Generation of reconstituted hemato-lymphoid murine embryos by placental transplantation into embryos lacking HSCs

Abstract In order to increase the contribution of donor HSC cells, irradiation and DNA alkylating agents have been commonly used as experimental methods to eliminate HSCs for adult mice. But a technique of HSC deletion for mouse embryo for increase contribution of donor cells has not been published....

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Autores principales: Hyojung Jeon, Keigo Asano, Arata Wakimoto, Kaushalya Kulathunga, Mai Thi Nhu Tran, Megumi Nakamura, Tomomasa Yokomizo, Michito Hamada, Satoru Takahashi
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/98c72039521d4ef6b1e5ffbb80d0d82b
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spelling oai:doaj.org-article:98c72039521d4ef6b1e5ffbb80d0d82b2021-12-02T14:28:17ZGeneration of reconstituted hemato-lymphoid murine embryos by placental transplantation into embryos lacking HSCs10.1038/s41598-021-83652-92045-2322https://doaj.org/article/98c72039521d4ef6b1e5ffbb80d0d82b2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83652-9https://doaj.org/toc/2045-2322Abstract In order to increase the contribution of donor HSC cells, irradiation and DNA alkylating agents have been commonly used as experimental methods to eliminate HSCs for adult mice. But a technique of HSC deletion for mouse embryo for increase contribution of donor cells has not been published. Here, we established for the first time a procedure for placental HSC transplantation into E11.5 Runx1-deficient mice mated with G1-HRD-Runx1 transgenic mice (Runx1 -/- ::Tg mice) that have no HSCs in the fetal liver. Following the transplantation of fetal liver cells from mice (allogeneic) or rats (xenogeneic), high donor cell chimerism was observed in Runx1 -/- ::Tg embryos. Furthermore, chimerism analysis and colony assay data showed that donor fetal liver hematopoietic cells contributed to both white blood cells and red blood cells. Moreover, secondary transplantation into adult recipient mice indicated that the HSCs in rescued Runx1 -/- ::Tg embryos had normal abilities. These results suggest that mice lacking fetal liver HSCs are a powerful tool for hematopoiesis reconstruction during the embryonic stage and can potentially be used in basic research on HSCs or xenograft models.Hyojung JeonKeigo AsanoArata WakimotoKaushalya KulathungaMai Thi Nhu TranMegumi NakamuraTomomasa YokomizoMichito HamadaSatoru TakahashiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Hyojung Jeon
Keigo Asano
Arata Wakimoto
Kaushalya Kulathunga
Mai Thi Nhu Tran
Megumi Nakamura
Tomomasa Yokomizo
Michito Hamada
Satoru Takahashi
Generation of reconstituted hemato-lymphoid murine embryos by placental transplantation into embryos lacking HSCs
description Abstract In order to increase the contribution of donor HSC cells, irradiation and DNA alkylating agents have been commonly used as experimental methods to eliminate HSCs for adult mice. But a technique of HSC deletion for mouse embryo for increase contribution of donor cells has not been published. Here, we established for the first time a procedure for placental HSC transplantation into E11.5 Runx1-deficient mice mated with G1-HRD-Runx1 transgenic mice (Runx1 -/- ::Tg mice) that have no HSCs in the fetal liver. Following the transplantation of fetal liver cells from mice (allogeneic) or rats (xenogeneic), high donor cell chimerism was observed in Runx1 -/- ::Tg embryos. Furthermore, chimerism analysis and colony assay data showed that donor fetal liver hematopoietic cells contributed to both white blood cells and red blood cells. Moreover, secondary transplantation into adult recipient mice indicated that the HSCs in rescued Runx1 -/- ::Tg embryos had normal abilities. These results suggest that mice lacking fetal liver HSCs are a powerful tool for hematopoiesis reconstruction during the embryonic stage and can potentially be used in basic research on HSCs or xenograft models.
format article
author Hyojung Jeon
Keigo Asano
Arata Wakimoto
Kaushalya Kulathunga
Mai Thi Nhu Tran
Megumi Nakamura
Tomomasa Yokomizo
Michito Hamada
Satoru Takahashi
author_facet Hyojung Jeon
Keigo Asano
Arata Wakimoto
Kaushalya Kulathunga
Mai Thi Nhu Tran
Megumi Nakamura
Tomomasa Yokomizo
Michito Hamada
Satoru Takahashi
author_sort Hyojung Jeon
title Generation of reconstituted hemato-lymphoid murine embryos by placental transplantation into embryos lacking HSCs
title_short Generation of reconstituted hemato-lymphoid murine embryos by placental transplantation into embryos lacking HSCs
title_full Generation of reconstituted hemato-lymphoid murine embryos by placental transplantation into embryos lacking HSCs
title_fullStr Generation of reconstituted hemato-lymphoid murine embryos by placental transplantation into embryos lacking HSCs
title_full_unstemmed Generation of reconstituted hemato-lymphoid murine embryos by placental transplantation into embryos lacking HSCs
title_sort generation of reconstituted hemato-lymphoid murine embryos by placental transplantation into embryos lacking hscs
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/98c72039521d4ef6b1e5ffbb80d0d82b
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