Evidence map›Paper›PMID 39503201›Full record

ArticleDevelopment (Cambridge, England)2024

Lgr5 + intestinal stem cells are required for organoid survival after genotoxic injury.

Joseph Lee, Antoine Gleizes, Nicolas V Janto, Lito L Appell, Siyang Sun, Felipe Takaesu, Sarah F Webster, Taylor Hailstock, Nick Barker, Adam D Gracz

Abstract read
In one paragraph

Article in Development (Cambridge, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Tet1 safeguards lineage allocation in intestinal stem cells.bioRxiv : the preprint server for biology · 2025
    Article
4 · The record

Corrections and comments

  • Update of
    2024
5 · Who and what money

Authors and funding

10 authors.

Joseph LeeDepartment of Medicine, Division of Digestive Diseases, Emory University, Atlanta, GA 30322, USA.ORCID 0009-0009-7376-2114
Antoine GleizesDepartment of Medicine, Division of Digestive Diseases, Emory University, Atlanta, GA 30322, USA.ORCID 0009-0002-5490-7743
Nicolas V JantoGraduate Program in Genetics and Molecular Biology, Emory University, Atlanta, GA 30322, USA.ORCID 0000-0003-3717-2220
Lito L AppellDepartment of Medicine, Division of Digestive Diseases, Emory University, Atlanta, GA 30322, USA.ORCID 0000-0002-9965-7613
Siyang SunDepartment of Medicine, Division of Digestive Diseases, Emory University, Atlanta, GA 30322, USA.ORCID 0009-0001-2490-4288
Felipe TakaesuGraduate Program in Biochemistry, Cell and Developmental Biology, Emory University, Atlanta, GA 30322, USA.ORCID 0000-0002-5569-8907
Sarah F WebsterGraduate Program in Biochemistry, Cell and Developmental Biology, Emory University, Atlanta, GA 30322, USA.ORCID 0000-0002-9716-3249
Taylor HailstockGraduate Program in Biochemistry, Cell and Developmental Biology, Emory University, Atlanta, GA 30322, USA.ORCID 0000-0002-1849-100X
Nick BarkerInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673.ORCID 0000-0003-3566-4475
Adam D GraczDepartment of Medicine, Division of Digestive Diseases, Emory University, Atlanta, GA 30322, USA.ORCID 0000-0003-1298-568X

Funding

Atlanta Clinical and Translational Science Institute (ACTSI) RenewalUL1TR000454 · NCATS · EMORY UNIVERSITY · PI STEPHENS, DAVID S · 2012 to 2016
$25.8M
Regulation of intestinal stem cell state by ID3R35GM142503 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Adam David Gracz · 2021 to 2026
$2.5M
U-Rise at the University of New MexicoT34GM145428 · NIGMS · UNIVERSITY OF NEW MEXICO · PI Cristina D. Takacs-Vesbach · 2022 to 2026
$1.7M
Determining the role of Tet1 in facultative intestinal stem cellsF31DK136254 · NIDDK · EMORY UNIVERSITY · PI JANTO, NICOLAS VAUGHAN · 2023 to 2025
$146k
NCATS NIH HHS UL1 TR000454NCATS NIH HHS UL1TR000454NIDDK NIH HHS F31 DK136254NIDDK NIH HHS R35GM142503NIGMS NIH HHS GM145428NIGMS NIH HHS R35 GM142503NIGMS NIH HHS T34 GM145428NIGMS NIH HHS T43GM145428NIH HHS R35GM142503
6 · The paper itself

Abstract

Progenitors and mature cells can maintain the intestinal epithelium by dedifferentiation and facultative intestinal stem cell (fISC) function when active ISCs (aISCs) are lost to damage. Here, we modeled fISC activation in mouse intestinal organoids with doxorubicin (DXR) treatment, a chemotherapeutic known to ablate Lgr5+ aISCs in vivo. Similar fISC gene activation was observed between organoids treated with low versus high DXR, despite significantly decreased survival at the higher dose. aISCs exhibited dose-dependent loss after DXR treatment but survived at doses compatible with organoid survival. We ablated residual aISCs after DXR treatment using a Lgr52A-DTR allele and observed that aISC survival of the initial genotoxic insult is required for organoid survival following DXR treatment. These results suggest that although typical fISC genes are activated by DXR-induced injury in organoids, functional stemness remains dependent on the aISC pool. Finally, we show that human intestinal organoids require higher doses of DXR to induce loss of survival and downregulation of LGR5. Our data establish a reproducible model of DXR-induced injury in intestinal organoids and reveal differences in in vitro responses to an established in vivo damage modality.

Indexed as

DoxorubicinIntestinal MucosaOrganoidsReceptors, G-Protein-CoupledStem CellsAnimalsCell SurvivalDNA DamageHumansIntestinesMiceMice, Inbred C57BLDoxorubicinLGR5 protein, humanLgr5 protein, mouseReceptors, G-Protein-CoupledDoxorubicinIntestinal stem cellsOrganoidsRegeneration

Identifiers

PMID39503201
PMCPMC11634038

What Socratic 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 Socratic graph.