Evidence map›Paper›PMID 38072195›Full record

ArticleThe Journal of allergy and clinical immunology2024

Recapitulating primary immunodeficiencies with expanded potential stem cells: Proof of concept with STAT1 gain of function.

Xueyan Liu, Vera S F Chan, Kenneth G C Smith, Chang Ming, Chung Sze Or, Faria T W Tsui, Bo Gao, Matthew C Cook, Pentao Liu, Chak Sing Lau and 1 more

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

Article in The Journal of allergy and clinical immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 22% 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Italian pediatric experts' consensus statement on diagnosis and management of primary atopic disorders.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2025
    Guideline
  2. Review
  3. Article
  4. Article
  5. Review
  6. Hereditary Angioedema (HAE) in China: Advancing Awareness, Access, Advocacy and Alliances From the Greater Bay Area to the Global HAE Community.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2025
    Review
  7. Article
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

11 authors at 4 institutions in 4 countries.

Xueyan LiuCentre for Translational Stem Cell Biology, University of Hong Kong, Hong Kong SAR, China; Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, China.
Vera S F ChanCentre for Translational Stem Cell Biology, University of Hong Kong, Hong Kong SAR, China; Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, China.
Kenneth G C SmithCentre for Translational Stem Cell Biology, University of Hong Kong, Hong Kong SAR, China; Department of Medicine, University of Cambridge School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.
Chang MingCentre for Translational Stem Cell Biology, University of Hong Kong, Hong Kong SAR, China; School of Biomedical Sciences, University of Hong Kong, Hong Kong SAR, China.
Chung Sze OrCentre for Translational Stem Cell Biology, University of Hong Kong, Hong Kong SAR, China; Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, China.
Faria T W TsuiCentre for Translational Stem Cell Biology, University of Hong Kong, Hong Kong SAR, China; Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, China.
Bo GaoCentre for Translational Stem Cell Biology, University of Hong Kong, Hong Kong SAR, China; School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong SAR, China.
Matthew C CookCentre for Translational Stem Cell Biology, University of Hong Kong, Hong Kong SAR, China; Department of Medicine, University of Cambridge School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.
Pentao LiuCentre for Translational Stem Cell Biology, University of Hong Kong, Hong Kong SAR, China; School of Biomedical Sciences, University of Hong Kong, Hong Kong SAR, China.
Chak Sing LauCentre for Translational Stem Cell Biology, University of Hong Kong, Hong Kong SAR, China; Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, China.
Philip Hei LiCentre for Translational Stem Cell Biology, University of Hong Kong, Hong Kong SAR, China; Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, China. Electronic address: liphilip@hku.hk.
Queen Mary Hospital · CNUniversity of Cambridge · GBUniversity of Hong Kong · HKChinese University of Hong Kong · HK

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundInborn errors of immunity (IEI) often lack specific disease models and personalized management. Signal transducer and activator of transcription (STAT)-1 gain of function (GoF) is such example of an IEI with diverse clinical phenotype with unclear pathomechanisms and unpredictable response to therapy. Limitations in obtaining fresh samples for functional testing and research further highlights the need for patient-specific ex vivo platforms.

objectiveUsing STAT1-GoF as an example IEI, we investigated the potential of patient-derived expanded potential stem cells (EPSC) as an ex vivo platform for disease modeling and personalized treatment.

methodsWe generated EPSC derived from individual STAT1-GoF patients. STAT1 mutations were confirmed with Sanger sequencing. Functional testing including STAT1 phosphorylation/dephosphorylation and gene expression with or without Janus activating kinase inhibitors were performed. Functional tests were repeated on EPSC lines with GoF mutations repaired by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) editing.

resultsEPSC were successfully reprogrammed from STAT1-GoF patients and expressed the same pluripotent makers as controls, with distinct morphologic differences. Patient-derived EPSC recapitulated the functional abnormalities of index STAT1-GoF patients with STAT1 hyperphosphorylation and increased expression of STAT1 and its downstream genes (IRF1, APOL6, and OAS1) after IFN-γ stimulation. Addition of ruxolitinib and baricitinib inhibited STAT1 hyperactivation in STAT1-GoF EPSC in a dose-dependent manner, which was not observed with tofacitinib. Corrected STAT1 phosphorylation and downstream gene expression were observed among repaired STAT1-GoF EPSC cell lines.

conclusionThis proof-of-concept study demonstrates the potential of our patient-derived EPSC platform to model STAT1-GoF. We propose this platform when researching, recapitulating, and repairing other IEI in the future.

Indexed as

Gain of Function MutationSTAT1 Transcription FactorStem CellsHumansMutationPhosphorylationSTAT1 protein, humanSTAT1 Transcription FactorCRISPR/Cas9expanded potentialgain of functiongene editingimmunodeficiencyinborn errors of immunityJanus activating kinase (JAK) inhibitormodelpersonalizedphosphorylationsignal transducer and activator of transcription 1 (STAT1)stem cell

Identifiers

PMID38072195
PMCPMC7619439
OpenAlexW4389504251

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.