TGF-β control of stem cell differentiation genes.
The canonical TGF-β/Smad signaling pathway was delineated in the mid 90s and enriched over the past decade with many findings about its specificity, regulation, networking, and malfunctions in disease. However, a growing understanding of the chromatin status of a critical class of TGF-β target genes - the genes controlling differentiation of embryonic stem cells - recently prompted a reexamination of this pathway and its critical role in the regulation of stem cell differentiation. The new findings reveal master regulators of the pluripotent state set the stage for Smad-mediated activation of master regulators of the next differentiation stage. Furthermore, a novel branch of the TGF-β/Smad pathway has been identified in which a chromatin-reading Smad complex makes the master differentiation genes accessible to canonical Smad complexes for transcriptional activation. These findings provide exciting new insights into the global role of TGF-β signaling in the regulators of stem cell fate.
Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. j-massague@ski.mskcc.org
Joan
J
Massagué
Qiaoran
Q
Xi
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002843:Chromatin / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D002843:Chromatin; D008024:Ligands; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; C511956:TRIM33 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta