CoChat
Sign Up
Cited by 15Neuroinflammation and Neurodegeneration MechanismsNeurogenesis and neuroplasticity mechanismsBrain Metastases and Treatment

Tmem119 expression is downregulated in a subset of brain metastasis-associated microglia

Open access
Ma, Weili, Oswald, Jack, Rios Angulo, Angela, Chen, Qing·2024·BMC Neuroscience
DOI 10.1186/s12868-024-00846-3PMC PMC10837931
Open this paper in CoChat — free accountOpen PDF

Abstract

Under pathological conditions, the immune-specialized brain microenvironment contains both resident microglia and bone marrow-derived myeloid cells recruited from peripheral circulation. Due to largely overlapping phenotypic similarities between these ontogenically distinct myeloid populations, studying their individual functions in central nervous system diseases has been challenging. Recently, transmembrane protein 119 (Tmem119) has been reported as a marker for resident microglia which is not expressed by bone marrow-derived myeloid cells. However, several studies have reported the loss or reduction of Tmem119 expression in pathologically activated microglia. Here, we examined whether Tmem119 could be used as a robust marker to identify brain metastasis-associated microglia. In addition, we also compared Tmem119 expression of primary microglia to the immortalized microglia-like BV2 cell line and characterized expression changes after LPS treatment. Lastly, we used a commercially available transgenic mouse line (Tmem119-eGFP) to compare Tmem119 expression patterns to the traditional antibody-based detection methods. Our results indicate that brain metastasis-associated microglia have reduced Tmem119 gene and protein expression.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s12868-024-00846-3

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Tmem119 expression is significantly reduced in activated microglia in AD.

    “For instance, Tmem119 expression is significantly reduced in activated microglia in AD, whereas C1qa is associated with microglial activation after traumatic brain injury[49–51].”

    From Comparative analysis of nuclei isolation methods for brain single-nucleus RNA sequencing (2026) · cites this paper as [51]

    The Results section reports significantly reduced Tmem119 expression in microglia activated by LPS, and the Discussion reports a reduction in brain metastasis-associated microglia. The Background says TMEM119 was detected in post-mortem Alzheimer’s disease samples, but the paper does not establish a significant reduction in activated microglia in AD. Page numbers are unavailable in our copy. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • C1qa is associated with microglial activation after traumatic brain injury.

    “For instance, Tmem119 expression is significantly reduced in activated microglia in AD, whereas C1qa is associated with microglial activation after traumatic brain injury[49–51].”

    From Comparative analysis of nuclei isolation methods for brain single-nucleus RNA sequencing (2026) · cites this paper as [51]

    The Background discusses TMEM119 detection in traumatic brain injury, and the Discussion links loss of Tmem119 to microglial activation. A search for C1qa found no passage connecting it to microglial activation after traumatic brain injury in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 41

