Evidence map›Paper›PMID 40513561›Full record

ArticleCell metabolism2025

The integrated stress response fine-tunes stem cell fate decisions upon serine deprivation and tissue injury.

Jesse S S Novak, Lisa Polak, Sanjeethan C Baksh, Douglas W Barrows, Marina Schernthanner, Benjamin T Jackson, Elizabeth A N Thompson, Anita Gola, M Deniz Abdusselamoglu, Alain R Bonny and 12 more

Abstract read
In one paragraph

Article in Cell metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. The Yin-Yang of Stress and Senescence: Integrated Stress Response and SASP Crosstalk in Stem Cell Fate, Regeneration, and Disease.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2026
    Article
  5. Article
  6. Review
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

22 authors.

Jesse S S NovakRobin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Lisa PolakRobin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Sanjeethan C BakshRobin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Douglas W BarrowsBioinformatics Resource Center, The Rockefeller University, New York, NY 10065, USA.
Marina SchernthannerRobin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Benjamin T JacksonCell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Elizabeth A N ThompsonRobin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Anita GolaRobin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
M Deniz AbdusselamogluRobin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Alain R BonnyRobin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Kevin A U GonzalesRobin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Julia S BrunnerCell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Anna E BridgemanCell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Katie S StewartRobin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Lynette HidalgoRobin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
June Dela Cruz-RacelisRobin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Ji-Dung LuoBioinformatics Resource Center, The Rockefeller University, New York, NY 10065, USA.
Shiri Gur-CohenRobin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
H Amalia PasolliElectron Microscopy Resource Center, The Rockefeller University, New York, NY 10065, USA.
Thomas S CarrollBioinformatics Resource Center, The Rockefeller University, New York, NY 10065, USA.
Lydia W S FinleyCell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Elaine FuchsRobin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA. Electronic address: fuchslb@rockefeller.edu.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Weill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1M
VITAMIN A AND KERATINIZATION IN HUMAN EPITHELIAL CELLSR01AR031737 · NIAMS · UNIVERSITY OF CHICAGO · PI ELAINE FUCHS · 1986 to 2026
$16.6M
GENE EXPRESSION AND DIFFERENTIATION IN HUMAN EPIDERMISR37AR027883 · NIAMS · UNIVERSITY OF CHICAGO · PI ELAINE FUCHS · 1994 to 2026
$13.3M
Skin Stem Cells: Purification and CharacterizationR01AR050452 · NIAMS · ROCKEFELLER UNIVERSITY · PI ELAINE FUCHS · 2004 to 2026
$8.6M
GENE EXPRESSION &DIFFERENTIATION IN HUMAN EPIDERMISR01AR027883 · NIAMS · UNIVERSITY OF CHICAGO · PI FUCHS, ELAINE · 1986 to 2022
$7.6M
Weill Cornell/Rockefeller/Sloan Kettering MST ProgramT32GM152349 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI KATHARINE C HSU · 2024 to 2026
$6.6M
Dissecting the role of serine metabolism in stem cell fate and tissue regenerationF30HD107964 · NICHD · WEILL MEDICAL COLL OF CORNELL UNIV · PI NOVAK, JESSE STEPHEN SWYER · 2021 to 2025
$211k
Metabolic control of exit from naïve pluripotencyF30HD107943 · NICHD · WEILL MEDICAL COLL OF CORNELL UNIV · PI JACKSON, BENJAMIN TONNU · 2022 to 2025
$184k
NCI NIH HHS P30 CA008748NIAMS NIH HHS R01 AR027883NIAMS NIH HHS R01 AR031737NIAMS NIH HHS R01 AR050452NIAMS NIH HHS R37 AR027883NICHD NIH HHS F30 HD107943NICHD NIH HHS F30 HD107964NIGMS NIH HHS T32 GM007739NIGMS NIH HHS T32 GM152349
6 · The paper itself

Abstract

Epidermal stem cells produce the skin's barrier that excludes pathogens and prevents dehydration. Hair follicle stem cells (HFSCs) are dedicated to bursts of hair regeneration, but upon injury, they can also reconstruct, and thereafter maintain, the overlying epidermis. How HFSCs balance these fate choices to restore physiologic function to damaged tissue remains poorly understood. Here, we uncover serine as an unconventional, non-essential amino acid that impacts this process. When dietary serine dips, endogenous biosynthesis in HFSCs fails to meet demands (and vice versa), slowing hair cycle entry. Serine deprivation also alters wound repair, further delaying hair regeneration while accelerating re-epithelialization kinetics. Mechanistically, we show that HFSCs sense each fitness challenge by triggering the integrated stress response, which acts as a rheostat of epidermal-HF identity. As stress levels rise, skin barrier restoration kinetics accelerate while hair growth is delayed. Our findings offer potential for dietary and pharmacological intervention to accelerate wound healing.

Indexed as

Hair FollicleSerineStem CellsStress, PhysiologicalAnimalsCell DifferentiationMaleMiceMice, Inbred C57BLRegenerationSkinWound HealingSerinedietary interventionepidermal stem cellsfate selectionhair follicle stem cellshair regrowthintegrated stress responseserine metabolismtissue regenerationtissue repairwound healing

Identifiers

PMID40513561
PMCPMC12210826

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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.