Microglia’s heretical self-renewal

Rossi, Fábio; Lewis, Coral Ann B.

doi:10.1038/s41593-018-0123-3

Cited by 9 publications

(6 citation statements)

References 14 publications

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“…In the uninjured brain, microglia have limited self-renewal capacities 21 . The presence of three clusters of microglia in GBM may represent a functional categorization.…”

Section: Resultsmentioning

confidence: 99%

Single-cell RNA sequencing reveals evolution of immune landscape during glioblastoma progression

et al. 2022

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Glioblastoma (GBM) is an incurable primary malignant brain cancer hallmarked with a substantial protumorigenic immune component. Knowledge of the GBM immune microenvironment during tumor evolution and standard of care treatments is limited. Using single-cell transcriptomics and flow cytometry, we unveiled large-scale comprehensive longitudinal changes in immune cell composition throughout tumor progression in an epidermal growth factor receptor-driven genetic mouse GBM model. We identified subsets of proinflammatory microglia in developing GBMs and anti-inflammatory macrophages and protumorigenic myeloid-derived suppressors cells in end-stage tumors, an evolution that parallels breakdown of the blood–brain barrier and extensive growth of epidermal growth factor receptor+ GBM cells. A similar relationship was found between microglia and macrophages in patient biopsies of low-grade glioma and GBM. Temozolomide decreased the accumulation of myeloid-derived suppressor cells, whereas concomitant temozolomide irradiation increased intratumoral GranzymeB+ CD8+T cells but also increased CD4+ regulatory T cells. These results provide a comprehensive and unbiased immune cellular landscape and its evolutionary changes during GBM progression.

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“…In the uninjured brain, microglia have limited self-renewal capacities 21 . The presence of three clusters of microglia in GBM may represent a functional categorization.…”

Section: Resultsmentioning

confidence: 99%

Single-cell RNA sequencing reveals evolution of immune landscape during glioblastoma progression

et al. 2022

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“…Being the tissue macrophages in CNS, adult microglia are critical in keeping normal physiological function and in responding to pathological damages in CNS 3 . One character of adult microglia is that they can proliferate at homeostatic physiological condition and upon pathological stimulations 4 – 9 . Compared with embryonic microglia, which are highly proliferative 1 , adult microglia have a low rate of baseline proliferation to maintain their homeostatic population 5 – 7 .…”

Section: Introductionmentioning

confidence: 99%

Distinct phases of adult microglia proliferation: a Myc-mediated early phase and a Tnfaip3-mediated late phase

Tan

Leff

et al. 2022

Cell Discov

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Microgliosis is a hallmark of many neurological diseases, including Alzheimer’s disease, stroke, seizure, traumatic brain and spinal cord injuries, and peripheral and optic nerve injuries. Recent studies have shown that the newly self-renewed microglia have specific neurological functions. However, the mechanism of adult microglia proliferation remains largely unclear. Here, with single-cell RNA sequencing, flow cytometry, and immunohistochemistry, we demonstrate that the sciatic nerve injury induced two distinct phases of microglia proliferation in mouse spinal cord, each with different gene expression profiles. We demonstrate that the transcription factor Myc was transiently upregulated in spinal cord microglia after nerve injury to mediate an early phase microglia proliferation. On the other hand, we reveal that the tumor-necrosis factor alpha-induced protein 3 (Tnfaip3) was downregulated to mediate the Myc-independent late-phase microglia proliferation. We show that cyclin dependent kinase 1, a kinase with important function in the M phase of the cell cycle, was involved only in the early phase. We reveal that although the early phase was neither necessary nor sufficient for the late phase proliferation, the late-phase suppressed the early phase microglia proliferation in the spinal cord. Finally, we demonstrate that the termination of spinal cord microglia proliferation required both Myc and Tnfaip3 to resume their baseline expression. Thus, we have delineated an interactive signaling network in the proliferation of differentiated microglia.

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“…The advancement of technology gives us opportunities to learn more in this area that have never existed before. Microglia is a differentiated cell that can self-renew ( 25 ), while BMDMs replenish through peripheral monocytosis ( 24 ). Under physiological settings, microglia appear in a ramified resting status, but when activated, they transform into hypertrophic and finally ameboid active forms ( 14 ).…”

Section: Time and Clinical Practicementioning

confidence: 99%

Microenvironment and the progress of immunotherapy in clinical practice of NSCLC brain metastasis

Xie

2023

Front. Oncol.

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One of the most frequent distant metastases of lung cancer occurs in the brain. The average natural survival duration for patients with lung cancer who have brain metastases is about 1 to 2 months. Knowledge about brain metastases is currently restricted since they are more difficult to acquire than other metastases. This review begins with an analysis of the immune microenvironment of brain metastases; focuses primarily on the functions of microglia, astrocytes, neurons, and tumor-infiltrating lymphocytes in the microenvironment of brain metastases; and offers an atlas of the immune microenvironment of brain metastases involving significant cells. In an effort to give researchers new research ideas, the study also briefly covers how immunotherapy for non-small cell lung cancer with brain metastases is currently faring.

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Microglia’s heretical self-renewal

Cited by 9 publications

References 14 publications

Single-cell RNA sequencing reveals evolution of immune landscape during glioblastoma progression

Single-cell RNA sequencing reveals evolution of immune landscape during glioblastoma progression

Distinct phases of adult microglia proliferation: a Myc-mediated early phase and a Tnfaip3-mediated late phase

Microenvironment and the progress of immunotherapy in clinical practice of NSCLC brain metastasis

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