Evidence map›Paper›PMID 42706248›Full record

ArticleCell death & disease2026

The skin-specific long non-coding RNA TEDAR orchestrates late epidermal differentiation via an ERK-KLF4 cytoplasmic regulatory axis.

Kunal Das Mahapatra, Özge Arslan, Longlong Luo, Evelyn Kelemen, Sreeram Peringattu Kalarikkal, Lorenzo Pasquali, Christian Ziegler, Johannes Graf, Nicole Hemmer, Rachael Sugars and 3 more

Abstract read
In one paragraph

Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

13 authors.

Kunal Das Mahapatra *Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0002-2831-0751
Özge Arslan *Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0001-9515-494X
Longlong Luo *Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Evelyn KelemenDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Sreeram Peringattu KalarikkalDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Lorenzo PasqualiDepartment of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Christian ZieglerRegensburg Center for Biochemistry (RCB), University of Regensburg, Regensburg, Germany.
Johannes GrafRegensburg Center for Biochemistry (RCB), University of Regensburg, Regensburg, Germany.
Nicole HemmerDepartment of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Rachael SugarsDepartment of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.
Markus KretzInstitute for Molecular Medicine, MSH Medical School Hamburg, Hamburg, Germany.ORCID http://orcid.org/0000-0003-3420-3925
Eniko SonkolyDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Andor PivarcsiDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. andor.pivarcsi@imbim.uu.se.ORCID http://orcid.org/0000-0003-2196-1102

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The formation of a functional skin barrier depends on terminal keratinocyte differentiation, yet the contribution of long non-coding RNAs to this process remains incompletely understood. Here, using transcriptome analysis of more than 15,000 RNA-seq samples across 54 human tissues, we identify TEDAR (Terminal Epidermal Differentiation-Associated RNA), a highly skin-enriched lncRNA. Single-molecule RNA in situ hybridization revealed that TEDAR is confined to the uppermost granular layer of the epidermis, representing an exceptionally spatially restricted expression pattern. Functional studies demonstrated that CRISPR-mediated activation of TEDAR promotes keratinocyte differentiation even in the absence of external cues, while its depletion impaired late epidermal differentiation. In three-dimensional skin equivalents, TEDAR depletion severely compromises stratum corneum formation, highlighting its importance for proper epidermal barrier assembly. Mechanistically, TEDAR associates with ERK1/2-containing complexes and restrains ERK phosphorylation, thereby facilitating the nuclear accumulation of KLF4, a key regulator of epidermal differentiation. KLF4 depletion attenuated TEDAR-induced expression of several late differentiation genes, supporting a functional TEDAR-ERK-KLF4 axis. Clinically, TEDAR expression was reduced in cutaneous squamous cell carcinoma (cSCC) and chronic inflammatory skin diseases, including psoriasis and atopic dermatitis. Moreover, IL-22 suppressed TEDAR via STAT3 signalling in epidermal models. These findings identify TEDAR as an important regulator of terminal epidermal differentiation and suggest that its suppression may contribute to disturbed differentiation in inflammatory and neoplastic skin diseases.

Indexed as

Cell DifferentiationCytoplasmEpidermisKruppel-Like Transcription FactorsRNA, Long NoncodingSkinAnimalsHumansKeratinocytesKruppel-Like Factor 4KLF4 protein, humanKruppel-Like Factor 4Kruppel-Like Transcription FactorsRNA, Long Noncoding

Identifiers

PMID42706248
PMCPMC13550425

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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.