Discovery of NANOG enhancers and their essential roles in self-renewal and differentiation in human embryonic stem cells Journal Article
| Authors: | Yan, J.; Luo, R.; Rosen, B. P.; Liu, D.; Wong, W.; Leslie, C. S.; Huangfu, D. |
| Article Title: | Discovery of NANOG enhancers and their essential roles in self-renewal and differentiation in human embryonic stem cells |
| Abstract: | Human embryonic stem cells (hESCs) are notable for their ability to self-renew and to differentiate into all tissue types in the body. NANOG is a core regulator of hESC identity, and dynamic control of its expression is crucial to maintain the balance between self-renewal and differentiation. Transcriptional regulation depends on enhancers, but NANOG enhancers in hESCs are not well characterized. Here, we report two NANOG enhancers discovered from a CRISPR interference screen in hESCs. Deletion of a single copy of either enhancer significantly reduced NANOG expression, compromising self-renewal and increasing differentiation propensity. Interestingly, these two NANOG enhancers are involved in a tandem duplication event found in certain primates including humans but not in mice. However, the duplicated counterparts do not regulate NANOG expression. This work expands our knowledge of functional enhancers in hESCs and highlights the sensitivity of the hESC state to the dosage of core regulators and their enhancers. © 2025 The Author(s) |
| Keywords: | controlled study; human cell; genetics; mouse; animal; cytology; metabolism; animals; mice; gene expression; embryo; cell line; cell differentiation; transcription factor nanog; pharmacology; transcriptional regulation; enhancer region; enhancer elements, genetic; human embryonic stem cells; enhancers; cell self-renewal; nanog; cell self renewal; humans; human; article; crispr cas system; genome architecture; crispr-cas systems; human embryonic stem cell; hescs; nanog homeobox protein; crispri screens; enhancer deletions; enhancer duplications; hesc differentiation; nanog protein, human |
| Journal Title: | Stem Cell Reports |
| Volume: | 20 |
| Issue: | 6 |
| ISSN: | 2213-6711 |
| Publisher: | Cell Press |
| Date Published: | 2025-01-01 |
| Start Page: | 102511 |
| Language: | English |
| DOI: | 10.1016/j.stemcr.2025.102511 |
| PUBMED: | 40446796 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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