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Fate mapping via CCR2-CreER mice reveals monocyte-to-microglia transition in development and neonatal stroke

Whether monocytes contribute to the brain microglial pool in development or after brain injury remains contentious. To address this issue, we generated CCR2-CreER mice to track monocyte derivatives in a tamoxifen-inducible manner. This method labeled Ly6C(hi) and Ly6C(lo) monocytes after tamoxifen d...

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Autores principales: Chen, Hong-Ru, Sun, Yu-Yo, Chen, Ching-Wen, Kuo, Yi-Min, Kuan, Irena S., Tiger Li, Zheng-Rong, Short-Miller, Jonah C., Smucker, Marchelle R., Kuan, Chia-Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449686/
https://www.ncbi.nlm.nih.gov/pubmed/32923636
http://dx.doi.org/10.1126/sciadv.abb2119
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author Chen, Hong-Ru
Sun, Yu-Yo
Chen, Ching-Wen
Kuo, Yi-Min
Kuan, Irena S.
Tiger Li, Zheng-Rong
Short-Miller, Jonah C.
Smucker, Marchelle R.
Kuan, Chia-Yi
author_facet Chen, Hong-Ru
Sun, Yu-Yo
Chen, Ching-Wen
Kuo, Yi-Min
Kuan, Irena S.
Tiger Li, Zheng-Rong
Short-Miller, Jonah C.
Smucker, Marchelle R.
Kuan, Chia-Yi
author_sort Chen, Hong-Ru
collection PubMed
description Whether monocytes contribute to the brain microglial pool in development or after brain injury remains contentious. To address this issue, we generated CCR2-CreER mice to track monocyte derivatives in a tamoxifen-inducible manner. This method labeled Ly6C(hi) and Ly6C(lo) monocytes after tamoxifen dosing and detected a surge of perivascular macrophages before blood-brain barrier breakdown in adult stroke. When dosed by tamoxifen at embryonic day 17 (E17), this method captured fetal hematopoietic cells at E18, subdural Ki67(+) ameboid cells at postnatal day 2 (P2), and perivascular microglia, leptomeningeal macrophages, and Iba1(+)Tmem119(+)P2RY12(+) parenchymal microglia in selective brain regions at P24. Furthermore, this fate mapping strategy revealed an acute influx of monocytes after neonatal stroke, which gradually transformed into a ramified morphology and expressed microglial marker genes (Sall1, Tmem119, and P2RY12) for at least 62 days after injury. These results suggest an underappreciated level of monocyte-to-microglia transition in development and after neonatal stroke.
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spelling pubmed-74496862020-09-11 Fate mapping via CCR2-CreER mice reveals monocyte-to-microglia transition in development and neonatal stroke Chen, Hong-Ru Sun, Yu-Yo Chen, Ching-Wen Kuo, Yi-Min Kuan, Irena S. Tiger Li, Zheng-Rong Short-Miller, Jonah C. Smucker, Marchelle R. Kuan, Chia-Yi Sci Adv Research Articles Whether monocytes contribute to the brain microglial pool in development or after brain injury remains contentious. To address this issue, we generated CCR2-CreER mice to track monocyte derivatives in a tamoxifen-inducible manner. This method labeled Ly6C(hi) and Ly6C(lo) monocytes after tamoxifen dosing and detected a surge of perivascular macrophages before blood-brain barrier breakdown in adult stroke. When dosed by tamoxifen at embryonic day 17 (E17), this method captured fetal hematopoietic cells at E18, subdural Ki67(+) ameboid cells at postnatal day 2 (P2), and perivascular microglia, leptomeningeal macrophages, and Iba1(+)Tmem119(+)P2RY12(+) parenchymal microglia in selective brain regions at P24. Furthermore, this fate mapping strategy revealed an acute influx of monocytes after neonatal stroke, which gradually transformed into a ramified morphology and expressed microglial marker genes (Sall1, Tmem119, and P2RY12) for at least 62 days after injury. These results suggest an underappreciated level of monocyte-to-microglia transition in development and after neonatal stroke. American Association for the Advancement of Science 2020-08-26 /pmc/articles/PMC7449686/ /pubmed/32923636 http://dx.doi.org/10.1126/sciadv.abb2119 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Chen, Hong-Ru
Sun, Yu-Yo
Chen, Ching-Wen
Kuo, Yi-Min
Kuan, Irena S.
Tiger Li, Zheng-Rong
Short-Miller, Jonah C.
Smucker, Marchelle R.
Kuan, Chia-Yi
Fate mapping via CCR2-CreER mice reveals monocyte-to-microglia transition in development and neonatal stroke
title Fate mapping via CCR2-CreER mice reveals monocyte-to-microglia transition in development and neonatal stroke
title_full Fate mapping via CCR2-CreER mice reveals monocyte-to-microglia transition in development and neonatal stroke
title_fullStr Fate mapping via CCR2-CreER mice reveals monocyte-to-microglia transition in development and neonatal stroke
title_full_unstemmed Fate mapping via CCR2-CreER mice reveals monocyte-to-microglia transition in development and neonatal stroke
title_short Fate mapping via CCR2-CreER mice reveals monocyte-to-microglia transition in development and neonatal stroke
title_sort fate mapping via ccr2-creer mice reveals monocyte-to-microglia transition in development and neonatal stroke
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449686/
https://www.ncbi.nlm.nih.gov/pubmed/32923636
http://dx.doi.org/10.1126/sciadv.abb2119
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