / pharmacology Tumor Cells, Cultured
IF 4.517
Times Cited 140
DNA material pBR-PyCAG-fSmad7DsRedT4-IPG (RDB10704)