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An overlooked subse...
An overlooked subset of Cx3cr1(wt/wt) microglia in the Cx3cr1(CreER-Eyfp/wt) mouse has a repopulation advantage over Cx3cr1(CreER-Eyfp/wt) microglia following microglial depletion
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- Zhou, K. (författare)
- Karolinska Institutet
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- Han, J. M. (författare)
- Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci,Appl Immunol & Immunotherapy, Stockholm, Sweden.;Capital Med Univ, Natl Ctr Neurol Disorders, Xuanwu Hosp, Neuroimmunol Ctr,Dept Neurol, Beijing, Peoples R China.
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- Lund, H. (författare)
- Karolinska Institutet
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- Boggavarapu, N. R. (författare)
- Karolinska Institutet
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- Lauschke, V. M. (författare)
- Karolinska Institutet
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- Goto, S. (författare)
- Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Nagoya City Univ Hosp, Dept Obstet & Gynecol, Nagoya, Aichi, Japan.
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- Cheng, H. T. (författare)
- Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
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- Wang, Y. Y. (författare)
- Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
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- Tachi, A. (författare)
- Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Nagoya Univ, Grad Sch Med, Dept Obstet & Gynecol, Nagoya, Aichi, Japan.
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- Xie, C. C. (författare)
- Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
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Zhu, K. Y. (författare)
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- Sun, Ying (författare)
- Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab
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- Osman, A. M. (författare)
- Karolinska Institutet
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- Liang, D. (författare)
- Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
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- Han, W. (författare)
- Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
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- Gemzell-Danielsson, K. (författare)
- Karolinska Institutet
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- Betsholtz, Christer (författare)
- Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Dept Med Huddinge, Campus Flemingsberg, Huddinge, Sweden.
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- Zhang, X. M. (författare)
- Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci,Appl Immunol & Immunotherapy, Stockholm, Sweden.
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- Zhu, Changlian, 1964 (författare)
- Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,Univ Gothenburg, Inst Neurosci & Physiol, Ctr Brain Repair & Rehabil, Gothenburg, Sweden.;Zhengzhou Univ, Affiliated Hosp 3, Henan Key Lab Child Brain Injury, Zhengzhou, Peoples R China.;Zhengzhou Univ, Affiliated Hosp 3, Henan Pediat Clin Res Ctr, Zhengzhou, Peoples R China.;Zhengzhou Univ, Inst Neurosci, Zhengzhou, Peoples R China.
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- Enge, M. (författare)
- Karolinska Institutet
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- Joseph, B. (författare)
- Karolinska Institutet
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- Harris, R. A. (författare)
- Karolinska Institutet
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- Blomgren, K. (författare)
- Karolinska Institutet
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Karolinska Institutet Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci,Appl Immunol & Immunotherapy, Stockholm, Sweden;Capital Med Univ, Natl Ctr Neurol Disorders, Xuanwu Hosp, Neuroimmunol Ctr,Dept Neurol, Beijing, Peoples R China. (creator_code:org_t)
- 2022-01-21
- 2022
- Engelska.
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 19:1
- Relaterad länk:
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https://jneuroinflam...
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Background Fluorescent reporter labeling and promoter-driven Cre-recombinant technologies have facilitated cellular investigations of physiological and pathological processes, including the widespread use of the Cx3cr1(CreER-Eyfp/wt) mouse strain for studies of microglia. Methods Immunohistochemistry, Flow Cytometry, RNA sequencing and whole-genome sequencing were used to identify the subpopulation of microglia in Cx3cr1(CreER-Eyfp/wt) mouse brains. Genetically mediated microglia depletion using Cx3cr1(CreER-Eyfp/wt)Rosa26(DTA/wt) mice and CSF1 receptor inhibitor PLX3397 were used to deplete microglia. Primary microglia proliferation and migration assay were used for in vitro studies. Results We unexpectedly identified a subpopulation of microglia devoid of genetic modification, exhibiting higher Cx3cr1 and CX3CR1 expression than Cx3cr1(CreER-Eyfp/wt)Cre(+)Eyfp(+) microglia in Cx3cr1(CreER-Eyfp/wt) mouse brains, thus termed Cx3cr1(high)Cre(-)Eyfp(-) microglia. This subpopulation constituted less than 1% of all microglia under homeostatic conditions, but after Cre-driven DTA-mediated microglial depletion, Cx3cr1(high)Cre(-)Eyfp(-) microglia escaped depletion and proliferated extensively, eventually occupying one-third of the total microglial pool. We further demonstrated that the Cx3cr1(high)Cre(-)Eyfp(-) microglia had lost their genetic heterozygosity and become homozygous for wild-type Cx3cr1. Therefore, Cx3cr1(high)Cre(-)Eyfp(-) microglia are Cx3cr1(wt/wt)Cre(-)Eyfp(-). Finally, we demonstrated that CX3CL1-CX3CR1 signaling regulates microglial repopulation both in vivo and in vitro. Conclusions Our results raise a cautionary note regarding the use of Cx3cr1(CreER-Eyfp/wt) mouse strains, particularly when interpreting the results of fate mapping, and microglial depletion and repopulation studies.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Microglia
- Cre
- GFP
- YFP
- Cx3cr1
- Microglial depletion
- Microglial
- repopulation
- Diphtheria toxin subunit A (DTA)
- Loss of heterozygosity
- (LOH)
- Homologous recombination
- mitotic recombination
- targeting microglia
- brain-development
- yolk-sac
- reveals
- cell
- maintenance
- macrophages
- fractalkine
- activation
- Immunology
- Neurosciences & Neurology
- Microglia
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Zhou, K.
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Han, J. M.
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Lund, H.
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Boggavarapu, N. ...
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Lauschke, V. M.
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Goto, S.
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visa fler...
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Cheng, H. T.
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Wang, Y. Y.
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Tachi, A.
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Xie, C. C.
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Zhu, K. Y.
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Sun, Ying
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Osman, A. M.
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Liang, D.
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Han, W.
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Gemzell-Danielss ...
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Betsholtz, Chris ...
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Zhang, X. M.
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Zhu, Changlian, ...
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Enge, M.
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Joseph, B.
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Harris, R. A.
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Blomgren, K.
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
- Artiklar i publikationen
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Journal of Neuro ...
- Av lärosätet
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Göteborgs universitet
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Uppsala universitet
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Karolinska Institutet