Effective expansion of engrafted human hematopoietic stem cells in bone marrow of mice expressing human Jagged1

Naoko Negishi, Daisuke Suzuki, Ryoji Ito, Naoko Irie, Koichi Matsuo, Takashi Yahata, Kenichi Nagano, Kazuhiro Aoki, Keiichi Ohya, Katsuto Hozumi, Kiyoshi Ando, Norikazu Tamaoki, Mamoru Ito, Sonoko Habu

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The human immune system can be reconstituted in experimental animals by transplanting human hematopoietic stem cells (hHSCs) into immunodeficient mice. To generate such humanized mice, further improvements are required, particularly to ensure that transplanted hHSCs are maintained in mice and proliferate long enough to follow prolonged immune responses to chronic diseases or monitor therapeutic effects. To prepare the relatively human bone marrow environment in mice, we generated nonobese diabetic/severe combined immunodeficiency/interleukin-2 receptor gamma chain null (NOG) mice expressing human Jagged1 (hJ1) in an osteoblast-specific manner (hJ1-NOG mice) to examine whether Notch signaling induced by hJ1 mediates hHSC proliferation and/or maintenance in mice. The established hJ1-NOG mice possess relatively larger bone marrow space and thinner cortical bone compared with nontransgenic littermates, but the number of c-kit+ Sca-1+ lineage- cells was not significantly different between hJ1-NOG and nontransgenic littermates. In the transplantation experiments of CD34+ cells obtained from human cord blood, CD34+CD38- cells (hHSCs) were more increased in hJ1-NOG recipient mice than in nontransgenic littermates in mouse bone marrow environment. In contrast, the transplanted mouse c-kit+ Sca-1+ lineage- cells did not show significant increase in the same hJ1-NOG mice. These results suggest that hJ1-NOG mice could contribute to the growth of transplanted human CD34+cells in a human-specific manner and be useful to study the invivo behavior and/or development of human stem cells, including cancer stem cells and immune cells.

Original languageEnglish
JournalExperimental Hematology
Volume42
Issue number6
DOIs
Publication statusPublished - 2014

Fingerprint

Hematopoietic Stem Cells
Bone Marrow
Interleukin Receptor Common gamma Subunit
Wiskott-Aldrich Syndrome
Severe Combined Immunodeficiency
Inbred NOD Mouse
Neoplastic Stem Cells
Human Development
Therapeutic Uses
Osteoblasts
Fetal Blood

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Hematology

Cite this

Effective expansion of engrafted human hematopoietic stem cells in bone marrow of mice expressing human Jagged1. / Negishi, Naoko; Suzuki, Daisuke; Ito, Ryoji; Irie, Naoko; Matsuo, Koichi; Yahata, Takashi; Nagano, Kenichi; Aoki, Kazuhiro; Ohya, Keiichi; Hozumi, Katsuto; Ando, Kiyoshi; Tamaoki, Norikazu; Ito, Mamoru; Habu, Sonoko.

In: Experimental Hematology, Vol. 42, No. 6, 2014.

Research output: Contribution to journalArticle

Negishi, N, Suzuki, D, Ito, R, Irie, N, Matsuo, K, Yahata, T, Nagano, K, Aoki, K, Ohya, K, Hozumi, K, Ando, K, Tamaoki, N, Ito, M & Habu, S 2014, 'Effective expansion of engrafted human hematopoietic stem cells in bone marrow of mice expressing human Jagged1', Experimental Hematology, vol. 42, no. 6. https://doi.org/10.1016/j.exphem.2014.02.001
Negishi, Naoko ; Suzuki, Daisuke ; Ito, Ryoji ; Irie, Naoko ; Matsuo, Koichi ; Yahata, Takashi ; Nagano, Kenichi ; Aoki, Kazuhiro ; Ohya, Keiichi ; Hozumi, Katsuto ; Ando, Kiyoshi ; Tamaoki, Norikazu ; Ito, Mamoru ; Habu, Sonoko. / Effective expansion of engrafted human hematopoietic stem cells in bone marrow of mice expressing human Jagged1. In: Experimental Hematology. 2014 ; Vol. 42, No. 6.
@article{cc39c8b0e13a447ab015d8df859b5baf,
title = "Effective expansion of engrafted human hematopoietic stem cells in bone marrow of mice expressing human Jagged1",
abstract = "The human immune system can be reconstituted in experimental animals by transplanting human hematopoietic stem cells (hHSCs) into immunodeficient mice. To generate such humanized mice, further improvements are required, particularly to ensure that transplanted hHSCs are maintained in mice and proliferate long enough to follow prolonged immune responses to chronic diseases or monitor therapeutic effects. To prepare the relatively human bone marrow environment in mice, we generated nonobese diabetic/severe combined immunodeficiency/interleukin-2 receptor gamma chain null (NOG) mice expressing human Jagged1 (hJ1) in an osteoblast-specific manner (hJ1-NOG mice) to examine whether Notch signaling induced by hJ1 mediates hHSC proliferation and/or maintenance in mice. The established hJ1-NOG mice possess relatively larger bone marrow space and thinner cortical bone compared with nontransgenic littermates, but the number of c-kit+ Sca-1+ lineage- cells was not significantly different between hJ1-NOG and nontransgenic littermates. In the transplantation experiments of CD34+ cells obtained from human cord blood, CD34+CD38- cells (hHSCs) were more increased in hJ1-NOG recipient mice than in nontransgenic littermates in mouse bone marrow environment. In contrast, the transplanted mouse c-kit+ Sca-1+ lineage- cells did not show significant increase in the same hJ1-NOG mice. These results suggest that hJ1-NOG mice could contribute to the growth of transplanted human CD34+cells in a human-specific manner and be useful to study the invivo behavior and/or development of human stem cells, including cancer stem cells and immune cells.",
author = "Naoko Negishi and Daisuke Suzuki and Ryoji Ito and Naoko Irie and Koichi Matsuo and Takashi Yahata and Kenichi Nagano and Kazuhiro Aoki and Keiichi Ohya and Katsuto Hozumi and Kiyoshi Ando and Norikazu Tamaoki and Mamoru Ito and Sonoko Habu",
year = "2014",
doi = "10.1016/j.exphem.2014.02.001",
language = "English",
volume = "42",
journal = "Experimental Hematology",
issn = "0301-472X",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Effective expansion of engrafted human hematopoietic stem cells in bone marrow of mice expressing human Jagged1

