Evidence map›Paper›PMID 41534523›Full record

ArticleCell stem cell2026

Activation of a branched-chain amino acid rheostat restores replication-dependent hematopoietic stem cell fitness.

James Bartram, Sydney Treichel, Baobao Annie Song, Juying Xu, Devyani Sharma, Waseem Nasr, Madeline Frangiosa, Andrew Harley, Travis Nemkov, Angelo D'Alessandro and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Hematopoietic Stem Cell Metabolism during Stress and Aging.Advances in geriatric medicine and research · 2026
    Article
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

13 authors.

James BartramDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Cancer and Cell Biology graduate program, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Sydney TreichelDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Molecular and Developmental Biology Graduate Program, Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Baobao Annie SongDivision of Immunobiology and Center for Systems Immunology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH, USA; Immunobiology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Juying XuDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Devyani SharmaDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Cancer and Cell Biology graduate program, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Waseem NasrDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Madeline FrangiosaDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Andrew HarleyDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Travis NemkovDepartment of Biochemistry and Molecular Genetics, University of Colorado CU Anschutz Medical Campus, Aurora, CO, USA.
Angelo D'AlessandroDepartment of Biochemistry and Molecular Genetics, University of Colorado CU Anschutz Medical Campus, Aurora, CO, USA.
Nathan SalomonisDivision of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH, USA.
H Leighton GrimesDivision of Immunobiology and Center for Systems Immunology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH, USA.
Marie-Dominique FilippiDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address: marie-dominique.filippi@cchmc.org.

Funding

National Metabolomics Data Repository - nextgen Metabolomics WorkbenchU2CDK119886 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUBRAMANIAM, SHANKAR · 2018 to 2021
$12.7M
Mechanisms of granulocyte homeostasisR01HL122661 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI H. LEIGHTON GRIMES, Nathan G. Salomonis · 2015 to 2026
$5.3M
A generalizable framework for linking single-cell genomic states with cell fate outcomes in hematopoiesisRC2DK122376 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI GRIMES, H. LEIGHTON · 2020 to 2024
$5.3M
Biomedical Data Commons Workbench (BDCW)OT2OD030544 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUBRAMANIAM, SHANKAR · 2020 to 2024
$3.2M
The role of mitochondria in hematopoietic stem cell self-renewalR01HL151654 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI FILIPPI, MARIE-DOMINIQUE · 2021 to 2024
$2.4M
Regulation of functionally discrete hematopietic stem cellsR01DK121062 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI FILIPPI, MARIE-DOMINIQUE, GRIMES, H. LEIGHTON · 2020 to 2023
$2.3M
Regulatory mechanisms of hematopoietic stem cell functions post-transplantR01HL167731 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI Marie-Dominique Filippi · 2024 to 2026
$2.0M
NHLBI NIH HHS R01 HL122661NHLBI NIH HHS R01 HL151654NHLBI NIH HHS R01 HL167731NIDDK NIH HHS R01 DK121062NIDDK NIH HHS RC2 DK122376NIDDK NIH HHS U2C DK119886NIH HHS OT2 OD030544
6 · The paper itself

Abstract

Adult hematopoietic stem cells (HSCs) sustain the lifelong production of all mature blood and immune cells. HSCs possess extensive regenerative potential, but their self-renewal is limited. A long-standing question has been why replicative history negatively impacts HSC functions. We found that accrued divisions alter HSC production, generating low-output bone-marrow landscapes that are highly variable in lineage contribution and transcriptionally divergent within individual lineages. Division-driven HSC functional alterations arise from redirecting branched-chain amino acid (BCAA) usage from catabolic toward anabolic activity, causing faster HSC cell-cycle kinetics. Adding a BCAA transamination product overcomes the BCAA catabolic checkpoint and slows down the cell cycle, durably rescuing balanced lineage output of HSCs with accrued divisions. Hence, our study suggests the paradigm whereby replicative history causes metabolic and transcriptional drift, generating divergent HSC output. Division-dependent HSC functional drift can be restored by metabolite replacement, which has long-term therapeutic implications for HSC regenerative medicine.

Indexed as

Amino Acids, Branched-ChainHematopoietic Stem CellsAnimalsCell CycleCell DivisionCell LineageCell ProliferationMiceAmino Acids, Branched-Chainbranch chain amino acid catabolismhematopoietic stem cellsmetabolismself-renewal

Identifiers

PMID41534523
PMCPMC13122839

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.