Evidence map›Paper›PMID 41549316›Full record

ArticleInflammation and regeneration2026

Pivotal contribution of super-enhancer-driven KLF6 expression to the adipogenesis of human adipose-derived stem cells.

Mai-Phuong Nguyen, Kaoru Yamagata, Anh Phuong Nguyen, Tong Zhang, Hidenori Sakai, Uyen Thi Ngo, Yu Shan, Takashi Otsuka, Ngo Thi Dieu Huong, Takafumi Aritomi and 4 more

Abstract read
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In one paragraph

Article in Inflammation and regeneration, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
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0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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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

14 authors.

Mai-Phuong NguyenThe First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-Nishi-Ku, Kitakyushu, Fukuoka, 807-8555, Japan.ORCID http://orcid.org/0000-0001-9419-5766
Kaoru YamagataThe First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-Nishi-Ku, Kitakyushu, Fukuoka, 807-8555, Japan.
Anh Phuong NguyenEndocrinology and Diabetes Department, Bach Mai Hospital, Hanoi, Vietnam.
Tong ZhangWest China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
Hidenori SakaiThe First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-Nishi-Ku, Kitakyushu, Fukuoka, 807-8555, Japan.
Uyen Thi NgoThe First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-Nishi-Ku, Kitakyushu, Fukuoka, 807-8555, Japan.
Yu ShanDepartment of Pediatrics, Shenyang Women's and Children's Hospital, Shenyang Clinical Medical Research Center for Genetic Disease Diagnosis, Shenyang, China.
Takashi OtsukaThe First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-Nishi-Ku, Kitakyushu, Fukuoka, 807-8555, Japan.
Ngo Thi Dieu HuongThe First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-Nishi-Ku, Kitakyushu, Fukuoka, 807-8555, Japan.
Takafumi AritomiThe First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-Nishi-Ku, Kitakyushu, Fukuoka, 807-8555, Japan.
Meng YuanThe First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-Nishi-Ku, Kitakyushu, Fukuoka, 807-8555, Japan.
Shigeaki KatoGraduate School of Life Science and Engineering, Iryo Sosei University, Fukushima, Japan.
Yoshiya TanakaThe First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-Nishi-Ku, Kitakyushu, Fukuoka, 807-8555, Japan.
Shingo NakayamadaThe First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-Nishi-Ku, Kitakyushu, Fukuoka, 807-8555, Japan. s-nakaya@med.uoeh-u.ac.jp.ORCID http://orcid.org/0000-0002-2209-8454

Funding

Ministry of Education, Culture, Sports, Science and Technology (JP) JSPS KAKENHI #22K08536
6 · The paper itself

Abstract

backgroundSuper-enhancers (SEs), characterized by dense clusters of enhancer elements enriched with transcriptional activator binding sites, are involved in cell differentiation. However, little is known about SE-mediated regulation of adipogenic genes. The aim of this study was to elucidate the functional role of the KLF6-proximal SE during the adipogenesis of human adipose-derived stem cells (hADSCs).

methodsAdipogenic induction medium (AIM) was used for differentiation of hADSCs into adipocytes, which were evaluated for adipogenic gene expression and adipogenesis using quantitative PCR and Oil Red O (ORO) staining, respectively. The effects of SE inhibitors, locked nucleic acid-mediated enhancer RNA (eRNA) knockdown, and small interfering RNA-mediated knockdown of KLF6 on adipogenesis and adipogenic gene levels were evaluated. Chromatin immunoprecipitation assays were performed to identify transcriptional regulators binding to the promoter regions of KLF6 and the adipogenesis-inhibitory Delta-like non-canonical Notch ligand 1 (DLK1) gene during adipogenesis.

resultsIn silico screening identified KLF6 as an obesity-susceptibility gene associated with single-nucleotide polymorphisms and located within the domain of SE_00159, which was activated in adipocytes. AIM-cultured hADSCs exhibited time-dependent increases in KLF6 mRNA and protein expression. During adipogenesis, the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) bound to the KLF6 promoter. Treatment with the SE inhibitor JQ1 resulted in a dose-dependent decrease in KLF6 mRNA expression and reduced ORO staining. Knockdown of eRNA expressed from the SE_00159 domain decreased KLF6 levels during adipogenesis. Consistently, KLF6 knockdown during hADSC adipogenesis downregulated the adipogenic genes PPARG and CEBPA, while upregulating DLK1. Additionally, KLF6 together with histone deacetylase (HDAC)3 bound to the DLK1 promoter and concomitantly caused dissociation of histone acetyltransferase p300 during adipogenesis.

conclusionsSE activation upregulates KLF6 through PPARγ/p300- and eRNA-mediated transcriptional induction during hADSC adipogenesis. KLF6, in turn, represses DLK1 expression through recruitment of HDAC3 to the promoter and p300 dissociation, thereby facilitating adipocyte differentiation. These findings support a working model in which the epigenetic regulation of KLF6 and DLK1 as a potential therapeutic axis in human obesity.

Indexed as

AdipogenesisADSCDLK1KLF6PPARγSuper-enhancer

Identifiers

PMID41549316
PMCPMC12829020

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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.