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Zinc Finger Protein 521 Regulates Early Hematopoiesis through Cell-Extrinsic Mechanisms in the Bone Marrow Microenvironment
Natl Jewish Hlth, CO 80206 USA; Univ Colorado, CO 80045 USA; Globeimmune Inc, CO USA.
Univ Colorado, CO 80045 USA.
Natl Jewish Hlth, CO 80206 USA; Univ Colorado, CO 80045 USA.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
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2018 (English)In: Molecular and Cellular Biology, ISSN 0270-7306, E-ISSN 1098-5549, Vol. 38, no 17, article id UNSP e00603-17Article in journal (Refereed) Published
Abstract [en]

Zinc finger protein 521 (ZFP521), a DNA-binding protein containing 30 Kruppel-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 ZFP521s role in normal hematopoiesis, justifying further research to assess its potential as a target for cancer therapies.

Place, publisher, year, edition, pages
AMER SOC MICROBIOLOGY , 2018. Vol. 38, no 17, article id UNSP e00603-17
Keywords [en]
hematopoietic stem cell; ZFP521/ZNF521; lymphopoiesis; bone marrow microenvironment; hematopoietic progenitors
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-150854DOI: 10.1128/MCB.00603-17ISI: 000441507400005PubMedID: 29915154OAI: oai:DiVA.org:liu-150854DiVA, id: diva2:1245909
Note

Funding Agencies|National Institutes of Health [R01AI081878, R01AI098417, R21AI115696, R01CA117907, K01DK098315]; Wendy Siegel Fund for Leukemia and Cancer Research; Mary Miller and Charlotte Fonfara-Larose Leukemia and Down Syndrome Research Fund; NIH Institutional National Service Award [2T32AI074491]; NIH [F31HL138754]; Victor W. Bolie and Earleen D. Bolie Graduate Scholarship Fund; Swedish Cancer Foundation; Swedish Medical Research Council

Available from: 2018-09-06 Created: 2018-09-06 Last updated: 2018-10-08

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