Evidence map›Paper›PMID 40446796›Full record

ArticleStem cell reports2025

Discovery of NANOG enhancers and their essential roles in self-renewal and differentiation in human embryonic stem cells.

Jielin Yan, Renhe Luo, Bess P Rosen, Dingyu Liu, Wilfred Wong, Christina S Leslie, Danwei Huangfu

Abstract read
In one paragraph

Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Jielin YanDevelopmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Renhe LuoDevelopmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Bess P RosenDevelopmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA; Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, New York, NY 10065, USA.
Dingyu LiuDevelopmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Wilfred WongTri-Institutional Training Program in Computational Biology and Medicine, Weill Cornell Medicine, New York, NY 10065, USA; Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Christina S LeslieComputational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Danwei HuangfuDevelopmental Biology Program, Sloan Kettering Institute, New York, NY 10065, USA. Electronic address: huangfud@mskcc.org.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Genomic control of gene regulatory networks governing early human lineagedecisionsU01HG012051 · NHGRI · SLOAN-KETTERING INST CAN RESEARCH · PI Michael A Beer, ANNA-KATERINA HADJANTONAKIS · 2021 to 2026
$8.3M
TRAINING PROGRAM IN MOLECULAR AND CELLULAR BIOLOGYT32GM008539 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI BROWN, ANTHONY M.C. · 1995 to 2020
$5.0M
Discovery of diabetes-relevant β cell enhancers through 4D enhancer mapping, integrative analysis, and large-scale CRISPRi perturbation screensU01DK128852 · NIDDK · SLOAN-KETTERING INST CAN RESEARCH · PI APOSTOLOU, EFFIE, HUANGFU, DANWEI · 2020 to 2024
$3.5M
NCI NIH HHS P30 CA008748NHGRI NIH HHS U01 HG012051NIDDK NIH HHS U01 DK128852NIGMS NIH HHS T32 GM008539
6 · The paper itself

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.

Indexed as

Cell DifferentiationCell Self RenewalEnhancer Elements, GeneticHuman Embryonic Stem CellsNanog Homeobox ProteinAnimalsCell LineCRISPR-Cas SystemsHumansMiceNanog Homeobox ProteinNANOG protein, humanCRISPRi screensenhancer deletionsenhancer duplicationsenhancersgenome architecturehESC differentiationhESCshuman embryonic stem cellsNANOGtranscriptional regulation

Identifiers

PMID40446796
PMCPMC12181961

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.