Evidence map›Paper›PMID 34450065›Full record

ArticleCell stem cell2021

Aspartate availability limits hematopoietic stem cell function during hematopoietic regeneration.

Le Qi, Misty S Martin-Sandoval, Salma Merchant, Wen Gu, Matthias Eckhardt, Thomas P Mathews, Zhiyu Zhao, Michalis Agathocleous, Sean J Morrison

Open access · bronzeAbstract 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 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
8.8field-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

50 citing papers in PubMed, 78 citations in OpenAlex.

  1. Loss of TCA cycle turning promotes stem cell function.bioRxiv : the preprint server for biology · 2026
    Article
  2. Article
  3. Hematopoietic Stem Cell Metabolism during Stress and Aging.Advances in geriatric medicine and research · 2026
    Article
  4. Article
  5. Article
  6. GOT2-mediated suppression of CoQCommunications biology · 2026
    Article
  7. Article
  8. A Stable Isotope Tracing Primer for the Mass Spectrometrist.Annual review of analytical chemistry (Palo Alto, Calif.) · 2026
    Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Hematopoietic stem cell metabolism within the bone marrow niche - insights and opportunities.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  20. 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

9 authors at 2 institutions in 2 countries.

Le QiChildren's Research Institute and the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Misty S Martin-SandovalChildren's Research Institute and the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Salma MerchantChildren's Research Institute and the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Wen GuChildren's Research Institute and the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Matthias EckhardtInstitute of Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, Bonn, North Rhine-Westphalia 53115, Germany.
Thomas P MathewsChildren's Research Institute and the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Zhiyu ZhaoChildren's Research Institute and the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Michalis AgathocleousChildren's Research Institute and the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Sean J MorrisonChildren's Research Institute and the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: sean.morrison@utsouthwestern.edu.
The University of Texas Southwestern Medical Center · USUniversity of Bonn · DE

Funding

The Regulation of Stem Cell AgingR37AG024945 · NIA · UT SOUTHWESTERN MEDICAL CENTER · PI MORRISON, SEAN J · 2009 to 2018
$3.1M
The Metabolic Regulation of Hematopoietic Stem Cell FunctionR01DK118745 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI MORRISON, SEAN J · 2019 to 2023
$1.8M
REDUCING HIV RISK IN DRUG ABUSING YOUTHR01DA011875 · NIDA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI DEVIEUX, JESSY G · 1998 to 2004
$1.0M
Howard Hughes Medical InstituteNIA NIH HHS R37 AG024945NIDA NIH HHS R01 DA011875NIDDK NIH HHS R01 DK118745
6 · The paper itself

Abstract

The electron transport chain promotes aspartate synthesis, which is required for cancer cell proliferation. However, it is unclear whether aspartate is limiting in normal stem cells. We found that mouse hematopoietic stem cells (HSCs) depend entirely on cell-autonomous aspartate synthesis, which increases upon HSC activation. Overexpression of the glutamate/aspartate transporter, Glast, or deletion of glutamic-oxaloacetic transaminase 1 (Got1) each increased aspartate levels in HSCs/progenitor cells and increased the function of HSCs but not colony-forming progenitors. Conversely, deletion of Got2 reduced aspartate levels and the function of HSCs but not colony-forming progenitors. Deletion of Got1 and Got2 eliminated HSCs. Isotope tracing showed aspartate was used to synthesize asparagine and purines. Both contributed to increased HSC function as deletion of asparagine synthetase or treatment with 6-mercaptopurine attenuated the increased function of GLAST-overexpressing HSCs. HSC function is thus limited by aspartate, purine, and asparagine availability during hematopoietic regeneration.

Indexed as

Aspartic AcidHematopoietic Stem CellsAnimalsCell ProliferationMiceAspartic Acidasparagineaspartateelectron transport chainhematopoietic stem cellmetabolismmitochondriapurineregeneration

Identifiers

PMID34450065
PMCPMC8571029
OpenAlexW3194144433

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.