RT Journal Article
SR Electronic
T1 Generation of Mouse-Zebrafish Hematopoietic Tissue Chimeric Embryos for Hematopoiesis and Host-Pathogen Interaction Studies
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 216895
DO 10.1101/216895
A1 Margarita Parada-Kusz
A1 Anne Clatworthy
A1 Elliott J. Hagedorn
A1 Cristina Penaranda
A1 Anil V. Nair
A1 Jonathan E. Henninger
A1 Christoph Ernst
A1 Brian Li
A1 Raquel Riquelme
A1 Humberto Jijon
A1 Eduardo J. Villablanca
A1 Leonard I. Zon
A1 Deborah Hung
A1 Miguel L. Allende
YR 2017
UL http://biorxiv.org/content/early/2017/11/09/216895.abstract
AB 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. To broaden the scope of xenotransplantation studies in zebrafish, we have developed a technique that transiently generates hematopoietic tissue chimeras by transplanting murine bone marrow cells into zebrafish blastulae. This procedure leads to mammalian cell integration into the fish developmental hematopoietic program. Monitoring zebrafish chimeras at different time points post fertilization using in vivo time-lapse and confocal imaging showed murine cell co-localization with developing primitive and definitive hematopoietic tissues, intravasation into fish circulation, and dynamic hematopoietic cell-vascular endothelial and hematopoietic cell-niche interactions. Immunohistochemistry assays performed in chimeric animals showed that, after engraftment, murine cells expressed antigens related to i) hematopoietic stem and progenitor cells, ii) active cell proliferation, and iii) myeloid cell lineages. Lastly, xenografted zebrafish larvae infected with Klebsiella pneumoniae showed murine immune cells trafficking to bacterial foci and interacting with bacterial cells. Overall, these results show that mammalian bone marrow cells xenografted in zebrafish integrate into the host hematopoietic system revealing highly conserved molecular mechanisms of hematopoiesis between zebrafish and mammals. In addition, this procedure introduces a useful and simple method that improves and broadens the scope of hematopoietic tissue xenotransplantation studies in zebrafish.