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An overlooked subse...
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Zhou, K.Karolinska Institutet
(författare)
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
- Artikel/kapitelEngelska2022
Förlag, utgivningsår, omfång ...
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2022-01-21
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Springer Science and Business Media LLC,2022
Nummerbeteckningar
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LIBRIS-ID:oai:gup.ub.gu.se/313464
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https://gup.ub.gu.se/publication/313464URI
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https://doi.org/10.1186/s12974-022-02381-6DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-466915URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:148584941URI
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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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 och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Han, J. M.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.
(författare)
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Lund, H.Karolinska Institutet
(författare)
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Boggavarapu, N. R.Karolinska Institutet
(författare)
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Lauschke, V. M.Karolinska Institutet
(författare)
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Goto, S.Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Nagoya City Univ Hosp, Dept Obstet & Gynecol, Nagoya, Aichi, Japan.
(författare)
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Cheng, H. T.Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
(författare)
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Wang, Y. Y.Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
(författare)
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Tachi, A.Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Nagoya Univ, Grad Sch Med, Dept Obstet & Gynecol, Nagoya, Aichi, Japan.
(författare)
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Xie, C. C.Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
(författare)
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Zhu, K. Y.
(författare)
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Sun, YingUppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)yisun086
(författare)
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Osman, A. M.Karolinska Institutet
(författare)
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Liang, D.Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
(författare)
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Han, W.Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
(författare)
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Gemzell-Danielsson, K.Karolinska Institutet
(författare)
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Betsholtz, ChristerUppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Dept Med Huddinge, Campus Flemingsberg, Huddinge, Sweden.(Swepub:uu)chbet517
(författare)
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Zhang, X. M.Karolinska Univ Hosp, Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci,Appl Immunol & Immunotherapy, Stockholm, Sweden.
(författare)
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Zhu, Changlian,1964Karolinska 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.(Swepub:gu)xzhuch
(författare)
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Enge, M.Karolinska Institutet
(författare)
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Joseph, B.Karolinska Institutet
(författare)
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Harris, R. A.Karolinska Institutet
(författare)
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Blomgren, K.Karolinska Institutet
(författare)
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Karolinska InstitutetKarolinska 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)
Sammanhörande titlar
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Ingår i:Journal of Neuroinflammation: Springer Science and Business Media LLC19:11742-2094
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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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