Evidence map›Paper›PMID 40898609›Full record

ArticleDevelopment, growth & differentiation2025

Super-Enhancer-Mediated DLX5 Activation Defines Regulatory Mechanisms in Human Embryonic Stem Cell-Derived Osteoblasts.

Shinse Fujita, Shoichiro Tani, Hiroyuki Okada, Taku Saito, Sakae Tanaka, Shinsuke Ohba, Ung-Il Chung, Hironori Hojo

Abstract read
In one paragraph

Article in Development, growth & differentiation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

8 authors.

Shinse FujitaDivision of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.ORCID https://orcid.org/0009-0009-4291-826X
Shoichiro TaniChildren's Research Institute and the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Hiroyuki OkadaDivision of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Taku SaitoDepartment of Orthopaedic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Sakae TanakaDepartment of Orthopaedic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Shinsuke OhbaDepartment of Tissue and Developmental Biology, Graduate School of Dentistry, The University of Osaka, Osaka, Japan.
Ung-Il ChungDivision of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Hironori HojoDivision of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0003-2245-6853

Funding

Daiichi Sankyo Foundation of Life ScienceJapan Agency for Medical Research and Development JP21bm0704071Japan Science and Technology Agency JPMJFR225NJapan Society for the Promotion of Science 23K21494Japan Society for the Promotion of Science 24KJ0606Japan Society for the Promotion of Science 25H01212Japan Society for the Promotion of Science 25K03449Nakatomi FoundationTerumo Foundation for Life Sciences and Arts
6 · The paper itself

Abstract

Osteoblast differentiation is essential for skeletal development and homeostasis. Although bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) are commonly used to study osteoblast differentiation in the context of bone homeostasis, their relevance to osteoblast differentiation during human skeletal development remains unclear. To understand the regulatory mechanisms underlying osteoblast differentiation in a human developmental context, we performed Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) and RNA-seq analyses on osteoblasts isolated from an in vivo implantation system using induced sclerotome derived from Col2.3-GFP reporter human embryonic stem cells (hESCs). The resulting datasets revealed skeletal development-associated chromatin accessibility and transcriptional profiles. Comparative analysis with BM-MSC-derived osteoblasts revealed that hESC-derived osteoblasts were enriched for regulatory gene sets associated with ossification. Notably, we identified a super-enhancer associated with DLX5, a known osteoblast regulator, consisting of multiple cooperative enhancer elements to drive transcription. Taken together, this study provides a valuable resource for examining cis-trans regulatory mechanisms in human skeletal development and highlights DLX5 as a key transcriptional regulator controlled by an osteoblast super-enhancer.

Indexed as

Enhancer Elements, GeneticHomeodomain ProteinsHuman Embryonic Stem CellsOsteoblastsCell DifferentiationHumansOsteogenesisTranscription FactorsDLX5 protein, humanHomeodomain ProteinsTranscription Factors

Identifiers

PMID40898609
PMCPMC12477830

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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.