Evidence map›Paper›PMID 34715054›Full record

ArticleStem cell reports2021

CITED2 coordinates key hematopoietic regulatory pathways to maintain the HSC pool in both steady-state hematopoiesis and transplantation.

Hannah Lawson, Louie N van de Lagemaat, Melania Barile, Andrea Tavosanis, Jozef Durko, Arnaud Villacreces, Aarushi Bellani, Christopher Mapperley, Elise Georges, Catarina Martins-Costa and 10 more

Open access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

12 citing papers in PubMed, 19 citations in OpenAlex.

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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

20 authors at 8 institutions in 3 countries.

Hannah LawsonLaboratory of Haematopoietic Stem Cell & Leukaemia Biology, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK; Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Louie N van de LagemaatLaboratory of Haematopoietic Stem Cell & Leukaemia Biology, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK; Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Melania BarileDepartment of Haematology, Wellcome and Medical Research Council Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AW, UK.
Andrea TavosanisLaboratory of Haematopoietic Stem Cell & Leukaemia Biology, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK.
Jozef DurkoLaboratory of Haematopoietic Stem Cell & Leukaemia Biology, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK.
Arnaud VillacrecesCentre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Aarushi BellaniLaboratory of Haematopoietic Stem Cell & Leukaemia Biology, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK.
Christopher MapperleyLaboratory of Haematopoietic Stem Cell & Leukaemia Biology, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK.
Elise GeorgesLaboratory of Haematopoietic Stem Cell & Leukaemia Biology, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK.
Catarina Martins-CostaCentre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Catarina SepulvedaCentre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Lewis AllenLaboratory of Haematopoietic Stem Cell & Leukaemia Biology, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK.
Joana CamposLaboratory of Haematopoietic Stem Cell & Leukaemia Biology, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK.
Kirsteen J CampbellCRUK Beatson Institute, Glasgow, UK.
Dónal O'CarrollCentre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
Berthold GöttgensDepartment of Haematology, Wellcome and Medical Research Council Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0AW, UK.
Suzanne CoryThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Neil P RodriguesEuropean Cancer Stem Cell Research Institute, Cardiff University, School of Biosciences, Cardiff CF24 4HQ, UK.
Amelie V GuitartCentre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK; Université de Bordeaux, Institut National de la Santé et de la Recherche Médicale INSERM U1035, 33000 Bordeaux, France. Electronic address: amelie.guitart@u-bordeaux.fr.
Kamil R KrancLaboratory of Haematopoietic Stem Cell & Leukaemia Biology, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK. Electronic address: kamil.kranc@qmul.ac.uk.
Queen Mary University of London · GBMRC Centre for Regenerative Medicine · GBUniversity of Edinburgh · GBCancer Research UK Scotland Institute · GBCardiff University · GBMedical Research Council · GBWalter and Eliza Hall Institute of Medical Research · AUWellcome/MRC Cambridge Stem Cell Institute · GB

Funding

Cancer Research UK 14633Cancer Research UK 26787Cancer Research UK C29967/A14633Cancer Research UK C29967/A26787Medical Research Council MC_PC_17230Medical Research Council MR/P010008/1Medical Research Council MR/P010008/2Wellcome TrustWellcome Trust 203151/Z/16/Z
6 · The paper itself

Abstract

Hematopoietic stem cells (HSCs) reside at the apex of the hematopoietic differentiation hierarchy and sustain multilineage hematopoiesis. Here, we show that the transcriptional regulator CITED2 is essential for life-long HSC maintenance. While hematopoietic-specific Cited2 deletion has a minor impact on steady-state hematopoiesis, Cited2-deficient HSCs are severely depleted in young mice and fail to expand upon aging. Moreover, although they home normally to the bone marrow, they fail to reconstitute hematopoiesis upon transplantation. Mechanistically, CITED2 is required for expression of key HSC regulators, including GATA2, MCL-1, and PTEN. Hematopoietic-specific expression of anti-apoptotic MCL-1 partially rescues the Cited2-deficient HSC pool and restores their reconstitution potential. To interrogate the Cited2→Pten pathway in HSCs, we generated Cited2;Pten compound heterozygous mice, which had a decreased number of HSCs that failed to reconstitute the HSC compartment. In addition, CITED2 represses multiple pathways whose elevated activity causes HSC exhaustion. Thus, CITED2 promotes pathways necessary for HSC maintenance and suppresses those detrimental to HSC integrity.

Indexed as

Gene Expression RegulationAnimalsApoptosisCell ProliferationGene Regulatory NetworksHematopoiesisHematopoietic Stem CellsHematopoietic Stem Cell TransplantationMiceMice, Inbred C57BLMice, KnockoutRepressor ProteinsReverse Transcriptase Polymerase Chain ReactionRNA-SeqSignal TransductionTime FactorsCited2 protein, mouseRepressor ProteinsTrans-ActivatorsCITED2hematopoiesishematopoietic stem cellMCL-1PTEN

Identifiers

PMID34715054
PMCPMC8581166
OpenAlexW3211060478

What OpenQuestion holds

Textmetadata
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.