TY - JOUR TI - Zbtb46-dependent altered developmental program in embryonic stem cell-derived blood cell progenitors AU - Boto, Pal AU - Gerzsenyi, Timea Beatrix AU - Lengyel, Adel AU - Szunyog, Balint AU - Szatmari, Istvan T2 - STEM CELLS AB - Zbtb46 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 genes, including Irf8, exhibited lower expression in the Zbtb46-primed cells. Despite these repressive effects, however, Zbtb46 overexpression was associated with enhanced formation of erythroid blood cell colonies and increased adult hemoglobin (Hbb-b1) expression at the early phase of ESC differentiation. Moreover, elevated percent of CD105 (Endoglin) positive cells were detected in the Zbtb46-primed samples. In summary, our results support that Zbtb46 suppresses the ESC-derived myeloid development and diverts mesoderm cells toward erythroid developmental pathway. Moreover, our transcriptomic data provide a resource for exploration of the Zbtb46 regulatory network in ESC-derived progenitors. © AlphaMed Press 2021 Significance Statement The transcription factor Zbtb46 is hallmark of dendritic cells; however, the exact function of this protein is still poorly characterized. In this study, Zbtb46 was probed in embryonic stem cell-derived blood cell progenitors using chemically inducible transgenic cell lines. The authors found that forced expression of Zbtb46 profoundly suppressed the myeloid blood cell development; on the other hand, ectopic expression of this factor enhanced the erythroid colony formation and the adult hemoglobin expression. These findings suggest that Zbtb46 can act as a molecular regulator to redirect the early blood cell differentiation program in pluripotent stem cell-derived progenitors. DO - https://doi.org/10.1002/stem.3424 DP - Wiley Online Library VL - n/a IS - n/a LA - en SN - 1549-4918 UR - https://stemcellsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/stem.3424 Y2 - 2021/06/01/17:47:17 KW - Zbtb46 KW - embryonic stem cell KW - erythropoiesis KW - hematopoietic development KW - transcription factor ER -