Evidence map›Paper›PMID 41265446›Full record

ArticleCell genomics2026

Genetic architecture of the murine red blood cell proteome reveals central role of hemoglobin beta cysteine 93 in maintaining redox balance.

Gregory R Keele, Monika Dzieciatkowska, Ariel M Hay, Matthew Vincent, Callan O'Connor, Daniel Stephenson, Julie A Reisz, Travis Nemkov, Kirk C Hansen, Grier P Page and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell genomics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Fifteen years of the Diversity Outbred mouse model: a review.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Gregory R KeeleRTI International, Research Triangle Park, NC, USA; The Jackson Laboratory, Bar Harbor, ME 04609, USA.
Monika DzieciatkowskaDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, USA.
Ariel M HayUniversity of Virginia, Charlottesville, VA, USA.
Matthew VincentRTI International, Research Triangle Park, NC, USA.
Callan O'ConnorRTI International, Research Triangle Park, NC, USA.
Daniel StephensonDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, USA.
Julie A ReiszDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, USA.
Travis NemkovDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, USA; Omix Technologies, Inc., Aurora, CO, USA.
Kirk C HansenDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, USA; Omix Technologies, Inc., Aurora, CO, USA.
Grier P PageRTI International, Research Triangle Park, NC, USA.
James C ZimringUniversity of Virginia, Charlottesville, VA, USA; University of British Columbia, Vancouver, BC, Canada; Canadian Blood Services, Vancouver, BC, Canada. Electronic address: jcz2k@viriginia.edu.
Gary A ChurchillThe Jackson Laboratory, Bar Harbor, ME 04609, USA. Electronic address: gary.churchill@jax.org.
Angelo D'AlessandroDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, USA; Omix Technologies, Inc., Aurora, CO, USA. Electronic address: angelo.dalessandro@cuanschutz.edu.

Funding

The role of ferroptosis in red cell aging in vivo and in vitroR01HL146442 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI Angelo D'Alessandro, Adam N. Goldfarb · 2019 to 2026
$5.4M
NHLBI NIH HHS R01 HL146442
6 · The paper itself

Abstract

Red blood cells (RBCs) transport oxygen but accumulate oxidative damage over time, reducing function in vivo and during storage, critical for transfusions. To explore the genetics of RBC resilience, we profiled proteins, metabolites, and lipids from fresh and stored RBCs from 350 genetically diverse mice. Our analysis identified over 6,000 quantitative trait loci (QTLs). Compared to other tissues, the prevalence of trans genetic effects over cis ones reflects the absence of de novo protein synthesis in anucleated RBCs. QTL hotspots at Hbb, Hba, Mon1a, and (storage-specific) Steap3 linked ferroptosis to hemolysis. Proteasome QTLs clustered at multiple loci, underscoring the importance of degrading oxidized proteins. Post-translational modification (PTM) QTLs mapped predominantly to hemoglobins, including cysteine residues. The loss of reactive C93 in humanized mice (hemoglobulin beta [HBB] C93A) disrupted redox balance, glutathione pools, glutathionylation, and redox PTMs. These findings highlight genetic regulation of RBC oxidation, with implications for transfusion biology and oxidative-stress-dependent hemolytic disorders.

Indexed as

CysteineErythrocytesHemoglobinsProteomeAnimalsGlutathioneHemolysisHumansMaleMiceMice, Inbred C57BLOxidation-ReductionOxidative StressProtein Processing, Post-TranslationalQuantitative Trait LociCysteineGlutathioneHemoglobinsProteomeblood transfusionDiversity Outbred miceerythrocytehematologyhemoglobinoxidative stresspQTLPTM QTLstorage lesion

Identifiers

PMID41265446
PMCPMC12985394

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.