  1. [1]Kim SU de Vellis J Microglia in health and disease J Neurosci Res 2005 81 3 302 13 10.1002/jnr.20562 15954124 · DOI
  2. [2]Li Q, Barres BA. Microglia and macrophages in brain homeostasis and disease. Nat Rev Immunol. 2018;18(4):225– 42. Epub 20171120. 10.1038/nri.2017.125. PubMed PMID: 29151590. 29151590 · DOI · Paper page
  3. [3]Quail DF Joyce JA The Microenvironmental Landscape of Brain tumors Cancer Cell 2017 31 3 326 41 10.1016/j.ccell.2017.02.009 28292436 PMC5424263 · DOI
  4. [4]Klemm F Maas RR Bowman RL Kornete M Soukup K Nassiri S Brouland JP Iacobuzio-Donahue CA Brennan C Tabar V Gutin PH Daniel RT Hegi ME Joyce JA Interrogation of the Microenvironmental Landscape in Brain Tumors reveals Disease-specific alterations of Immune cells Cell 2020 181 7 1643 60e17 10.1016/j.cell.2020.05.007 32470396 PMC8558904 · DOI
  5. [5]Bowman RL Klemm F Akkari L Pyonteck SM Sevenich L Quail DF Dhara S Simpson K Gardner EE Iacobuzio-Donahue CA Brennan CW Tabar V Gutin PH Joyce JA Macrophage Ontogeny underlies differences in Tumor-Specific Education in Brain malignancies Cell Rep 2016 17 9 2445 59 10.1016/j.celrep.2016.10.052 27840052 PMC5450644 · DOI
  6. [6]Schulz M Michels B Niesel K Stein S Farin H Rödel F Sevenich L Cellular and Molecular Changes of Brain metastases-Associated myeloid cells during Disease Progression and Therapeutic Response iScience 2020 23 6 101178 10.1016/j.isci.2020.101178 32480132 PMC7262568 · DOI
  7. [7]Ginhoux F Greter M Leboeuf M Nandi S See P Gokhan S Mehler MF Conway SJ Ng LG Stanley ER Samokhvalov IM Merad M Fate mapping analysis reveals that adult microglia derive from primitive macrophages Science 2010 330 6005 841 5 10.1126/science.1194637 20966214 PMC3719181 · DOI · Paper page
  8. [8]Bennett ML Bennett FC Liddelow SA Ajami B Zamanian JL Fernhoff NB Mulinyawe SB Bohlen CJ Adil A Tucker A Weissman IL Chang EF Li G Grant GA Hayden Gephart MG Barres BA New tools for studying microglia in the mouse and human CNS Proc Natl Acad Sci U S A 2016 113 12 E1738 46 10.1073/pnas.1525528113 26884166 PMC4812770 · DOI · Paper page
  9. [9]Satoh J Kino Y Asahina N Takitani M Miyoshi J Ishida T Saito Y TMEM119 marks a subset of microglia in the human brain Neuropathology 2016 36 1 39 49 10.1111/neup.12235 26250788 · DOI · Paper page
  10. [10]Bohnert S Seiffert A Trella S Bohnert M Distel L Ondruschka B Monoranu CM TMEM119 as a specific marker of microglia reaction in traumatic brain injury in postmortem examination Int J Legal Med 2020 134 6 2167 76 10.1007/s00414-020-02384-z 32719959 PMC7578160 · DOI
  11. [11]Mercurio D Fumagalli S Schafer MK Pedragosa J Ngassam LDC Wilhelmi V Winterberg S Planas AM Weihe E De Simoni MG Protein expression of the microglial marker Tmem119 decreases in Association with morphological changes and location in a mouse model of traumatic brain Injury Front Cell Neurosci 2022 16 820127 10.3389/fncel.2022.820127 35221925 PMC8866855 · DOI
  12. [12]Young KF Gardner R Sariana V Whitman SA Bartlett MJ Falk T Morrison HW Can quantifying morphology and TMEM119 expression distinguish between microglia and infiltrating macrophages after ischemic stroke and reperfusion in male and female mice? J Neuroinflammation 2021 18 1 58 10.1186/s12974-021-02105-2 33618737 PMC7901206 · DOI
  13. [13]van Wageningen TA Vlaar E Kooij G Jongenelen CAM Geurts JJG van Dam AM Regulation of microglial TMEM119 and P2RY12 immunoreactivity in multiple sclerosis white and grey matter lesions is dependent on their inflammatory environment Acta Neuropathol Commun 2019 7 1 206 10.1186/s40478-019-0850-z 31829283 PMC6907356 · DOI · Paper page
  14. [14]Kenkhuis B Somarakis A Kleindouwel LRT van Roon-Mom WMC Höllt T van der Weerd L Co-expression patterns of microglia markers Iba1, TMEM119 and P2RY12 in Alzheimer’s disease Neurobiol Dis 2022 167 105684 10.1016/j.nbd.2022.105684 35247551 · DOI · Paper page
  15. [15]Kaiser T, Feng G. Tmem119-EGFP and Tmem119-CreERT2 transgenic mice for labeling and manipulating microglia. eNeuro. 2019;6(4). Epub 20190826. 10.1523/ENEURO.0448-18.2019. PubMed PMID: 31371457; PMCID: PMC6712208. PMC6712208 31371457 · DOI · Paper page
  16. [16]Tan YL Yuan Y Tian L Microglial regional heterogeneity and its role in the brain Mol Psychiatry 2020 25 2 351 67 10.1038/s41380-019-0609-8 31772305 PMC6974435 · DOI · Paper page
