Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo

摘要

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. Homozy-gous humanization of TPO led to increased levels of human en-graftment 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.