Zinc Finger Protein 521 Regulates Early Hematopoiesis through Cell-Extrinsic Mechanisms in the Bone Marrow Microenvironment

• Published in: Molecular and cellular biology Vol. 38; no. 17
• Main Authors: Fleenor, Courtney J., Arends, Tessa, Lei, Hong, Åhsberg, Josefine, Okuyama, Kazuki, Kuruvilla, Jacob, Cristobal, Susana, Rabe, Jennifer L., Pandey, Ahwan, Danhorn, Thomas, Straign, Desiree, Espinosa, Joaquin M., Warming, Søren, Pietras, Eric M., Sigvardsson, Mikael, Hagman, James R.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01-09-2018; American Society for Microbiology
• Subjects: bone marrow microenvironment; hematopoietic progenitors; hematopoietic stem cell; lymphopoiesis; ZFP521/ZNF521; hematopoietic stem cell; lymphopoiesis; ZFP521/ZNF521; hematopoietic progenitors; bone marrow microenvironment
• ISSN: 1098-5549; 0270-7306; 1098-5549
• DOI: 10.1128/MCB.00603-17

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 via a cell-extrinsic mechanism. 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 bone marrow microenvironment cytokine levels and gene expression within resident HSPC, consistent with a skewing of hematopoiesis away from lymphopoiesis. 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.