Evidence map›Paper›PMID 38472198›Full record

ArticleNature communications2024

Identifying regulators of aberrant stem cell and differentiation activity in colorectal cancer using a dual endogenous reporter system.

Sandor Spisak, David Chen, Pornlada Likasitwatanakul, Paul Doan, Zhixin Li, Pratyusha Bala, Laura Vizkeleti, Viktoria Tisza, Pushpamali De Silva, Marios Giannakis and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

9 citing papers in PubMed, 10 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 6 institutions in 4 countries.

Sandor Spisak *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
David Chen *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Pornlada Likasitwatanakul *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-9689-3231
Paul Doan *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-7329-3495
Zhixin LiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Pratyusha BalaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Laura VizkeletiDepartment of Bioinformatics, Faculty of Medicine, Semmelweis University, 1094, Budapest, Hungary.ORCID 0000-0001-6870-3499
Viktoria TiszaInstitute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary.
Pushpamali De SilvaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-0747-5637
Marios GiannakisDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0001-9012-6982
Brian WolpinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-0455-1032
Jun QiDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-1461-3356
Nilay S SethiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. nilay_sethi@dfci.harvard.edu.ORCID 0000-0002-3748-7559
Broad Institute · USDana-Farber Cancer Institute · USHarvard University · USHUN-REN Research Centre for Natural Sciences · HUSemmelweis University · HUUniversity of Toronto · CA

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI Irene M. Ghobrial · 1985 to 2026
$330.6M
STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
Molecular mechanisms of developmental reprogramming in colorectal cancerR01CA292507 · NCI · DANA-FARBER CANCER INST · PI Nilay Sethi · 2024 to 2026
$2.8M
Integration of early genetic alterations and inflammation in gastroesophageal premalignancyK08DK120930 · NIDDK · DANA-FARBER CANCER INST · PI SETHI, NILAY · 2019 to 2023
$790k
NCI NIH HHS P30 CA006516NCI NIH HHS R01 CA292507NIDDK NIH HHS K08 DK120930NIDDK NIH HHS P30 DK034854
6 · The paper itself

Abstract

Aberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer (CRC). To identify functional mediators of these key cellular programs, we engineer a dual endogenous reporter system by genome-editing the SOX9 and KRT20 loci of human CRC cell lines to express fluorescent reporters, broadcasting aberrant stem cell-like and differentiation activity, respectively. By applying a CRISPR screen targeting 78 epigenetic regulators with 542 sgRNAs to this platform, we identify factors that contribute to stem cell-like activity and differentiation in CRC. Perturbation single cell RNA sequencing (Perturb-seq) of validated hits nominate SMARCB1 of the BAF complex (also known as SWI/SNF) as a negative regulator of differentiation across an array of neoplastic colon models. SMARCB1 is a dependency and required for in vivo growth of human CRC models. These studies highlight the utility of biologically designed endogenous reporter platforms to uncover regulators with therapeutic potential.

Indexed as

Colorectal NeoplasmsRNA, Guide, CRISPR-Cas SystemsCell DifferentiationHumansStem CellsRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID38472198
PMCPMC10933491
OpenAlexW4392683196

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.