Evidence map›Paper›PMID 19759516›Full record

ArticleThe Journal of clinical investigation2009

SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production.

Gang Chen, Thomas R Korfhagen, Yan Xu, Joseph Kitzmiller, Susan E Wert, Yutaka Maeda, Alexander Gregorieff, Hans Clevers, Jeffrey A Whitsett

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 268 papers.

0numbers the graph read from it
0cells of the map it votes in
268citing papers in PubMed
17.0field-weighted citation impact, top 1% 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

268 citing papers in PubMed, 400 citations in OpenAlex.

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  19. Specialized gas-exchange endothelium of the zebrafish gill.bioRxiv : the preprint server for biology · 2025
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208 more citing papers are in PubMed but not listed here.

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

9 authors at 1 institution in 1 country.

Gang ChenThe Perinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and the University of Cincinnati School of Medicine, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.
Thomas R Korfhagen
Yan Xu
Joseph Kitzmiller
Susan E Wert
Yutaka Maeda
Alexander Gregorieff
Hans Clevers
Jeffrey A Whitsett
Hubrecht Institute for Developmental Biology and Stem Cell Research · NL

Funding

Transcriptional Programming of Asthma Related Pathology in Respiratory EpitheliaR01HL095580 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI WHITSETT, JEFFREY A · 2009 to 2017
$4.7M
Transcriptional Control of Respiratory Epithelial Progenitor CellsR01HL090156 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI WHITSETT, JEFFREY A · 2007 to 2010
$2.1M
NHLBI NIH HHS HL090156NHLBI NIH HHS HL095580NHLBI NIH HHS R01 HL090156NHLBI NIH HHS R01 HL095580
6 · The paper itself

Abstract

Various acute and chronic inflammatory stimuli increase the number and activity of pulmonary mucus-producing goblet cells, and goblet cell hyperplasia and excess mucus production are central to the pathogenesis of chronic pulmonary diseases. However, little is known about the transcriptional programs that regulate goblet cell differentiation. Here, we show that SAM-pointed domain-containing Ets-like factor (SPDEF) controls a transcriptional program critical for pulmonary goblet cell differentiation in mice. Initial cell-lineage-tracing analysis identified nonciliated secretory epithelial cells, known as Clara cells, as the progenitors of goblet cells induced by pulmonary allergen exposure in vivo. Furthermore, in vivo expression of SPDEF in Clara cells caused rapid and reversible goblet cell differentiation in the absence of cell proliferation. This was associated with enhanced expression of genes regulating goblet cell differentiation and protein glycosylation, including forkhead box A3 (Foxa3), anterior gradient 2 (Agr2), and glucosaminyl (N-acetyl) transferase 3, mucin type (Gcnt3). Consistent with these findings, levels of SPDEF and FOXA3 were increased in mouse goblet cells after sensitization with pulmonary allergen, and the proteins were colocalized in goblet cells lining the airways of patients with chronic lung diseases. Deletion of the mouse Spdef gene resulted in the absence of goblet cells in tracheal/laryngeal submucosal glands and in the conducting airway epithelium after pulmonary allergen exposure in vivo. These data show that SPDEF plays a critical role in regulating a transcriptional network mediating the goblet cell differentiation and mucus hyperproduction associated with chronic pulmonary disorders.

Indexed as

Gene Expression RegulationGene Regulatory NetworksAnimalsCell DifferentiationCell LineGene Expression ProfilingGoblet CellsHepatocyte Nuclear Factor 3-gammaHumansLungLung DiseasesMiceMice, KnockoutMucinsMucoproteinsMucusAgr2 protein, mouseFoxa3 protein, mouseHepatocyte Nuclear Factor 3-gammaMucinsMucoproteinsOncogene ProteinsProto-Oncogene Proteins c-etsSpdef protein, mouse

Identifiers

PMID19759516
PMCPMC2752084
OpenAlexW2015250685

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.