Format

Send to

Choose Destination
Nat Commun. 2018 Jul 3;9(1):2595. doi: 10.1038/s41467-018-05016-8.

Transcriptional synergy as an emergent property defining cell subpopulation identity enables population shift.

Author information

1
Computational Biology Group, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 6, avenue du Swing, L-4367, Belvaux, Luxembourg.
2
Department of Medical Biochemistry and Biophysics, Laboratory of Molecular Neurobiology, Biomedicum 6C, Solnav├Ągen 9, Karolinska Institutet, 17177, Stockholm, Sweden.
3
Novo Nordisk Research Centre Oxford (NNRCO), Cellular and Systems Genomics, Oxford, OX3 7BN, United Kingdom.
4
Computational Biology Group, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 6, avenue du Swing, L-4367, Belvaux, Luxembourg. antonio.delsol@uni.lu.
5
Moscow Institute of Physics and Technology, Dolgoprudny, 141701, Russia. antonio.delsol@uni.lu.

Abstract

Single-cell RNA sequencing allows defining molecularly distinct cell subpopulations. However, the identification of specific sets of transcription factors (TFs) that define the identity of these subpopulations remains a challenge. Here we propose that subpopulation identity emerges from the synergistic activity of multiple TFs. Based on this concept, we develop a computational platform (TransSyn) for identifying synergistic transcriptional cores that determine cell subpopulation identities. TransSyn leverages single-cell RNA-seq data, and performs a dynamic search for an optimal synergistic transcriptional core using an information theoretic measure of synergy. A large-scale TransSyn analysis identifies transcriptional cores for 186 subpopulations, and predicts identity conversion TFs between 3786 pairs of cell subpopulations. Finally, TransSyn predictions enable experimental conversion of human hindbrain neuroepithelial cells into medial floor plate midbrain progenitors, capable of rapidly differentiating into dopaminergic neurons. Thus, TransSyn can facilitate designing strategies for conversion of cell subpopulation identities with potential applications in regenerative medicine.

PMID:
29968757
PMCID:
PMC6030214
DOI:
10.1038/s41467-018-05016-8
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center