Acute and endothelial-specific Robo4 deletion affect hematopoietic stem cell trafficking independent of VCAM1.

Hematopoietic stem cell (HSC) trafficking is regulated by a number of complex mechanisms. Among them are the transmembrane protein Robo4 and the vascular cell adhesion molecule, VCAM1. Endothelial VCAM1 is a well-known regulator of hematopoietic cell trafficking, and our previous studies revealed th...

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Autores principales:	Stephanie Smith-Berdan, Alyssa Bercasio, Leah Kramer, Bryan Petkus, Lindsay Hinck, E Camilla Forsberg
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aa8e84cb503749c6b5b8735fb583684a
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spelling	oai:doaj.org-article:aa8e84cb503749c6b5b8735fb583684a2021-12-02T20:18:12ZAcute and endothelial-specific Robo4 deletion affect hematopoietic stem cell trafficking independent of VCAM1.1932-620310.1371/journal.pone.0255606https://doaj.org/article/aa8e84cb503749c6b5b8735fb583684a2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0255606https://doaj.org/toc/1932-6203Hematopoietic stem cell (HSC) trafficking is regulated by a number of complex mechanisms. Among them are the transmembrane protein Robo4 and the vascular cell adhesion molecule, VCAM1. Endothelial VCAM1 is a well-known regulator of hematopoietic cell trafficking, and our previous studies revealed that germline deletion of Robo4 led to impaired HSC trafficking, with an increase in vascular endothelial cell (VEC) numbers and downregulation of VCAM1 protein on sinusoidal VECs. Here, we utilized two Robo4 conditional deletion models in parallel with Robo4 germline knockout mice (R4KO) to evaluate the effects of acute and endothelial cell-specific Robo4 deletion on HSC trafficking. Strikingly similar to the R4KO, the acute deletion of Robo4 resulted in altered HSC distribution between the bone marrow and blood compartments, despite normal numbers of VECs and wild-type levels of VCAM1 cell surface protein on sinusoidal VECs. Additionally, consistent with the R4KO mice, acute loss of Robo4 in the host perturbed long-term engraftment of donor wild-type HSCs and improved HSC mobilization to the peripheral blood. These data demonstrate the significant role that endothelial Robo4 plays in directional HSC trafficking, independent of alterations in VEC numbers and VCAM1 expression.Stephanie Smith-BerdanAlyssa BercasioLeah KramerBryan PetkusLindsay HinckE Camilla ForsbergPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0255606 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stephanie Smith-Berdan Alyssa Bercasio Leah Kramer Bryan Petkus Lindsay Hinck E Camilla Forsberg Acute and endothelial-specific Robo4 deletion affect hematopoietic stem cell trafficking independent of VCAM1.
description	Hematopoietic stem cell (HSC) trafficking is regulated by a number of complex mechanisms. Among them are the transmembrane protein Robo4 and the vascular cell adhesion molecule, VCAM1. Endothelial VCAM1 is a well-known regulator of hematopoietic cell trafficking, and our previous studies revealed that germline deletion of Robo4 led to impaired HSC trafficking, with an increase in vascular endothelial cell (VEC) numbers and downregulation of VCAM1 protein on sinusoidal VECs. Here, we utilized two Robo4 conditional deletion models in parallel with Robo4 germline knockout mice (R4KO) to evaluate the effects of acute and endothelial cell-specific Robo4 deletion on HSC trafficking. Strikingly similar to the R4KO, the acute deletion of Robo4 resulted in altered HSC distribution between the bone marrow and blood compartments, despite normal numbers of VECs and wild-type levels of VCAM1 cell surface protein on sinusoidal VECs. Additionally, consistent with the R4KO mice, acute loss of Robo4 in the host perturbed long-term engraftment of donor wild-type HSCs and improved HSC mobilization to the peripheral blood. These data demonstrate the significant role that endothelial Robo4 plays in directional HSC trafficking, independent of alterations in VEC numbers and VCAM1 expression.
format	article
author	Stephanie Smith-Berdan Alyssa Bercasio Leah Kramer Bryan Petkus Lindsay Hinck E Camilla Forsberg
author_facet	Stephanie Smith-Berdan Alyssa Bercasio Leah Kramer Bryan Petkus Lindsay Hinck E Camilla Forsberg
author_sort	Stephanie Smith-Berdan
title	Acute and endothelial-specific Robo4 deletion affect hematopoietic stem cell trafficking independent of VCAM1.
title_short	Acute and endothelial-specific Robo4 deletion affect hematopoietic stem cell trafficking independent of VCAM1.
title_full	Acute and endothelial-specific Robo4 deletion affect hematopoietic stem cell trafficking independent of VCAM1.
title_fullStr	Acute and endothelial-specific Robo4 deletion affect hematopoietic stem cell trafficking independent of VCAM1.
title_full_unstemmed	Acute and endothelial-specific Robo4 deletion affect hematopoietic stem cell trafficking independent of VCAM1.
title_sort	acute and endothelial-specific robo4 deletion affect hematopoietic stem cell trafficking independent of vcam1.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/aa8e84cb503749c6b5b8735fb583684a
work_keys_str_mv	AT stephaniesmithberdan acuteandendothelialspecificrobo4deletionaffecthematopoieticstemcelltraffickingindependentofvcam1 AT alyssabercasio acuteandendothelialspecificrobo4deletionaffecthematopoieticstemcelltraffickingindependentofvcam1 AT leahkramer acuteandendothelialspecificrobo4deletionaffecthematopoieticstemcelltraffickingindependentofvcam1 AT bryanpetkus acuteandendothelialspecificrobo4deletionaffecthematopoieticstemcelltraffickingindependentofvcam1 AT lindsayhinck acuteandendothelialspecificrobo4deletionaffecthematopoieticstemcelltraffickingindependentofvcam1 AT ecamillaforsberg acuteandendothelialspecificrobo4deletionaffecthematopoieticstemcelltraffickingindependentofvcam1
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Acute and endothelial-specific Robo4 deletion affect hematopoietic stem cell trafficking independent of VCAM1.

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