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Dis Model Mech. 2018 Nov 5;11(11). pii: dmm034876. doi: 10.1242/dmm.034876.

Generation of mouse-zebrafish hematopoietic tissue chimeric embryos for hematopoiesis and host-pathogen interaction studies.

Author information

1
Center for Genome Regulation, Facultad de Ciencias, Universidad de Chile, Santiago 8370415, Chile.
2
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
3
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
4
Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
5
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
6
Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
7
Center for Systems Biology, Program in Membrane Biology, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
8
Gastrointestinal Research Group, Faculty of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada.
9
Immunology and Allergy, Department of Medicine, Solna, Karolinska Institute and University Hospital, Stockholm SE-171 76, Sweden.
10
Center for Genome Regulation, Facultad de Ciencias, Universidad de Chile, Santiago 8370415, Chile mallende@uchile.cl.
11
Department of Cell Biology and Human Anatomy, University of California, Davis, Davis, CA 95616, USA.

Abstract

Xenografts of the hematopoietic system are extremely useful as disease models and for translational research. Zebrafish xenografts have been widely used to monitor blood cancer cell dissemination and homing due to the optical clarity of embryos and larvae, which allow unrestricted in vivo visualization of migratory events. Here, we have developed a xenotransplantation technique that transiently generates hundreds of hematopoietic tissue chimeric embryos by transplanting murine bone marrow cells into zebrafish blastulae. In contrast to previous methods, this procedure allows mammalian cell integration into the fish developmental hematopoietic program, which results in chimeric animals containing distinct phenotypes of murine blood cells in both circulation and the hematopoietic niche. Murine cells in chimeric animals express antigens related to (i) hematopoietic stem and progenitor cells, (ii) active cell proliferation and (iii) myeloid cell lineages. We verified the utility of this method by monitoring zebrafish chimeras during development using in vivo non-invasive imaging to show novel murine cell behaviors, such as homing to primitive and definitive hematopoietic tissues, dynamic hematopoietic cell and hematopoietic niche interactions, and response to bacterial infection. Overall, transplantation into the zebrafish blastula provides a useful method that simplifies the generation of numerous chimeric animals and expands the range of murine cell behaviors that can be studied in zebrafish chimeras. In addition, integration of murine cells into the host hematopoietic system during development suggests highly conserved molecular mechanisms of hematopoiesis between zebrafish and mammals.This article has an associated First Person interview with the first author of the paper.

KEYWORDS:

Cell migration; Hematopoiesis; Host-pathogen interactions; Live imaging; Xenotransplantation; Zebrafish

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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