AU - Negishi, Naoko

AU - Suzuki, Daisuke

AU - Ito, Ryoji

AU - Irie, Naoko

AU - Matsuo, Koichi

AU - Yahata, Takashi

AU - Nagano, Kenichi

AU - Aoki, Kazuhiro

AU - Ohya, Keiichi

AU - Hozumi, Katsuto

AU - Ando, Kiyoshi

AU - Tamaoki, Norikazu

AU - Ito, Mamoru

AU - Habu, Sonoko

PY - 2014

Y1 - 2014

N2 - The human immune system can be reconstituted in experimental animals by transplanting human hematopoietic stem cells (hHSCs) into immunodeficient mice. To generate such humanized mice, further improvements are required, particularly to ensure that transplanted hHSCs are maintained in mice and proliferate long enough to follow prolonged immune responses to chronic diseases or monitor therapeutic effects. To prepare the relatively human bone marrow environment in mice, we generated nonobese diabetic/severe combined immunodeficiency/interleukin-2 receptor gamma chain null (NOG) mice expressing human Jagged1 (hJ1) in an osteoblast-specific manner (hJ1-NOG mice) to examine whether Notch signaling induced by hJ1 mediates hHSC proliferation and/or maintenance in mice. The established hJ1-NOG mice possess relatively larger bone marrow space and thinner cortical bone compared with nontransgenic littermates, but the number of c-kit+ Sca-1+ lineage- cells was not significantly different between hJ1-NOG and nontransgenic littermates. In the transplantation experiments of CD34+ cells obtained from human cord blood, CD34+CD38- cells (hHSCs) were more increased in hJ1-NOG recipient mice than in nontransgenic littermates in mouse bone marrow environment. In contrast, the transplanted mouse c-kit+ Sca-1+ lineage- cells did not show significant increase in the same hJ1-NOG mice. These results suggest that hJ1-NOG mice could contribute to the growth of transplanted human CD34+cells in a human-specific manner and be useful to study the invivo behavior and/or development of human stem cells, including cancer stem cells and immune cells.

AB - The human immune system can be reconstituted in experimental animals by transplanting human hematopoietic stem cells (hHSCs) into immunodeficient mice. To generate such humanized mice, further improvements are required, particularly to ensure that transplanted hHSCs are maintained in mice and proliferate long enough to follow prolonged immune responses to chronic diseases or monitor therapeutic effects. To prepare the relatively human bone marrow environment in mice, we generated nonobese diabetic/severe combined immunodeficiency/interleukin-2 receptor gamma chain null (NOG) mice expressing human Jagged1 (hJ1) in an osteoblast-specific manner (hJ1-NOG mice) to examine whether Notch signaling induced by hJ1 mediates hHSC proliferation and/or maintenance in mice. The established hJ1-NOG mice possess relatively larger bone marrow space and thinner cortical bone compared with nontransgenic littermates, but the number of c-kit+ Sca-1+ lineage- cells was not significantly different between hJ1-NOG and nontransgenic littermates. In the transplantation experiments of CD34+ cells obtained from human cord blood, CD34+CD38- cells (hHSCs) were more increased in hJ1-NOG recipient mice than in nontransgenic littermates in mouse bone marrow environment. In contrast, the transplanted mouse c-kit+ Sca-1+ lineage- cells did not show significant increase in the same hJ1-NOG mice. These results suggest that hJ1-NOG mice could contribute to the growth of transplanted human CD34+cells in a human-specific manner and be useful to study the invivo behavior and/or development of human stem cells, including cancer stem cells and immune cells.

UR - http://www.scopus.com/inward/record.url?scp=84902658803&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902658803&partnerID=8YFLogxK

U2 - 10.1016/j.exphem.2014.02.001

DO - 10.1016/j.exphem.2014.02.001

M3 - Article

C2 - 24530466

AN - SCOPUS:84902658803

VL - 42

JO - Experimental Hematology

JF - Experimental Hematology

SN - 0301-472X

IS - 6

ER -