Engraftment, Fate, and Function of HoxB8-Conditional Neutrophil Progenitors in the Unconditioned Murine Host

The development and use of murine myeloid progenitor cell lines that are conditionally immortalized through expression of HoxB8 has provided a valuable tool for studies of neutrophil biology. Recent work has extended the utility of HoxB8-conditional progenitors to the in vivo setting via their trans...

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Main Authors: Joshua T. Cohen, Michael Danise, Kristina D. Hinman, Brittany M. Neumann, Renita Johnson, Zachary S. Wilson, Anna Chorzalska, Patrycja M. Dubielecka, Craig T. Lefort
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2022.840894/full
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author Joshua T. Cohen
Michael Danise
Kristina D. Hinman
Kristina D. Hinman
Brittany M. Neumann
Renita Johnson
Zachary S. Wilson
Zachary S. Wilson
Anna Chorzalska
Patrycja M. Dubielecka
Craig T. Lefort
author_facet Joshua T. Cohen
Michael Danise
Kristina D. Hinman
Kristina D. Hinman
Brittany M. Neumann
Renita Johnson
Zachary S. Wilson
Zachary S. Wilson
Anna Chorzalska
Patrycja M. Dubielecka
Craig T. Lefort
author_sort Joshua T. Cohen
collection DOAJ
description The development and use of murine myeloid progenitor cell lines that are conditionally immortalized through expression of HoxB8 has provided a valuable tool for studies of neutrophil biology. Recent work has extended the utility of HoxB8-conditional progenitors to the in vivo setting via their transplantation into irradiated mice. Here, we describe the isolation of HoxB8-conditional progenitor cell lines that are unique in their ability to engraft in the naïve host in the absence of conditioning of the hematopoietic niche. Our results indicate that HoxB8-conditional progenitors engraft in a β1 integrin-dependent manner and transiently generate donor-derived mature neutrophils. Furthermore, we show that neutrophils derived in vivo from transplanted HoxB8-conditional progenitors are mobilized to the periphery and recruited to sites of inflammation in a manner that depends on the C-X-C chemokine receptor 2 and β2 integrins, the same mechanisms that have been described for recruitment of endogenous primary neutrophils. Together, our studies advance the understanding of HoxB8-conditional neutrophil progenitors and describe an innovative tool that, by virtue of its ability to engraft in the naïve host, will facilitate mechanistic in vivo experimentation on neutrophils.
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spelling doaj.art-de82f9ec28bc4ac29f9113161ed126b52022-12-22T04:16:04ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-01-011010.3389/fcell.2022.840894840894Engraftment, Fate, and Function of HoxB8-Conditional Neutrophil Progenitors in the Unconditioned Murine HostJoshua T. Cohen0Michael Danise1Kristina D. Hinman2Kristina D. Hinman3Brittany M. Neumann4Renita Johnson5Zachary S. Wilson6Zachary S. Wilson7Anna Chorzalska8Patrycja M. Dubielecka9Craig T. Lefort10Division of Surgical Research, Department of Surgery, Rhode Island Hospital, Providence, RI, United StatesDivision of Surgical Research, Department of Surgery, Rhode Island Hospital, Providence, RI, United StatesDivision of Surgical Research, Department of Surgery, Rhode Island Hospital, Providence, RI, United StatesGraduate Program in Pathobiology, Brown University, Providence, RI, United StatesDivision of Surgical Research, Department of Surgery, Rhode Island Hospital, Providence, RI, United StatesDivision of Surgical Research, Department of Surgery, Rhode Island Hospital, Providence, RI, United StatesDivision of Surgical Research, Department of Surgery, Rhode Island Hospital, Providence, RI, United StatesGraduate Program in Pathobiology, Brown University, Providence, RI, United StatesDivision of Hematology/Oncology, Rhode Island Hospital, Providence, RI, United StatesDivision of Hematology/Oncology, Rhode Island Hospital, Providence, RI, United StatesDivision of Surgical Research, Department of Surgery, Rhode Island Hospital, Providence, RI, United StatesThe development and use of murine myeloid progenitor cell lines that are conditionally immortalized through expression of HoxB8 has provided a valuable tool for studies of neutrophil biology. Recent work has extended the utility of HoxB8-conditional progenitors to the in vivo setting via their transplantation into irradiated mice. Here, we describe the isolation of HoxB8-conditional progenitor cell lines that are unique in their ability to engraft in the naïve host in the absence of conditioning of the hematopoietic niche. Our results indicate that HoxB8-conditional progenitors engraft in a β1 integrin-dependent manner and transiently generate donor-derived mature neutrophils. Furthermore, we show that neutrophils derived in vivo from transplanted HoxB8-conditional progenitors are mobilized to the periphery and recruited to sites of inflammation in a manner that depends on the C-X-C chemokine receptor 2 and β2 integrins, the same mechanisms that have been described for recruitment of endogenous primary neutrophils. Together, our studies advance the understanding of HoxB8-conditional neutrophil progenitors and describe an innovative tool that, by virtue of its ability to engraft in the naïve host, will facilitate mechanistic in vivo experimentation on neutrophils.https://www.frontiersin.org/articles/10.3389/fcell.2022.840894/fullneutrophilshematopoietic stem and progenitor cell (HSPC)engraftmentgranulopoeisiscell therapeuticsleukocyte recruitment
spellingShingle Joshua T. Cohen
Michael Danise
Kristina D. Hinman
Kristina D. Hinman
Brittany M. Neumann
Renita Johnson
Zachary S. Wilson
Zachary S. Wilson
Anna Chorzalska
Patrycja M. Dubielecka
Craig T. Lefort
Engraftment, Fate, and Function of HoxB8-Conditional Neutrophil Progenitors in the Unconditioned Murine Host
Frontiers in Cell and Developmental Biology
neutrophils
hematopoietic stem and progenitor cell (HSPC)
engraftment
granulopoeisis
cell therapeutics
leukocyte recruitment
title Engraftment, Fate, and Function of HoxB8-Conditional Neutrophil Progenitors in the Unconditioned Murine Host
title_full Engraftment, Fate, and Function of HoxB8-Conditional Neutrophil Progenitors in the Unconditioned Murine Host
title_fullStr Engraftment, Fate, and Function of HoxB8-Conditional Neutrophil Progenitors in the Unconditioned Murine Host
title_full_unstemmed Engraftment, Fate, and Function of HoxB8-Conditional Neutrophil Progenitors in the Unconditioned Murine Host
title_short Engraftment, Fate, and Function of HoxB8-Conditional Neutrophil Progenitors in the Unconditioned Murine Host
title_sort engraftment fate and function of hoxb8 conditional neutrophil progenitors in the unconditioned murine host
topic neutrophils
hematopoietic stem and progenitor cell (HSPC)
engraftment
granulopoeisis
cell therapeutics
leukocyte recruitment
url https://www.frontiersin.org/articles/10.3389/fcell.2022.840894/full
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