Evidence map›Paper›PMID 42768052›Full record

ArticleNature communications2026

Fatty acid oxidation fuels mitochondrial respiration to drive epidermal stem cell fate and differentiation.

Kristina Todorova, Stefano Sol, Fabiana Boncimino, Andrea Clocchiatti, Kazuki Takagaki, Enkhtuul Gantumur, Mihaela Ruseva, Meaghan Cadieux, Michelle Liu, Victor A Neel and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 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
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Kristina Todorova *Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Stefano Sol *Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.ORCID http://orcid.org/0000-0003-2576-0156
Fabiana Boncimino *Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Andrea ClocchiattiCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Kazuki TakagakiCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.ORCID http://orcid.org/0000-0002-8153-8077
Enkhtuul GantumurCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.ORCID http://orcid.org/0000-0002-1549-6374
Mihaela RusevaCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Meaghan CadieuxCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Michelle LiuCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Victor A NeelDepartment of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Amy S ColwellDivision of Plastic and Reconstructive Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Christine G LianDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
George F MurphyDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Peter CarmelietLaboratory of Angiogenesis and Vascular Metabolism, University of Leuven, Leuven, Belgium.ORCID http://orcid.org/0000-0001-7961-1821
Anna MandinovaCutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA. amandinova@mgh.harvard.edu.ORCID http://orcid.org/0000-0001-9273-0972

Funding

Stem Cell Integral Membrane Transporter ABCB5 and Dermal RegenerationP01AG071463 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI Markus H. Frank · 2022 to 2026
$13.6M
NIA NIH HHS P01 AG071463U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) 1P01AG071463-02
6 · The paper itself

Abstract

Skin barrier function relies on the epidermis, whose integrity is maintained by basal stem cells that continuously renew and differentiate into a multilayered architecture. Disrupted epidermal differentiation underlies numerous hyperproliferative and inflammatory skin disorders. While transcriptional and epigenetic mechanisms are known to regulate late differentiation, the molecular events driving early commitment remain elusive. Here, we reveal that early mitochondrial reprogramming, characterized by the activation of oxidative phosphorylation, is a determinant of differentiation initiation. We identify fatty acid oxidation as the primary metabolic pathway fueling oxidative phosphorylation during this process. Pharmacological and genetic inhibition of fatty acid oxidation, in vitro and in vivo, disrupts differentiation and compromises stratification, causing defective responses to physical insults. Mechanistically, fatty acid oxidation enables ATP production in committed epidermal cells to support the differentiation process, linking lipid metabolism and epidermal homeostasis. These results uncover an unrecognized role for metabolic reprogramming in epidermal stem cell fate and highlight fatty acid oxidation as a promising therapeutic target for restoring differentiation defects in disease.

Indexed as

Cell DifferentiationEpidermal CellsFatty AcidsMitochondriaStem CellsAdenosine TriphosphateAnimalsCell RespirationEpidermisHumansKeratinocytesLipid MetabolismMetabolic ReprogrammingMiceOxidation-ReductionOxidative PhosphorylationAdenosine TriphosphateFatty Acids

Identifiers

PMID42768052
PMCPMC13594288

What OpenQuestion holds

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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.