Evidence map›Paper›PMID 27918563›Full record

ArticleNature medicine2017

Dickkopf-1 promotes hematopoietic regeneration via direct and niche-mediated mechanisms.

Heather A Himburg, Phuong L Doan, Mamle Quarmyne, Xiao Yan, Joshua Sasine, Liman Zhao, Grace V Hancock, Jenny Kan, Katherine A Pohl, Evelyn Tran and 3 more

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

Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% 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

58 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Diallyl disulfide reduces oxidative stress to mitigate uranium tailings radiation-induced damage to the hematopoietic system.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026
    Article
  5. Article
  6. Review
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  8. Bone marrow adipocytes: key players in vascular niches, aging, and disease.Frontiers in cell and developmental biology · 2025
    Review
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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

13 authors at 2 institutions in 1 country.

Heather A HimburgDivision of Hematology and Oncology, Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California, USA.
Phuong L DoanDivision of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, North Carolina, USA.
Mamle QuarmyneDivision of Hematology and Oncology, Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California, USA.
Xiao YanDivision of Hematology and Oncology, Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California, USA.
Joshua SasineDivision of Hematology and Oncology, Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California, USA.
Liman ZhaoDivision of Hematology and Oncology, Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California, USA.
Grace V HancockDepartment of Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California, USA.
Jenny KanDivision of Hematology and Oncology, Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California, USA.
Katherine A PohlDivision of Hematology and Oncology, Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California, USA.
Evelyn TranDivision of Hematology and Oncology, Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California, USA.
Nelson J ChaoDivision of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, North Carolina, USA.
Jeffrey R HarrisDivision of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, North Carolina, USA.
John P ChuteDivision of Hematology and Oncology, Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California, USA.
University of California, Los Angeles · USDuke University · US

Funding

Sample Engineering CoreU19AI067773 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI FORNACE, ALBERT J · 2005 to 2024
$105.4M
Somatostatin analogues as countermeasures against intestinal radiation toxicityU19AI067798 · NIAID · DUKE UNIVERSITY · PI CHAO, NELSON J. · 2005 to 2024
$82.1M
UCLA Center for Biological RadioprotectorsU19AI067769 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MCBRIDE, WILLIAM H. · 2005 to 2019
$44.6M
Semaphorin signaling regulates vascular and hematopoietic regenerationR01HL086998 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHUTE, JOHN P · 2008 to 2022
$4.6M
Epidermal growth factor mitigates radiation-induced hematopoietic failureU01AI107333 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHUTE, JOHN P · 2013 to 2017
$2.6M
Role of ErbB receptor signaling in regulating normal and leukemic stem cell fateK08CA184552 · NCI · DUKE UNIVERSITY · PI DOAN, PHUONG LINH · 2014 to 2018
$639k
NCI NIH HHS K08 CA184552NHLBI NIH HHS R01 HL086998NIAID NIH HHS U01 AI107333NIAID NIH HHS U19 AI067769NIAID NIH HHS U19 AI067773NIAID NIH HHS U19 AI067798
6 · The paper itself

Abstract

The role of osteolineage cells in regulating hematopoietic stem cell (HSC) regeneration following myelosuppression is not well understood. Here we show that deletion of the pro-apoptotic genes Bak and Bax in osterix (Osx, also known as Sp7 transcription factor 7)-expressing cells in mice promotes HSC regeneration and hematopoietic radioprotection following total body irradiation. These mice showed increased bone marrow (BM) levels of the protein dickkopf-1 (Dkk1), which was produced in Osx-expressing BM cells. Treatment of irradiated HSCs with Dkk1 in vitro increased the recovery of both long-term repopulating HSCs and progenitor cells, and systemic administration of Dkk1 to irradiated mice increased hematopoietic recovery and improved survival. Conversely, inducible deletion of one allele of Dkk1 in Osx-expressing cells in adult mice inhibited the recovery of BM stem and progenitor cells and of complete blood counts following irradiation. Dkk1 promoted hematopoietic regeneration via both direct effects on HSCs, in which treatment with Dkk1 decreased the levels of mitochondrial reactive oxygen species and suppressed senescence, and indirect effects on BM endothelial cells, in which treatment with Dkk1 induced epidermal growth factor (EGF) secretion. Accordingly, blockade of the EGF receptor partially abrogated Dkk1-mediated hematopoietic recovery. These data identify Dkk1 as a regulator of hematopoietic regeneration and demonstrate paracrine cross-talk between BM osteolineage cells and endothelial cells in regulating hematopoietic reconstitution following injury.

Indexed as

Cell Self RenewalRegenerationWhole-Body IrradiationAnimalsbcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinBone MarrowBone Marrow CellsCytokinesEndothelial CellsEnzyme-Linked Immunosorbent AssayEpidermal Growth FactorErbB ReceptorsFlow CytometryGene Expression ProfilingHematopoietic Stem CellsBak1 protein, mouseBax protein, mousebcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinCytokinesDkk1 protein, mouseEpidermal Growth FactorErbB ReceptorsIntercellular Signaling Peptides and ProteinsReactive Oxygen SpeciesSp7 protein, mouseSp7 Transcription FactorTranscription Factors

Identifiers

PMID27918563
PMCPMC5592969
OpenAlexW2560632721

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.