期刊
SCIENTIFIC REPORTS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41598-022-07041-6
关键词
-
资金
- NIH [R21AI103656]
- Tobacco-Related Disease Research Program (TRDRP) Predoctoral Fellowship [T31DT1690]
- California Institute for Regenerative Medicine (CIRM) [TG2-01157]
- NIGMS IRACDA Postdoctoral Training Grant [K12GM139185]
- CIRM [CL1-00506, FA1-00617-1, SCR_021353, SCR_021135, RRIDs SCR_021149]
These new mouse models allow for specific induction of death in hematopoietic cells or HSCs, providing a new platform to study HSC performance under steady-state conditions. These models can be used to test the necessity of HSCs for long-term hematopoiesis in vivo, as well as to explore the mechanisms regulating HSC engraftment and hematopoietic homeostasis.
Hematopoietic stem cell (HSC) multipotency and self-renewal are typically defined through serial transplantation experiments. Host conditioning is necessary for robust HSC engraftment, likely by reducing immune-mediated rejection and by clearing limited HSC niche space. Because irradiation of the recipient mouse is non-specific and broadly damaging, there is a need to develop alternative models to study HSC performance at steady-state and in the absence of radiation-induced stress. We have generated and characterized two new mouse models where either all hematopoietic cells or only HSCs can be specifically induced to die in vivo or in vitro. Hematopoietic-specific Vav1-mediated expression of a loxP-flanked diphtheria-toxin receptor (DTR) renders all hematopoietic cells sensitive to diphtheria toxin (DT) in Vav-DTR mice. Crossing these mice to Flk2-Cre mice results in HSC-DTR mice which exhibit HSC-selective DT sensitivity. We demonstrate robust, rapid, and highly selective cell ablation in these models. These new mouse models provide a platform to test whether HSCs are required for long-term hematopoiesis in vivo, for understanding the mechanisms regulating HSC engraftment, and interrogating in vivo hematopoietic differentiation pathways and mechanisms regulating hematopoietic homeostasis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据