Evidence map›Paper›PMID 34011578›Full record

ArticleGenome research2021

Targeted single-cell RNA sequencing of transcription factors enhances the identification of cell types and trajectories.

Alexandra Pokhilko, Adam E Handel, Fabiola Curion, Viola Volpato, Emma S Whiteley, Sunniva Bøstrand, Sarah E Newey, Colin J Akerman, Caleb Webber, Michael B Clark and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Genome research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing 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

28 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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 4 institutions in 2 countries.

Alexandra PokhilkoTranslational Molecular Neuroscience Group, Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DS, United Kingdom.
Adam E HandelTranslational Molecular Neuroscience Group, Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DS, United Kingdom.
Fabiola CurionWellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom.
Viola VolpatoUK Dementia Research Institute, Cardiff University, Cardiff, CF24 4HQ, United Kingdom.
Emma S WhiteleyDepartment of Pharmacology, University of Oxford, Oxford, OX1 3QT, United Kingdom.
Sunniva BøstrandDepartment of Pharmacology, University of Oxford, Oxford, OX1 3QT, United Kingdom.ORCID 0000-0003-1689-8583
Sarah E NeweyDepartment of Pharmacology, University of Oxford, Oxford, OX1 3QT, United Kingdom.
Colin J AkermanDepartment of Pharmacology, University of Oxford, Oxford, OX1 3QT, United Kingdom.
Caleb WebberUK Dementia Research Institute, Cardiff University, Cardiff, CF24 4HQ, United Kingdom.
Michael B ClarkDepartment of Psychiatry, Warneford Hospital, University of Oxford, Oxford, OX3 7JX, United Kingdom.ORCID 0000-0002-2903-9537
Rory BowdenWellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom.
M Zameel CaderTranslational Molecular Neuroscience Group, Weatherall Institute of Molecular Medicine, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DS, United Kingdom.ORCID 0000-0002-6952-406X
University of Oxford · GBCentre for Human Genetics · GBUK Dementia Research Institute · GBThe University of Melbourne · AU

Funding

Biotechnology and Biological Sciences Research Council BB/S007938/1European Research Council 617670Wellcome TrustWellcome Trust 090532/Z/09/ZWellcome Trust 100643/Z/12/ZWellcome Trust 203141/Z/16/Z
6 · The paper itself

Abstract

Single-cell RNA sequencing (scRNA-seq) is a widely used method for identifying cell types and trajectories in biologically heterogeneous samples, but it is limited in its detection and quantification of lowly expressed genes. This results in missing important biological signals, such as the expression of key transcription factors (TFs) driving cellular differentiation. We show that targeted sequencing of ∼1000 TFs (scCapture-seq) in iPSC-derived neuronal cultures greatly improves the biological information garnered from scRNA-seq. Increased TF resolution enhanced cell type identification, developmental trajectories, and gene regulatory networks. This allowed us to resolve differences among neuronal populations, which were generated in two different laboratories using the same differentiation protocol. ScCapture-seq improved TF-gene regulatory network inference and thus identified divergent patterns of neurogenesis into either excitatory cortical neurons or inhibitory interneurons. Furthermore, scCapture-seq revealed a role for of retinoic acid signaling in the developmental divergence between these different neuronal populations. Our results show that TF targeting improves the characterization of human cellular models and allows identification of the essential differences between cellular populations, which would otherwise be missed in traditional scRNA-seq. scCapture-seq TF targeting represents a cost-effective enhancement of scRNA-seq, which could be broadly applied to improve scRNA-seq resolution.

Indexed as

Induced Pluripotent Stem CellsSingle-Cell AnalysisGene Expression ProfilingGene Regulatory NetworksHumansSequence Analysis, RNATranscription FactorsTranscription Factors

Identifiers

PMID34011578
PMCPMC8168586
OpenAlexW3160339799

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.