  17. [17]Barko K Shelton M Xue X Afriyie-Agyemang Y Puig S Freyberg Z Tseng GC Logan RW Seney ML Brain region- and sex-specific transcriptional profiles of microglia Front Psychiatry 2022 13 945548 10.3389/fpsyt.2022.945548 36090351 PMC9448907 · DOI
  18. [18]Rivest S Molecular insights on the cerebral innate immune system Brain Behav Immun 2003 17 1 13 9 10.1016/S0889-1591(02)00055-7 12615045 · DOI
  19. [19]Henn A Lund S Hedtjärn M Schrattenholz A Pörzgen P Leist M The suitability of BV2 cells as alternative model system for primary microglia cultures or for animal experiments examining brain inflammation Altex 2009 26 2 83 94 10.14573/altex.2009.2.83 19565166 · DOI · Paper page
  20. [20]Dai XJ Li N Yu L Chen ZY Hua R Qin X Zhang YM Activation of BV2 microglia by lipopolysaccharide triggers an inflammatory reaction in PC12 cell apoptosis through a toll-like receptor 4-dependent pathway Cell Stress Chaperones 2015 20 2 321 31 10.1007/s12192-014-0552-1 25387796 PMC4326377 · DOI
  21. [21]Nam HY Nam JH Yoon G Lee JY Nam Y Kang HJ Cho HJ Kim J Hoe HS Ibrutinib suppresses LPS-induced neuroinflammatory responses in BV2 microglial cells and wild-type mice J Neuroinflammation 2018 15 1 271 10.1186/s12974-018-1308-0 30231870 PMC6145206 · DOI
  22. [22]Ma W Oliveira-Nunes MC Xu K Kossenkov A Reiner BC Crist RC Hayden J Chen Q Type I interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitment Nat Commun 2023 14 1 2632 10.1038/s41467-023-38252-8 37149684 PMC10163863 · DOI
  23. [23]Ruan C Elyaman W A New understanding of TMEM119 as a marker of Microglia Front Cell Neurosci 2022 16 902372 10.3389/fncel.2022.902372 35769325 PMC9234454 · DOI · Paper page
  24. [24]Vankriekelsvenne E Chrzanowski U Manzhula K Greiner T Wree A Hawlitschka A Llovera G Zhan J Joost S Schmitz C Ponsaerts P Amor S Nutma E Kipp M Kaddatz H Transmembrane protein 119 is neither a specific nor a reliable marker for microglia Glia 2022 70 6 1170 90 10.1002/glia.24164 35246882 · DOI
  25. [25]Grabert K Michoel T Karavolos MH Clohisey S Baillie JK Stevens MP Freeman TC Summers KM McColl BW Microglial brain region-dependent diversity and selective regional sensitivities to aging Nat Neurosci 2016 19 3 504 16 10.1038/nn.4222 26780511 PMC4768346 · DOI · Paper page
  26. [26]Stowell RD Wong EL Batchelor HN Mendes MS Lamantia CE Whitelaw BS Majewska AK Cerebellar microglia are dynamically unique and survey Purkinje neurons in vivo Dev Neurobiol 2018 78 6 627 44 10.1002/dneu.22572 29285893 PMC6544048 · DOI · Paper page
  27. [28]Keren-Shaul H Spinrad A Weiner A Matcovitch-Natan O Dvir-Szternfeld R Ulland TK David E Baruch K Lara-Astaiso D Toth B Itzkovitz S Colonna M Schwartz M Amit I A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease Cell 2017 169 7 1276 90e17 10.1016/j.cell.2017.05.018 28602351 · DOI · Paper page
  28. [29]Jordão MJC, Sankowski R, Brendecke SM, Sagar, Locatelli G, Tai YH, Tay TL, Schramm E, Armbruster S, Hagemeyer N, Groß O, Mai D, Çiçek Ö, Falk T, Kerschensteiner M, Grün D, Prinz M. Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation. Science. 2019;363(6425). 10.1126/science.aat7554. PubMed PMID: 30679343. 30679343 · DOI · Paper page
  29. [30]Liu H Sun Y Zhang Q Jin W Gordon RE Zhang Y Wang J Sun C Wang ZJ Qi X Zhang J Huang B Gui Q Yuan H Chen L Ma X Fang C Liu YQ Yu X Feng S Pro-inflammatory and proliferative microglia drive progression of glioblastoma Cell Rep 2021 36 11 109718 10.1016/j.celrep.2021.109718 34525361 · DOI
  30. [31]Honarpisheh P Lee J Banerjee A Blasco-Conesa MP d’Aigle J Mamun AA Ritzel RM Chauhan A Ganesh BP McCullough LD Potential caveats of putative microglia-specific markers for assessment of age-related cerebrovascular neuroinflammation J Neuroinflammation 2020 17 1 366 10.1186/s12974-020-02019-5 33261619 PMC7709276 · DOI
  31. [33]Grassivaro F Menon R Acquaviva M Ottoboni L Ruffini F Bergamaschi A Muzio L Farina C Martino G Convergence between Microglia and Peripheral macrophages phenotype during development and neuroinflammation J Neurosci 2020 40 4 784 95 10.1523/JNEUROSCI.1523-19.2019 31818979 PMC6975289 · DOI · Paper page
