ZEB2 and MEIS1 independently contribute to hematopoiesis via early hematopoietic enhancer activation

Yohko Kitagawa; Akihiro Ikenaka; Ryohichi Sugimura; Akira Niwa; Megumu K Saito

doi:10.1016/j.isci.2023.107893

ZEB2 and MEIS1 independently contribute to hematopoiesis via early hematopoietic enhancer activation

iScience. 2023 Sep 9;26(10):107893. doi: 10.1016/j.isci.2023.107893. eCollection 2023 Oct 20.

Authors

Yohko Kitagawa¹, Akihiro Ikenaka¹, Ryohichi Sugimura¹, Akira Niwa¹, Megumu K Saito¹

Affiliation

¹ Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.

Abstract

Cell differentiation is achieved by acquiring a cell type-specific transcriptional program and epigenetic landscape. While the cell type-specific patterning of enhancers has been shown to precede cell fate decisions, it remains unclear how regulators of these enhancers are induced to initiate cell specification and how they appropriately restrict cells that differentiate. Here, using embryonic stem cell-derived hematopoietic cell differentiation cultures, we show the activation of some hematopoietic enhancers during arterialization of hemogenic endothelium, a prerequisite for hematopoiesis. We further reveal that ZEB2, a factor involved in the transcriptional regulation of arterial endothelial cells, and a hematopoietic regulator MEIS1 are independently required for activating these enhancers. Concomitantly, ZEB2 or MEIS1 deficiency impaired hematopoietic cell development. These results suggest that multiple regulators expressed from an earlier developmental stage non-redundantly contribute to the establishment of hematopoietic enhancer landscape, thereby restricting cell differentiation despite the unrestricted expression of these regulators to hematopoietic cells.

Keywords: Biological sciences; Developmental biology; Natural sciences.