Evidence map›Paper›PMID 35314801›Full record

ArticleNature biomedical engineering2022

Screening for modulators of the cellular composition of gut epithelia via organoid models of intestinal stem cell differentiation.

Benjamin E Mead, Kazuki Hattori, Lauren Levy, Shinya Imada, Norihiro Goto, Marko Vukovic, Daphne Sze, Conner Kummerlowe, Juan D Matute, Jinzhi Duan and 6 more

Open access · hybridAbstract read
In one paragraph

Article in Nature biomedical engineering, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

31 citing papers in PubMed, 54 citations in OpenAlex.

  1. Review
  2. Review
  3. New developments and applications of human organoids.Nature reviews. Molecular cell biology · 2026
    Review
  4. Article
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  16. PIKfyve controls dendritic cell function and tumor immunity.bioRxiv : the preprint server for biology · 2024
    Article
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  19. Review
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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

16 authors at 5 institutions in 1 country.

Benjamin E Mead *Harvard-MIT Program in Health Sciences and Technology, MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-7258-7777
Kazuki Hattori *Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-5592-4257
Lauren LevyKoch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-4420-1993
Shinya ImadaKoch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.
Norihiro GotoKoch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.
Marko VukovicHarvard-MIT Program in Health Sciences and Technology, MIT, Cambridge, MA, USA.
Daphne SzeKoch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.
Conner KummerloweKoch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-8641-2916
Juan D MatuteDivision of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1703-8115
Jinzhi DuanDivision of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9351-4956
Robert LangerHarvard-MIT Program in Health Sciences and Technology, MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-4255-0492
Richard S BlumbergDivision of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jose Ordovas-MontanesHarvard Stem Cell Institute, Cambridge, MA, USA.
Ömer H YilmazKoch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-7577-4612
Jeffrey M KarpHarvard-MIT Program in Health Sciences and Technology, MIT, Cambridge, MA, USA. jmkarp@bwh.harvard.edu.ORCID http://orcid.org/0000-0002-4752-7374
Alex K ShalekHarvard-MIT Program in Health Sciences and Technology, MIT, Cambridge, MA, USA. shalek@mit.edu.ORCID http://orcid.org/0000-0001-5670-8778
Brigham and Women's Hospital · USBroad Institute · USAllen Institute · USHarvard–MIT Division of Health Sciences and Technology · USHarvard University · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Angela Nicole Koehler · 1985 to 2026
$93.9M
STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
Quantitative and functional characterization of therapeutic resistance in cancerU54CA217377 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LAUFFENBURGER, DOUGLAS A, MANALIS, SCOTT R · 2017 to 2021
$10.2M
Endoplasmic reticulum stress and intestinal inflammationR01DK088199 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI Richard S Blumberg · 2010 to 2026
$9.6M
Understanding and Improving Platinum Anticancer DrugsR01CA034992 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YILMAZ, OMER · 1985 to 2018
$6.8M
PHOTOPOLYMERIZATION FOR NONINVASIVE CARTILAGE TISSUER01DE013023 · NIDCR · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LANGER, ROBERT SAMUEL · 1998 to 2019
$6.8M
Graduate Training in Computational and Systems BiologyT32GM087237 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BURGE, CHRISTOPHER B · 2009 to 2023
$4.6M
Engineered Induction of a Stem Cell Homing ResponseR01HL095722 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI KARP, JEFFREY MICHAEL · 2010 to 2018
$3.9M
"Bottom - Up" Profiling of Interacting Cellular SystemsDP2GM119419 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SHALEK, ALEX K · 2015 to 2015
$2.3M
Dietary control of stem cells in physiology and cancerR01CA211184 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YILMAZ, OMER · 2017 to 2021
$2.0M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA014051NCI NIH HHS R01 CA034992NCI NIH HHS R01 CA211184NCI NIH HHS U54 CA217377NHLBI NIH HHS R01 HL095722NIDCR NIH HHS R01 DE013023NIDDK NIH HHS P30 DK034854NIDDK NIH HHS R01 DK088199NIGMS NIH HHS DP2 GM119419NIGMS NIH HHS T32 GM087237
6 · The paper itself

Abstract

The cellular composition of barrier epithelia is essential to organismal homoeostasis. In particular, within the small intestine, adult stem cells establish tissue cellularity, and may provide a means to control the abundance and quality of specialized epithelial cells. Yet, methods for the identification of biological targets regulating epithelial composition and function, and of small molecules modulating them, are lacking. Here we show that druggable biological targets and small-molecule regulators of intestinal stem cell differentiation can be identified via multiplexed phenotypic screening using thousands of miniaturized organoid models of intestinal stem cell differentiation into Paneth cells, and validated via longitudinal single-cell RNA-sequencing. We found that inhibitors of the nuclear exporter Exportin 1 modulate the fate of intestinal stem cells, independently of known differentiation cues, significantly increasing the abundance of Paneth cells in the organoids and in wild-type mice. Physiological organoid models of the differentiation of intestinal stem cells could find broader utility for the screening of biological targets and small molecules that can modulate the composition and function of other barrier epithelia.

Indexed as

OrganoidsPaneth CellsAnimalsCell DifferentiationIntestinesMiceStem Cells

Identifiers

PMID35314801
PMCPMC9046079
OpenAlexW4221112718

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.