Evidence map›Paper›PMID 33758188›Full record

ArticleNature communications2021

Mutant ASXL1 induces age-related expansion of phenotypic hematopoietic stem cells through activation of Akt/mTOR pathway.

Takeshi Fujino, Susumu Goyama, Yuki Sugiura, Daichi Inoue, Shuhei Asada, Satoshi Yamasaki, Akiko Matsumoto, Kiyoshi Yamaguchi, Yumiko Isobe, Akiho Tsuchiya and 15 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
10.5field-weighted citation impact, top 1% 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

76 citing papers in PubMed, 92 citations in OpenAlex.

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  5. TruncatingbioRxiv : the preprint server for biology · 2026
    Article
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  9. Hematopoietic Aging and Leukemia: Mechanistic and Therapeutic Insights.International journal of molecular sciences · 2026
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16 more citing papers are in PubMed but not listed here.

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

25 authors at 5 institutions in 2 countries.

Takeshi FujinoDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Susumu GoyamaDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Yuki SugiuraDepartment of Biochemistry, Keio University School of Medicine, and Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO), Suematsu Gas Biology Project, Shinjuku-ku, Tokyo, Japan.
Daichi InoueHuman Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, USA.
Shuhei AsadaDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.ORCID http://orcid.org/0000-0001-6116-7996
Satoshi YamasakiLaboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Akiko MatsumotoLaboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Kiyoshi YamaguchiDivision of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Yumiko IsobeDivision of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Akiho TsuchiyaDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Shiori ShikataDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Naru SatoDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Hironobu MorinagaDepartment of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Tomofusa FukuyamaDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.ORCID http://orcid.org/0000-0002-0709-3188
Yosuke TanakaDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Tsuyoshi FukushimaDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Reina TakedaDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Keita YamamotoDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Hiroaki HondaField of Human Disease Models, Major in Advanced Life Sciences and Medicine, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
Emi K NishimuraDepartment of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.ORCID http://orcid.org/0000-0002-5767-8045
Yoichi FurukawaDivision of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Tatsuhiro ShibataLaboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Omar Abdel-WahabHuman Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, USA.ORCID http://orcid.org/0000-0002-3907-6171
Makoto SuematsuDepartment of Biochemistry, Keio University School of Medicine, and Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO), Suematsu Gas Biology Project, Shinjuku-ku, Tokyo, Japan.ORCID http://orcid.org/0000-0002-7165-6336
Toshio KitamuraDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan. kitamura@ims.u-tokyo.ac.jp.ORCID http://orcid.org/0000-0001-7855-1767
The University of Tokyo · JPKeio University · JPMemorial Sloan Kettering Cancer Center · USTokyo Medical and Dental University · JPTokyo Women's Medical University · JP

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Somatic mutations of ASXL1 are frequently detected in age-related clonal hematopoiesis (CH). However, how ASXL1 mutations drive CH remains elusive. Using knockin (KI) mice expressing a C-terminally truncated form of ASXL1-mutant (ASXL1-MT), we examined the influence of ASXL1-MT on physiological aging in hematopoietic stem cells (HSCs). HSCs expressing ASXL1-MT display competitive disadvantage after transplantation. Nevertheless, in genetic mosaic mouse model, they acquire clonal advantage during aging, recapitulating CH in humans. Mechanistically, ASXL1-MT cooperates with BAP1 to deubiquitinate and activate AKT. Overactive Akt/mTOR signaling induced by ASXL1-MT results in aberrant proliferation and dysfunction of HSCs associated with age-related accumulation of DNA damage. Treatment with an mTOR inhibitor rapamycin ameliorates aberrant expansion of the HSC compartment as well as dysregulated hematopoiesis in aged ASXL1-MT KI mice. Our findings suggest that ASXL1-MT provokes dysfunction of HSCs, whereas it confers clonal advantage on HSCs over time, leading to the development of CH.

Indexed as

AgedAgingAnimalsApoptosisCell CycleCell ProliferationCells, CulturedClonal HematopoiesisDNA DamageGene Knock-In TechniquesHematopoiesisHematopoietic Stem CellsHematopoietic Stem Cell TransplantationHumansMembrane Potential, MitochondrialMiceAsxl1 protein, mouseBAP1 protein, mouseProto-Oncogene Proteins c-aktReactive Oxygen SpeciesRepressor ProteinsSirolimusTOR Serine-Threonine KinasesTumor Suppressor ProteinsUbiquitin Thiolesterase

Identifiers

PMID33758188
PMCPMC7988019
OpenAlexW3138213655

What OpenQuestion holds

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LicenceCC BY
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.