Zinc Finger Protein 521 regulates early hematopoiesis through cell extrinsic mechanisms in the bone marrow microenvironment

Zinc finger protein 521 (ZFP521), a DNA-binding protein containing 30 Krüppel-like zinc fingers, has been implicated in the differentiation of multiple cell types, including hematopoietic stem and progenitor cells (HSPC) and B lymphocytes. Here, we report a novel role for ZFP521 in regulating the earliest stages of hematopoiesis and lymphoid cell development through soluble microenvironmental proteins. Mice with inactivated Zfp521 genes (Zfp521-/-) possess reduced frequencies and numbers of hematopoietic stem and progenitor cells, common lymphoid progenitors, and B and T cell precursors. Notably, ZFP521 deficiency changes BM microenvironment cytokine levels and gene expression within resident HSPC, consistent with a skewing of hematopoiesis away from lymphopoiesis and towards granulopoiesis. These results advance our understanding of ZFP521’s role in normal hematopoiesis, justifying further research to assess its potential as a target for cancer therapies. RNA-seq transcriptome analysis of two independent RNA samples each from wild type or Zfp521 knockout HSC pools from mice.