Zbtb46 ‐dependent altered developmental program in embryonic stem cell‐derived blood cell progenitors

In this study, we engineered murine Zbtb46-inducible embryonic stem cell lines and characterize their hematopoietic differentiation capacity. We found here that enforced expression of Zbtb46 strongly suppressed the myeloid blood cell development; moreover, this transcription factor negatively influenced the cell proliferation. On the other hand, ectopic expression of Zbtb46 was coupled with the enhanced production of CD105+ cells and the augmented erythroid blood cell development. AbstractZbtb46 is a recently identified dendritic cell (DC)-specific transcription factor with poorly defined biology. Although Zbtb46 is highly expressed in conventional DCs, evidence also points to its presence in erythroid progenitors and endothelial cells suggesting that this factor might influence the early hematopoietic development. Here, we probe the effect of this transcription factor in embryonic stem cell (ESC)-derived blood cell progenitors using chemically inducible mouse cell lines. Unexpectedly, forced expression of this protein elicited a broad repressive effect at the early stage of ESC differentiation. Ectopic expression of Zbtb46 interfered with the mesoderm formation and cell proliferation was also negatively impacted. More importantly, reduced number of CD11b+ myeloid blood cells were generated from ESC-derived Flk1+ mesoderm cells in the presence of Zbtb46. Consistent with this finding, our gene expression profiling revealed that numerous myeloid and immune response related gene...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research