Evidence map›Paper›PMID 34611171›Full record

ArticleNature communications2021

Single-cell analysis of patient-derived PDAC organoids reveals cell state heterogeneity and a conserved developmental hierarchy.

Teresa G Krieger, Solange Le Blanc, Julia Jabs, Foo Wei Ten, Naveed Ishaque, Katharina Jechow, Olivia Debnath, Carl-Stephan Leonhardt, Anamika Giri, Roland Eils and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
7.4field-weighted citation impact, top 2% 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

77 citing papers in PubMed, 114 citations in OpenAlex.

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17 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

12 authors at 3 institutions in 3 countries.

Teresa G Krieger *Digital Health Center, Berlin Institute of Health (BIH)/Charité-Universitätsmedizin Berlin, Berlin, Germany.
Solange Le Blanc *European Pancreas Center, Department of General Surgery, Heidelberg University Hospital, Heidelberg, Germany.
Julia Jabs *Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Foo Wei TenDigital Health Center, Berlin Institute of Health (BIH)/Charité-Universitätsmedizin Berlin, Berlin, Germany.ORCID 0000-0003-0839-6815
Naveed IshaqueDigital Health Center, Berlin Institute of Health (BIH)/Charité-Universitätsmedizin Berlin, Berlin, Germany.ORCID 0000-0002-8426-901X
Katharina JechowDigital Health Center, Berlin Institute of Health (BIH)/Charité-Universitätsmedizin Berlin, Berlin, Germany.ORCID 0000-0002-3382-3527
Olivia DebnathDigital Health Center, Berlin Institute of Health (BIH)/Charité-Universitätsmedizin Berlin, Berlin, Germany.
Carl-Stephan LeonhardtEuropean Pancreas Center, Department of General Surgery, Heidelberg University Hospital, Heidelberg, Germany.
Anamika GiriDivision of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Roland EilsDigital Health Center, Berlin Institute of Health (BIH)/Charité-Universitätsmedizin Berlin, Berlin, Germany. roland.eils@charite.de.ORCID 0000-0002-0034-4036
Oliver StrobelEuropean Pancreas Center, Department of General Surgery, Heidelberg University Hospital, Heidelberg, Germany. oliver.strobel@meduniwien.ac.at.ORCID 0000-0001-5100-8449
Christian ConradDigital Health Center, Berlin Institute of Health (BIH)/Charité-Universitätsmedizin Berlin, Berlin, Germany. christian.conrad@charite.de.ORCID 0000-0001-7036-342X
German Cancer Research Center · DEBerlin Institute of Health at Charité - Universitätsmedizin Berlin · DEHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is projected to be the second leading cause of cancer mortality by 2030. Bulk transcriptomic analyses have distinguished 'classical' from 'basal-like' tumors with more aggressive clinical behavior. We derive PDAC organoids from 18 primary tumors and two matched liver metastases, and show that 'classical' and 'basal-like' cells coexist in individual organoids. By single-cell transcriptome analysis of PDAC organoids and primary PDAC, we identify distinct tumor cell states shared across patients, including a cycling progenitor cell state and a differentiated secretory state. Cell states are connected by a differentiation hierarchy, with 'classical' cells concentrated at the endpoint. In an imaging-based drug screen, expression of 'classical' subtype genes correlates with better drug response. Our results thus uncover a functional hierarchy of PDAC cell states linked to transcriptional tumor subtypes, and support the use of PDAC organoids as a clinically relevant model for in vitro studies of tumor heterogeneity.

Indexed as

Biomarkers, TumorGene Expression Regulation, NeoplasticHumansOrganoidsSingle-Cell AnalysisBiomarkers, Tumor

Identifiers

PMID34611171
PMCPMC8492851
OpenAlexW3204825643

What OpenQuestion holds

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LicenceCC BY
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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.