Saltar al contenido
Merck

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

Nature communications (2018-07-04)
Satoshi Okawa, Carmen Saltó, Srikanth Ravichandran, Shanzheng Yang, Enrique M Toledo, Ernest Arenas, Antonio Del Sol
RESUMEN

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.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Monoclonal Anti-MAP2 antibody produced in mouse, clone HM-2, ascites fluid
Sigma-Aldrich
Anticuerpo anti-LMX-1, serum, from rabbit