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Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an Immunodeficient Mouse Model with Kit(Wv) Mutations.

Abstract：

:In human-to-mouse xenograft models, reconstitution of human hematopoiesis is usually B-lymphoid dominant. Here we show that the introduction of homozygous Kit(Wv) mutations into C57BL/6.Rag2(null)Il2rg(null) mice with NOD-Sirpa (BRGS) strongly promoted human multi-lineage reconstitution. After xenotransplantation of human CD34(+)CD38(-) cord blood cells, these newly generated C57BL/6.Rag2(null)Il2rg(null)NOD-Sirpa Kit(Wv/Wv) (BRGSK(Wv/Wv)) mice showed significantly higher levels of human cell chimerism and long-term multi-lineage reconstitution compared with BRGS mice. Strikingly, this mouse displayed a robust reconstitution of human erythropoiesis and thrombopoiesis with terminal maturation in the bone marrow. Furthermore, depletion of host macrophages by clodronate administration resulted in the presence of human erythrocytes and platelets in the circulation. Thus, attenuation of mouse KIT signaling greatly enhances the multi-lineage differentiation of human hematopoietic stem and progenitor cells (HSPCs) in mouse bone marrow, presumably by outcompeting mouse HSPCs to occupy suitable microenvironments. The BRGSK(Wv/Wv) mouse model is a useful tool to study human multi-lineage hematopoiesis.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Yurino A,Takenaka K,Yamauchi T,Nunomura T,Uehara Y,Jinnouchi F,Miyawaki K,Kikushige Y,Kato K,Miyamoto T,Iwasaki H,Kunisaki Y,Akashi K

doi

10.1016/j.stemcr.2016.07.002

subject

Has Abstract

pub_date

2016-09-13 00:00:00

pages

425-438

issue

3

issn

2213-6711

pii

S2213-6711(16)30107-2

journal_volume

7

pub_type

杂志文章

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