Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo
| Autor: | Richard A. Flavell, David M. Valenzuela, George D. Yancopoulos, Markus G. Manz, Wojtek Auerbach, Chozhavendan Rathinam, Sean Stevens, Elizabeth E. Eynon, Hitoshi Takizawa, Anthony Rongvaux, Andrew J. Murphy, Tim Willinger |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_treatment
Transplantation Heterologous Mice Transgenic Stem cell factor Hematopoietic stem cell transplantation Biology Mice medicine Animals Humans Gene Knock-In Techniques Progenitor cell Thrombopoietin Transplantation Chimera Multidisciplinary Hematopoietic Stem Cell Transplantation hemic and immune systems Biological Sciences Hematopoiesis Cell biology Haematopoiesis Cytokine medicine.anatomical_structure Immunology embryonic structures Bone marrow Stem cell |
| Popis: | 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 −/− γ c −/− 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 −/− γ c −/− TPO-humanized mice represent a useful model to study human hematopoiesis in vivo. |
| Databáze: | OpenAIRE |
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