Evidence map›Paper›PMID 33444287›Full record

ArticleThe Journal of clinical investigation2021

Concerted roles of PTEN and ATM in controlling hematopoietic stem cell fitness and dormancy.

Jerome Fortin, Christian Bassi, Parameswaran Ramachandran, Wanda Y Li, Ruxiao Tian, Ida Zarrabi, Graham Hill, Bryan E Snow, Jillian Haight, Chantal Tobin and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

9 citing papers in PubMed, 14 citations in OpenAlex.

  1. NIBAN2/FLII/RREB1 Axis Drives Glioma Stem Cell Malignancy via TLR3 Pathway Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Clonal hematopoiesis and bone marrow inflammation.Translational research : the journal of laboratory and clinical medicine · 2023
    Review
  8. Molecular regulation of hematopoietic stem cell quiescence.Cellular and molecular life sciences : CMLS · 2022
    Review
  9. Cell and Gene Therapy for Anemia: Hematopoietic Stem Cells and Gene Editing.International journal of molecular sciences · 2021
    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

14 authors at 1 institution in 1 country.

Jerome FortinPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Christian BassiPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Parameswaran RamachandranPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Wanda Y LiPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Ruxiao TianPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Ida ZarrabiPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Graham HillPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Bryan E SnowPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Jillian HaightPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Chantal TobinPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Kelsey HodgsonPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Andrew WakehamPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Vuk StambolicPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Tak W MakPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
University Health Network · CA

Funding

CIHR
6 · The paper itself

Abstract

In order to sustain proficient life-long hematopoiesis, hematopoietic stem cells (HSCs) must possess robust mechanisms to preserve their quiescence and genome integrity. DNA-damaging stress can perturb HSC homeostasis by affecting their survival, self-renewal, and differentiation. Ablation of the kinase ataxia telangiectasia mutated (ATM), a master regulator of the DNA damage response, impairs HSC fitness. Paradoxically, we show here that loss of a single allele of Atm enhances HSC functionality in mice. To explain this observation, we explored a possible link between ATM and the tumor suppressor phosphatase and tensin homolog (PTEN), which also regulates HSC function. We generated and analyzed a knockin mouse line (PtenS398A/S398A), in which PTEN cannot be phosphorylated by ATM. Similar to Atm+/-, PtenS398A/S398A HSCs have enhanced hematopoietic reconstitution ability, accompanied by resistance to apoptosis induced by genotoxic stress. Single-cell transcriptomic analyses and functional assays revealed that dormant PtenS398A/S398A HSCs aberrantly tolerate elevated mitochondrial activity and the accumulation of reactive oxygen species, which are normally associated with HSC priming for self-renewal or differentiation. Our results unveil a molecular connection between ATM and PTEN, which couples the response to genotoxic stress and dormancy in HSCs.

Indexed as

ApoptosisCell DifferentiationDNA DamageAmino Acid SubstitutionAnimalsAtaxia Telangiectasia Mutated ProteinsHematopoietic Stem CellsMiceMice, TransgenicMutation, MissensePTEN PhosphohydrolaseAtaxia Telangiectasia Mutated ProteinsAtm protein, mousePTEN PhosphohydrolasePten protein, mouseDNA repairHematologyHematopoietic stem cellsStem cells

Identifiers

PMID33444287
PMCPMC7919727
OpenAlexW3118686664

What OpenQuestion holds

Textmetadata
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.