Rongvaux, Anthony Willinger, Tim Takizawa, Hitoshi Rathinam, Chozhavendan Auerbach, Wojtek Murphy, Andrew J. Valenzuela, David M. Yancopoulos, George D. Eynon, Elizabeth E. Stevens, Sean Manz, Markus G. Flavell, Richard A. 2011-01-24 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. application/pdf https://susi.usi.ch/global/documents/318966 https://localhost:5000/ark:/12658/srd1318966 https://susi.usi.ch/documents/318966/files/rongvaux_pnas_2011.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1019524108 info:eu-repo/semantics/altIdentifier/ark/12658/srd1318966 info:eu-repo/semantics/openAccess License undefined Proceedings of the national academy of sciences of the United States of America. - 2011, vol. 108, no. 6, p. 2378-2383 info:eu-repo/classification/udc/61 Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo http://purl.org/coar/resource_type/c_6501