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Oct4GiP Reporter Assay to Study Genes that Regulate Mouse Embryonic Stem Cell Maintenance and Self-renewal
Published on: May 30, 2012
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Snail1-dependent control of embryonic stem cell pluripotency and lineage commitment
Yongshun Lin1, Xiao-Yan Li2, Amanda L Willis2
11] Division of Molecular Medicine and Genetics, Department of Internal Medicine, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA [2] Center for Molecular Medicine, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892, USA.
Nature Communications
|January 10, 2014
Summary
Snail1 regulates the stem cell transcriptome independently of Wnt signaling and epithelial-mesenchymal transition (EMT). However, during differentiation, Wnt-induced Snail1 controls neuroectodermal fate and mesoderm commitment.
Area of Science:
- Stem Cell Biology
- Developmental Biology
- Transcriptional Regulation
Background:
- Embryonic stem cells (ESCs) possess self-renewal and pluripotency, differentiating into all germ layers.
- Wnt signaling influences ESC maintenance, differentiation, and Snail1 expression.
- Snail1's role in ESC self-renewal, pluripotency, and lineage commitment is unclear.
Purpose of the Study:
- To investigate the function of Snail1 in embryonic stem cell self-renewal, pluripotency, and differentiation.
- To elucidate the relationship between Snail1, Wnt signaling, and epithelial-mesenchymal transition (EMT) in ESCs.
Main Methods:
- Utilized isogenic pairs of conditional knockout mouse ESCs.
- Analyzed Snail1's impact on the stem cell transcriptome.
- Examined Snail1's role during ESC differentiation, focusing on Wnt-mediated events.
Main Results:
- Snail1 controls the ESC transcriptome independently of Wnt signaling and EMT, without affecting self-renewal or pluripotency.
- During differentiation, Wnt-induced Snail1 is crucial for neuroectodermal fate determination.
- Snail1 plays a required role in epiblast stem cell exit and mesoderm lineage commitment.
Conclusions:
- Snail1 has distinct roles in maintaining ESC identity versus directing differentiation.
- Wnt-mediated Snail1 bursts are critical for lineage specification during early development.
- Snail1 is a key regulator of neuroectodermal and mesodermal fate decisions in differentiating ESCs.
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