Evidence map›Paper›PMID 34388375›Full record

ArticleCell stem cell2021

Hsf1 promotes hematopoietic stem cell fitness and proteostasis in response to ex vivo culture stress and aging.

Miriama Kruta, Mary Jean Sunshine, Bernadette A Chua, Yunpeng Fu, Ashu Chawla, Christopher H Dillingham, Lorena Hidalgo San Jose, Bijou De Jong, Fanny J Zhou, Robert A J Signer

Open access · hybridAbstract read
In one paragraph

Article in Cell stem cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 1 pooled it
5.8field-weighted citation impact, top 2% of its field
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

64 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. More than the 'master regulator of cytosolic proteostasis': new roles for HSF1 in promoting tissue health.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Science advances · 2025
    Article
  12. Article
  13. Centimeter-Scale Self-Assembling Tendon Organoids Drive Tissue Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  14. Article
  15. Review
  16. Article
  17. Metabolic regulation in the senescence process of stem cells.Stem cells translational medicine · 2025
    Review
  18. mRNA translational control of regeneration.Current opinion in genetics & development · 2025
    Review
  19. Review
  20. Article

4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Miriama KrutaDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Mary Jean SunshineDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Bernadette A ChuaDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Yunpeng FuDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Ashu ChawlaLa Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Christopher H DillinghamDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA; La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Lorena Hidalgo San JoseDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Bijou De JongDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Fanny J ZhouDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Robert A J SignerDivision of Regenerative Medicine, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: rsigner@ucsd.edu.
University of California San Diego · USLa Jolla Institute for Immunology · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesse Nodora · 1985 to 2026
$124.9M
Protein Homeostasis in Hematopoietic Stem CellsR01DK116951 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SIGNER, ROBERT A.J. · 2018 to 2025
$2.5M
Ex vivo hematopoietic stem cell growth mediated by the heat shock responseR01DK124775 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SIGNER, ROBERT A.J. · 2020 to 2023
$2.0M
FACSAria II Cell SorterS10RR027366 · NCRR · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI CROFT, MICHAEL · 2011 to 2011
$514k
NCI NIH HHS P30 CA023100NCRR NIH HHS S10 RR027366NIDDK NIH HHS R01 DK116951NIDDK NIH HHS R01 DK124775
6 · The paper itself

Abstract

Maintaining proteostasis is key to resisting stress and promoting healthy aging. Proteostasis is necessary to preserve stem cell function, but little is known about the mechanisms that regulate proteostasis during stress in stem cells, and whether disruptions of proteostasis contribute to stem cell aging is largely unexplored. We determined that ex-vivo-cultured mouse and human hematopoietic stem cells (HSCs) rapidly increase protein synthesis. This challenge to HSC proteostasis was associated with nuclear accumulation of Hsf1, and deletion of Hsf1 impaired HSC maintenance ex vivo. Strikingly, supplementing cultures with small molecules that enhance Hsf1 activation partially suppressed protein synthesis, rebalanced proteostasis, and supported retention of HSC serial reconstituting activity. Although Hsf1 was dispensable for young adult HSCs in vivo, Hsf1 deficiency increased protein synthesis and impaired the reconstituting activity of middle-aged HSCs. Hsf1 thus promotes proteostasis and the regenerative activity of HSCs in response to culture stress and aging.

Indexed as

Hematopoietic Stem CellsProteostasisAgingAnimalsCellular SenescenceMiceTranscription FactorsTranscription Factorsagingheat shock responsehematopoiesishematopoietic stem cellHsf1protein synthesisproteostasisstem cellstresstranslation

Identifiers

PMID34388375
PMCPMC8571035
OpenAlexW3191440760

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.