Constitutive Expression of MEF2C, LYL1, or LMO2 in CD34(+) HSCs Blocks the in Vitro Differentiation before the T-Cell Commitment Point and Could be Oncogenic in Early T-Cell Progenitor ALL
BLOOD
Authors: Cante-Barrett, Kirsten; Mendes, Rui D.; Smits, Wilco K.; Pieters, Rob; Meijerink, Jules P. P.
Abstract
Single-cell transcriptomics reveals a new dynamical function of transcription factors during embryonic hematopoiesis
ELIFE
Authors: Bergiers, Isabelle; Andrews, Tallulah; Bolukbasi, Ozge Vergel; Buness, Andreas; Janosz, Ewa; Lopez-Anguita, Natalia; Ganter, Kerstin; Kosim, Kinga; Celen, Cemre; Percin, Gulce Itir; Collier, Paul; Baying, Bianka; Benes, Vladimir; Hemberg, Martin; Lancrin, Christophe
Abstract
Recent advances in single-cell transcriptomics techniques have opened the door to the study of gene regulatory networks (GRNs) at the single-cell level. Here, we studied the GRNs controlling the emergence of hematopoietic stem and progenitor cells from mouse embryonic endothelium using a combination of single-cell transcriptome assays. We found that a heptad of transcription factors (Runx1, Gata2, Tal1, Fli1, Lyl1, Erg and Lmo2) is specifically co-expressed in an intermediate population expressing both endothelial and hematopoietic markers. Within the heptad, we identified two sets of factors of opposing functions: one (Erg/Fli1) promoting the endothelial cell fate, the other (Runx1/Gata2) promoting the hematopoietic fate. Surprisingly, our data suggest that even though Fli1 initially supports the endothelial cell fate, it acquires a pro-hematopoietic role when co-expressed with Runx1. This work demonstrates the power of single-cell RNA-sequencing for characterizing complex transcription factor dynamics.