Journal article

Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo

  • Rongvaux, Anthony Department of Immunobiology, Yale University School of Medicine, New Haven - Bill and Melinda Gates Foundation Grand Challenges in Global Health GC#4 Consortia, Yale University School of Medicine, New Haven
  • Willinger, Tim Department of Immunobiology, Yale University School of Medicine, New Haven - Bill and Melinda Gates Foundation Grand Challenges in Global Health GC#4 Consortia, Yale University School of Medicine, New Haven
  • Takizawa, Hitoshi Bill and Melinda Gates Foundation Grand Challenges in Global Health GC#4 Consortia, Yale University School of Medicine, New Haven - Division of Hematology, University Hospital Zurich, Zurich, Switzerland - Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Rathinam, Chozhavendan Department of Immunobiology, Yale University School of Medicine, New Haven - Bill and Melinda Gates Foundation Grand Challenges in Global Health GC#4 Consortia, Yale University School of Medicine, New Haven
  • Auerbach, Wojtek Regeneron Pharmaceuticals, Inc.,Tarrytown, NY
  • Murphy, Andrew J. Regeneron Pharmaceuticals, Inc.,Tarrytown, NY
  • Valenzuela, David M. Regeneron Pharmaceuticals, Inc.,Tarrytown, NY
  • Yancopoulos, George D. Regeneron Pharmaceuticals, Inc.,Tarrytown, NY
  • Eynon, Elizabeth E. Department of Immunobiology, Yale University School of Medicine, New Haven - Bill and Melinda Gates Foundation Grand Challenges in Global Health GC#4 Consortia, Yale University School of Medicine, New Haven - Howard Hughes Medical Institute, Yale University School of Medicine, New Haven
  • Stevens, Sean Bill and Melinda Gates Foundation Grand Challenges in Global Health GC#4 Consortia, Yale University School of Medicine, New Haven - Regeneron Pharmaceuticals, Inc., Tarrytown, NY
  • Manz, Markus G. Bill and Melinda Gates Foundation Grand Challenges in Global Health GC#4 Consortia, Yale University School of Medicine, New Haven - Division of Hematology, University Hospital Zurich, Zurich, Switzerland - Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Flavell, Richard A. Department of Immunobiology, Yale University School of Medicine, New Haven - Bill and Melinda Gates Foundation Grand Challenges in Global Health GC#4 Consortia, Yale University School of Medicine, New Haven- Howard Hughes Medical Institute, Yale University School of Medicine, New Haven
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    24.01.2011
Published in:
  • Proceedings of the national academy of sciences of the United States of America. - 2011, vol. 108, no. 6, p. 2378-2383
English Hematopoietic stem cells (HSCs) both self-renew and give rise to all blood cells for the lifetime of an individual. Xenogeneic mouse models are broadly used to study human hematopoietic stem and progenitor cell biology in vivo. However, maintenance, differentiation, and function of human hematopoietic cells are suboptimal in these hosts. Thrombopoietin (TPO) has been demonstrated as a crucial cytokine supporting maintenance and self-renewal of HSCs. We generated RAG2−/−γc−/− mice in which we replaced the gene encoding mouse TPO by its human homolog. Homozygous humanization of TPO led to increased levels of human engraftment in the bone marrow of the hosts, and multilineage differentiation of hematopoietic cells was improved, with an increased ratio of myelomonocytic verus lymphoid lineages. Moreover, maintenance of human stem and progenitor cells was improved, as demonstrated by serial transplantation. Therefore, RAG2−/−γc−/− TPO-humanized mice represent a useful model to study human hematopoiesis in vivo.
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  • English
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Medicine
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https://susi.usi.ch/usi/documents/318966
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