Evidence map›Paper›PMID 40930101›Full record

ArticleCell genomics2025

Sensitive dissection of a genomic regulatory landscape using bulk and targeted single-cell activation.

Dubravka Vučićević, Che-Wei Hsu, Lorena Sofia Lopez Zepeda, Martin Burkert, Antje Hirsekorn, Ilija Bilić, Nicolai Kastelić, Markus Landthaler, Scott Allen Lacadie, Uwe Ohler

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Dubravka VučićevićComputational Regulatory Genomics, Berlin Institute for Medical Systems Biology of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany. Electronic address: vucicevic.dubravka@gmail.com.
Che-Wei HsuComputational Regulatory Genomics, Berlin Institute for Medical Systems Biology of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany.
Lorena Sofia Lopez ZepedaComputational Regulatory Genomics, Berlin Institute for Medical Systems Biology of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany.
Martin BurkertComputational Regulatory Genomics, Berlin Institute for Medical Systems Biology of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany.
Antje HirsekornComputational Regulatory Genomics, Berlin Institute for Medical Systems Biology of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany.
Ilija BilićComputational Regulatory Genomics, Berlin Institute for Medical Systems Biology of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany.
Nicolai KastelićRNA Biology and Posttranscriptional Regulation, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine, 10115 Berlin, Germany.
Markus LandthalerRNA Biology and Posttranscriptional Regulation, Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine, 10115 Berlin, Germany.
Scott Allen LacadieComputational Regulatory Genomics, Berlin Institute for Medical Systems Biology of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany. Electronic address: scott.lacadie@mdc-berlin.de.
Uwe OhlerComputational Regulatory Genomics, Berlin Institute for Medical Systems Biology of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany; Department of Biology, Humboldt Universität Berlin, 10117 Berlin, Germany. Electronic address: uwe.ohler@mdc-berlin.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Enhancers are known to spatiotemporally regulate gene transcription, yet the identification of enhancers and their target genes is often indirect, low resolution, and/or assumptive. To identify and functionally perturb enhancers at their endogenous sites, we performed a pooled tiling CRISPR activation (CRISPRa) screen surrounding PHOX2B, a master regulator of neuronal cell fate and a key player in neuroblastoma, and found many CRISPRa-responsive elements (CaREs) that alter cellular growth. To determine CaRE target genes, we developed TESLA-seq (targeted single-cell activation), which combines CRISPRa screening with targeted single-cell RNA sequencing and enables the parallel readout of the effect of hundreds of enhancers on all genes in the locus. While most TESLA-revealed CaRE-gene relationships involved neuroblastoma-related regulatory elements, we found many CaREs and target connections normally active only in other tissues. This highlights the power of TESLA-seq to reveal gene regulatory networks, including edges active outside of a given experimental system.

Indexed as

GenomicsSingle-Cell AnalysisCell Line, TumorCRISPR-Cas SystemsEnhancer Elements, GeneticGene Regulatory NetworksHomeodomain ProteinsHumansNeuroblastomaTranscription FactorsHomeodomain ProteinsNBPhox proteinTranscription FactorsCRISPRaCRISPR screenenhancersPHOX2BSHISA3single-cell genomicstargeted scRNA-seqTESLA-seqtranscription

Identifiers

PMID40930101
PMCPMC12790989

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Registered trials

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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.