Journal
CELL
Volume 165, Issue 2, Pages 410-420Publisher
CELL PRESS
DOI: 10.1016/j.cell.2016.02.014
Keywords
-
Categories
Funding
- California Institute for Regenerative Medicine (CIRM) grant [CL1-00521]
- Rainwater Charitable Foundation
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- CIRM [TG2-01151]
Ask authors/readers for more resources
Under defined differentiation conditions, human embryonic stem cells (hESCs) can be directed toward a mesendoderm (ME) or neuroectoderm (NE) fate, the first decision during hESC differentiation. Coupled with lineage-specific G1 lengthening, a divergent ciliation pattern emerged within the first 24 hr of induced lineage specification, and these changes heralded a neuroectoderm decision before any neural precursor markers were expressed. By day 2, increased ciliation in NE precursors induced autophagy that resulted in the inactivation of Nrf2 and thereby relieved transcriptional activation of OCT4 and NANOG. Nrf2 binds directly to upstream regions of these pluripotency genes to promote their expression and repress NE derivation. Nrf2 suppression was sufficient to rescue poorly neurogenic iPSC lines. Only after these events had been initiated did neural precursor markers get expressed at day 4. Thus, we have identified a primary cilium-autophagy-Nrf2 (PAN) control axis coupled to cell-cycle progression that directs hESCs toward NE.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available