Evidence map›Paper›PMID 42275222›Full record

ArticleCell reports2026

Synergistic cooperation between progranulin and Jak2/Stat3 signaling determines definitive myeloid cell fate.

Abbigail McCune, Masuma Khatun Usha, Inga Baldus, C J Willett, Noemi Ferrito, Radwa Barakat, Emilee Clemensen, Elizabeth Snella, Mark Morton, Jesus Lacal and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Abbigail McCuneDepartment of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA.
Masuma Khatun UshaDepartment of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA.
Inga BaldusDepartment of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA.
C J WillettRaymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Noemi FerritoDepartment of Microbiology and Genetics, University of Salamanca, 37007 Salamanca, Spain.
Radwa BarakatDepartment of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA; Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Benha University, Qalyubia 13511, Egypt.
Emilee ClemensenDepartment of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA.
Elizabeth SnellaDepartment of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA.
Mark MortonDepartment of Veterinary Pathology, Iowa State University, Ames, IA 50011, USA.
Jesus LacalDepartment of Microbiology and Genetics, University of Salamanca, 37007 Salamanca, Spain.
Giulia PavaniRaymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Clyde A CampbellDepartment of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA.
Raquel Espin-PalazonDepartment of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA. Electronic address: espin@iastate.edu.

Funding

Molecular dissection of Hematopoietic Stem Cell specification triggered by inflammatory mediatorsR01DK131162 · NIDDK · IOWA STATE UNIVERSITY · PI Raquel Espin Palazon · 2022 to 2026
$2.1M
The impact of inflammation on hematopoietic stem cell specificationK01DK115661 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESPÍN PALAZÓN, RAQUEL · 2017 to 2021
$834k
In vivo assessment of granulin dependent myeloid cell formationR03DK125661 · NIDDK · IOWA STATE UNIVERSITY · PI ESPÍN PALAZÓN, RAQUEL · 2020 to 2021
$230k
NIDDK NIH HHS K01 DK115661NIDDK NIH HHS R01 DK131162NIDDK NIH HHS R03 DK125661
6 · The paper itself

Abstract

Perturbations in cell fate disrupt tissue homeostasis and drive diseases such as cancer. The JAK/STAT pathway is central to hematopoietic malignancies, yet its regulators in cell fate decisions remain poorly defined. Here, we identify progranulin (GRN) as a critical determinant of myeloid fate through the regulation of JAK2/STAT3 signaling. Using inducible stat3 and grna zebrafish models, knockout approaches, FACS, transcriptomics, and CUT&RUN, we show that Stat3 induces grna, which in turn amplifies stat3 expression, reinforcing myeloid over erythroid commitment. Lineage tracing and live imaging reveal that this Grna/Stat3 feedback operates during definitive, but not primitive, myelopoiesis. Functionally, definitive myeloid cells drive tissue repair, whereas primitive counterparts are less effective. Myeloid differentiation in a human leukemia line required GRN co-stimulation of JAK2/STAT3, highlighting its conserved role in fate determination. These findings uncover a regulatory axis controlling hematopoietic commitment and identify GRN as a potential therapeutic target in diseases with aberrant JAK2/STAT3 activation.

Indexed as

Janus Kinase 2Myeloid CellsProgranulinsSTAT3 Transcription FactorZebrafish ProteinsAnimalsCell DifferentiationCell LineageHumansSignal TransductionZebrafishJanus Kinase 2ProgranulinsSTAT3 Transcription FactorZebrafish ProteinsCP: developmental biologyCP: stem cell researchdevelopmental hematopoiesisembryonic macrophagesJAK2/STAT3leukemiamyeloid differentiationprogranulintissue regenerationzebrafish

Identifiers

PMID42275222
PMCPMC13366427

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.