  32. [34]Wu SY Watabe K The roles of microglia/macrophages in tumor progression of brain cancer and metastatic disease Front Biosci (Landmark Ed) 2017 22 10 1805 29 10.2741/4573 28410147 PMC5658785 · DOI
  33. [35]Paolicelli RC Sierra A Stevens B Tremblay ME Aguzzi A Ajami B Amit I Audinat E Bechmann I Bennett M Bennett F Bessis A Biber K Bilbo S Blurton-Jones M Boddeke E Brites D Brône B Brown GC Butovsky O Carson MJ Castellano B Colonna M Cowley SA Cunningham C Davalos D De Jager PL de Strooper B Denes A Eggen BJL Eyo U Galea E Garel S Ginhoux F Glass CK Gokce O Gomez-Nicola D González B Gordon S Graeber MB Greenhalgh AD Gressens P Greter M Gutmann DH Haass C Heneka MT Heppner FL Hong S Hume DA Jung S Kettenmann H Kipnis J Koyama R Lemke G Lynch M Majewska A Malcangio M Malm T Mancuso R Masuda T Matteoli M McColl BW Miron VE Molofsky AV Monje M Mracsko E Nadjar A Neher JJ Neniskyte U Neumann H Noda M Peng B Peri F Perry VH Popovich PG Pridans C Priller J Prinz M Ragozzino D Ransohoff RM Salter MW Schaefer A Schafer DP Schwartz M Simons M Smith CJ Streit WJ Tay TL Tsai LH Verkhratsky A von Bernhardi R Wake H Wittamer V Wolf SA Wu LJ Wyss-Coray T Microglia states and nomenclature: a field at its crossroads Neuron 2022 110 21 3458 83 10.1016/j.neuron.2022.10.020 36327895 PMC9999291 · DOI · Paper page
  34. [36]Caffarel MM Braza MS Microglia and metastases to the central nervous system: victim, ravager, or something else? J Exp Clin Cancer Res 2022 41 1 327 10.1186/s13046-022-02535-7 36411434 PMC9677912 · DOI
  35. [37]Ransohoff RM A polarizing question: do M1 and M2 microglia exist? Nat Neurosci 2016 19 8 987 91 10.1038/nn.4338 27459405 · DOI · Paper page
  36. [38]Wang J He W Zhang J A richer and more diverse future for microglia phenotypes Heliyon 2023 9 4 e14713 10.1016/j.heliyon.2023.e14713 37025898 PMC10070543 · DOI
  37. [39]Volovitz I Shapira N Ezer H Gafni A Lustgarten M Alter T Ben-Horin I Barzilai O Shahar T Kanner A Fried I Veshchev I Grossman R Ram Z A non-aggressive, highly efficient, enzymatic method for dissociation of human brain-tumors and brain-tissues to viable single-cells BMC Neurosci 2016 17 1 30 10.1186/s12868-016-0262-y 27251756 PMC4888249 · DOI
  38. [40]Kaiser O Aliuos P Wissel K Lenarz T Werner D Reuter G Kral A Warnecke A Dissociated neurons and glial cells derived from rat inferior colliculi after digestion with papain PLoS ONE 2013 8 12 e80490 10.1371/journal.pone.0080490 24349001 PMC3861243 · DOI
  39. [41]Calvo B Rubio F Fernández M Tranque P Dissociation of neonatal and adult mice brain for simultaneous analysis of microglia, astrocytes and infiltrating lymphocytes by flow cytometry IBRO Rep 2020 8 36 47 10.1016/j.ibror.2019.12.004 32215337 PMC7090101 · DOI
  40. [42]He Y Yao X Taylor N Bai Y Lovenberg T Bhattacharya A RNA sequencing analysis reveals quiescent microglia isolation methods from postnatal mouse brains and limitations of BV2 cells J Neuroinflammation 2018 15 1 153 10.1186/s12974-018-1195-4 29788964 PMC5964710 · DOI
  41. [43]Horvath RJ Nutile-McMenemy N Alkaitis MS Deleo JA Differential migration, LPS-induced cytokine, chemokine, and NO expression in immortalized BV-2 and HAPI cell lines and primary microglial cultures J Neurochem 2008 107 2 557 69 10.1111/j.1471-4159.2008.05633 18717813 PMC2581646 · DOI

Cited by

Sorted by citations

Authors
Ma, W., Oswald, J., Rios Angulo, A., & Chen, Q.
Affiliations
The Wistar Institute (US)
Corresponding author
  • Ma, Weili
  • Chen, Qing
ORCID
Venue
BMC Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2024-02-02
Volume
25
Issue
1
Pages
6-6
ISSN
1471-2202 (ISSN-L)
DOI
10.1186/s12868-024-00846-3
PMC
PMC10837931
OpenAlex
W4391486364
Cited by
15
References
2
Citations by year
2026: 8 · 2025: 6 · 2024: 1
FWCI
2.34
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institutes of Health (T32CA009171, R01CA241490)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Brain Metastases and Treatment
Keywords
TMEM119, brain metastases, microglia, bone marrow-derived myeloid cells, microglial markers, BV-2 cells, tumor-associated microglia
MeSH terms
Animals, Brain, Brain Neoplasms, Macrophages, Membrane Proteins, Mice, Transgenic, Microglia, Mice, Tumor Microenvironment

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review