Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an Immunodeficient Mouse Model with Kit Wv 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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)425-438
Number of pages14
JournalStem Cell Reports
Volume7
Issue number3
DOIs
Publication statusPublished - Sep 13 2016

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Thrombopoiesis
Erythropoiesis
Bone
Cells
Clodronic Acid
Mutation
Macrophages
Hematopoietic Stem Cells
Platelets
Heterografts
Blood
Hematopoiesis
Bone Marrow
Heterologous Transplantation
Inbred NOD Mouse
Chimerism
Fetal Blood
Blood Cells
Blood Platelets
Erythrocytes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an Immunodeficient Mouse Model with Kit Wv Mutations . / Yurino, Ayano; Takenaka, Katsuto; Yamauchi, Takuji; Nunomura, Takuya; Uehara, Yasufumi; Jinnouchi, Fumiaki; Miyawaki, Kohta; Kikushige, Yoshikane; Kato, Koji; Miyamoto, Toshihiro; Iwasaki, Hiromi; Kunisaki, Yuya; Akashi, Koichi.

In: Stem Cell Reports, Vol. 7, No. 3, 13.09.2016, p. 425-438.

Research output: Contribution to journalArticle

Yurino, Ayano ; Takenaka, Katsuto ; Yamauchi, Takuji ; Nunomura, Takuya ; Uehara, Yasufumi ; Jinnouchi, Fumiaki ; Miyawaki, Kohta ; Kikushige, Yoshikane ; Kato, Koji ; Miyamoto, Toshihiro ; Iwasaki, Hiromi ; Kunisaki, Yuya ; Akashi, Koichi. / Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an Immunodeficient Mouse Model with Kit Wv Mutations In: Stem Cell Reports. 2016 ; Vol. 7, No. 3. pp. 425-438.
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