Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells

doi:10.1126/science.abe2485

GSTDTAP > 气候变化

DOI	10.1126/science.abe2485
	Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells
	Yuanbin Song; Liang Shan; Rana Gbyli; Wei Liu; Till Strowig; Amisha Patel; Xiaoying Fu; Xiaman Wang; Mina L. Xu; Yimeng Gao; Ashley Qin; Emanuela M. Bruscia; Toma Tebaldi; Giulia Biancon; Padmavathi Mamillapalli; David Urbonas; Elizabeth Eynon; David G. Gonzalez; Jie Chen; Diane S. Krause; Jonathan Alderman; Stephanie Halene; Richard A. Flavell
	2021-03-05
发表期刊	Science
出版年	2021
英文摘要	The study of primary human red blood cell (huRBC) disorders such as sickle cell disease (SCD) and infectious diseases such as malaria has been hampered by a lack of in vivo models of human erythropoiesis. Song et al. transferred human fetal liver cells into MISTRG mice, which are immunodeficient and are genetically engineered with several human genes involved in hematopoiesis. This approach was unsuccessful because mature huRBCs are rapidly destroyed in the mouse liver. They then used CRISPR-Cas9 to mutate these mice into a fumarylacetoacetate hydrolase–deficient strain, allowing them to replace the mouse liver with engrafted human hepatocytes. These mice exhibited enhanced human erythropoiesis and circulating huRBC survival and could recapitulate SCD pathology when reconstituted with SCD-derived HSCs. Science , this issue p. [1019][1] In vivo models that recapitulate human erythropoiesis with persistence of circulating red blood cells (RBCs) have remained elusive. We report an immunodeficient murine model in which combined human liver and cytokine humanization confer enhanced human erythropoiesis and RBC survival in the circulation. We deleted the fumarylacetoacetate hydrolase ( Fah ) gene in MISTRG mice expressing several human cytokines in place of their murine counterparts. Liver humanization by intrasplenic injection of human hepatocytes (huHep) eliminated murine complement C3 and reduced murine Kupffer cell density. Engraftment of human sickle cell disease (SCD)–derived hematopoietic stem cells in huHepMISTRG Fah −/− mice resulted in vaso-occlusion that replicated acute SCD pathology. Combined liver–cytokine–humanized mice will facilitate the study of diseases afflicting RBCs, including bone marrow failure, hemoglobinopathies, and malaria, and also preclinical testing of therapies. [1]: /lookup/doi/10.1126/science.abe2485
领域	气候变化 ; 资源环境
URL	查看原文
引用统计	被引频次：20[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/316997
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Yuanbin Song,Liang Shan,Rana Gbyli,等. Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells[J]. Science,2021.
APA	Yuanbin Song.,Liang Shan.,Rana Gbyli.,Wei Liu.,Till Strowig.,...&Richard A. Flavell.(2021).Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells.Science.
MLA	Yuanbin Song,et al."Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells".Science (2021).