Evidence mapPaperPMID 38278152Full record

ArticleStem cell reports2024

Proinflammatory phenotype of iPS cell-derived JAK2 V617F megakaryocytes induces fibrosis in 3D in vitro bone marrow niche.

Niclas Flosdorf, Janik Böhnke, Marcelo A S de Toledo, Niklas Lutterbach, Vanesa Gómez Lerma, Martin Graßhoff, Kathrin Olschok, Siddharth Gupta, Vithurithra Tharmapalan, Susanne Schmitz and 14 more

Open access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
5.7field-weighted citation impact, top 4% 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

8 citing papers in PubMed, 13 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

24 authors at 4 institutions in 2 countries.

Niclas FlosdorfDepartment of Cell Biology, Institute for Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany; Institute for Cell and Tumor Biology, RWTH Aachen University Medical School, Aachen, Germany; Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany.
Janik BöhnkeDepartment of Cell Biology, Institute for Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany; Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany.
Marcelo A S de ToledoCenter for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University Hospital, Aachen, Germany.
Niklas LutterbachInstitute for Cell and Tumor Biology, RWTH Aachen University Medical School, Aachen, Germany.
Vanesa Gómez LermaDepartment of Cell Biology, Institute for Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.
Martin GraßhoffInstitute of Computational Genomics, RWTH Aachen University Hospital, Aachen, Germany.
Kathrin OlschokCenter for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University Hospital, Aachen, Germany.
Siddharth GuptaCenter for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University Hospital, Aachen, Germany.
Vithurithra TharmapalanHelmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany; Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany; Institute for Stem Cell Biology, RWTH Aachen University Medical School, Aachen, Germany.
Susanne SchmitzInstitute for Cell and Tumor Biology, RWTH Aachen University Medical School, Aachen, Germany.
Katrin GötzInstitute for Cell and Tumor Biology, RWTH Aachen University Medical School, Aachen, Germany.
Herdit M SchülerInstitute for Human Genetics and Genome Medicine, Faculty of Medicine, RWTH Aachen University, Aachen, Germany; Center for Rare Diseases, Medical Faculty, and University Hospital Düsseldorf Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Angela MaurerCenter for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University Hospital, Aachen, Germany.
Stephanie SontagDepartment of Cell Biology, Institute for Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.
Caroline KüstermannDepartment of Cell Biology, Institute for Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.
Kristin SeréDepartment of Cell Biology, Institute for Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany; Institute for Cell and Tumor Biology, RWTH Aachen University Medical School, Aachen, Germany.
Wolfgang WagnerHelmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany; Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany; Institute for Stem Cell Biology, RWTH Aachen University Medical School, Aachen, Germany.
Ivan G CostaInstitute of Computational Genomics, RWTH Aachen University Hospital, Aachen, Germany.
Tim H BrümmendorfCenter for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University Hospital, Aachen, Germany.
Steffen KoschmiederCenter for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University Hospital, Aachen, Germany.
Nicolas ChatainCenter for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University Hospital, Aachen, Germany.
Miguel CastilhoEindhoven University of Technology, Eindhoven, the Netherlands.
Rebekka K SchneiderInstitute for Cell and Tumor Biology, RWTH Aachen University Medical School, Aachen, Germany.
Martin ZenkeDepartment of Cell Biology, Institute for Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany; Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University Hospital, Aachen, Germany. Electronic address: martin.zenke@rwth-aachen.de.
RWTH Aachen University · DEUniversitätsklinikum Aachen · DEDüsseldorf University Hospital · DEEindhoven University of Technology · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The myeloproliferative disease polycythemia vera (PV) driven by the JAK2 V617F mutation can transform into myelofibrosis (post-PV-MF). It remains an open question how JAK2 V617F in hematopoietic stem cells induces MF. Megakaryocytes are major players in murine PV models but are difficult to study in the human setting. We generated induced pluripotent stem cells (iPSCs) from JAK2 V617F PV patients and differentiated them into megakaryocytes. In differentiation assays, JAK2 V617F iPSCs recapitulated the pathognomonic skewed megakaryocytic and erythroid differentiation. JAK2 V617F iPSCs had a TPO-independent and increased propensity to differentiate into megakaryocytes. RNA sequencing of JAK2 V617F iPSC-derived megakaryocytes reflected a proinflammatory, profibrotic phenotype and decreased ribosome biogenesis. In three-dimensional (3D) coculture, JAK2 V617F megakaryocytes induced a profibrotic phenotype through direct cell contact, which was reversed by the JAK2 inhibitor ruxolitinib. The 3D coculture system opens the perspective for further disease modeling and drug discovery.

Indexed as

Induced Pluripotent Stem CellsPolycythemia VeraAnimalsBone MarrowFibrosisHumansJanus Kinase 2MegakaryocytesMiceMutationPhenotypeJAK2 protein, humanJanus Kinase 2

Identifiers

PMID38278152
PMCPMC10874863
OpenAlexW4391219795

What Socratic holds

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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 Socratic graph.