Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an Immunodeficient Mouse Model with KitWv Mutations

Ayano Yurino, Katsuto Takenaka, Takuji Yamauchi, Takuya Nunomura, Yasufumi Uehara, Fumiaki Jinnouchi, Kohta Miyawaki, Yoshikane Kikushige, Koji Kato, Toshihiro Miyamoto, Hiromi Iwasaki, Yuya Kunisaki, Koichi Akashi

研究成果: ジャーナルへの寄稿記事

9 引用 (Scopus)

抜粋

In human-to-mouse xenograft models, reconstitution of human hematopoiesis is usually B-lymphoid dominant. Here we show that the introduction of homozygous KitWv mutations into C57BL/6.Rag2nullIl2rgnull 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.Rag2nullIl2rgnullNOD-Sirpa KitWv/Wv (BRGSKWv/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 BRGSKWv/Wv mouse model is a useful tool to study human multi-lineage hematopoiesis.

元の言語英語
ページ(範囲)425-438
ページ数14
ジャーナルStem Cell Reports
7
発行部数3
DOI
出版物ステータス出版済み - 9 13 2016

    フィンガープリント

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

これを引用