Correction: Pleiotropic Impacts of Macrophage and Microglial Deficiency on Development in Rats with Targeted Mutation of the <i>Csf1r</i> Locus

Pridans, Clare; Raper, Anna; Davis, Gemma M.; Alves, Joana; Sauter, Kristin A.; Lefèvre, Lucas; Regan, Tim; Meek, Stephen; Sutherland, Linda; Thomson, Axel A.; Clohisey, Sara; Bush, Stephen J.; Rojo, Rocío; Lisowski, Zofia M.; Wallace, Robert; Grabert, Kathleen; Upton, Kyle R.; Tsai, Yi Ting; Brown, Deborah; Smith, Lee B.; Summers, Kim M.; Mabbott, Neil A.; Piccardo, Pedro; Cheeseman, Michael; Burdon, Tom; Hume, David

doi:10.4049/jimmunol.1900420

Cited by 29 publications

(106 citation statements)

References 0 publications

Supporting

Mentioning

101

Contrasting

Order By: Relevance

“…Recently, patients carrying homozygous mutations in CSF1R and presenting with both leukodystrophy and osteopetrosis, phenotypes attributed to an absence of TRMs in the brain and bone, have been described (Oosterhof et al, 2019b). In mice and rats, the absence of CSF1R results in a complete lack of microglia, Langerhans cells (LCs), and osteoclasts, while other subsets of TRMs are affected to varying degrees (Cecchini et al, 1994; Dai et al, 2002; Erblich et al, 2011; Ginhoux et al, 2010; Oosterhof et al, 2018b; Pridans et al, 2018). It is unknown whether CSF1R is required for the development of early, embryonic TRM precursors and it remains elusive as to why only specific TRM populations are lacking in the absence of Csf1r .…”

Section: Introductionmentioning

confidence: 99%

Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes

Kuil

Oosterhof

Ferrero

et al. 2020

Preprint

View full text Add to dashboard Cite

20Macrophages derive from multiple sources of hematopoietic progenitors. Most macrophages 21 require colony-stimulating factor 1 receptor (CSF1R), but some macrophages persist in the 22 absence of CSF1R. Here, we analyzed mpeg1:GFP-expressing macrophages in csf1r-23 deficient zebrafish and report that embryonic macrophages emerge followed by their 24 developmental arrest. In larvae, mpeg1+ cell numbers then increased showing two distinct 25 types in the skin: branched, putative Langerhans cells, and amoeboid cells. In contrast, 26 although numbers also increased in csf1r-mutants, exclusively amoeboid mpeg1+ cells were 27 present, which we showed by genetic lineage tracing to have a non-hematopoietic origin. 28They expressed macrophage-associated genes, but also showed decreased phagocytic 29 gene expression and increased epithelial-associated gene expression, characteristic of 30 metaphocytes, recently discovered ectoderm-derived cells. We further demonstrated that 31 juvenile csf1r-deficient zebrafish exhibit systemic macrophage depletion. Thus, Csf1r 32 deficiency disrupts embryonic to adult macrophage development. Csf1r-deficient zebrafish 33 are viable and permit analyzing the consequences of macrophage loss throughout life. 34 35 36 106 fate mapping and gene expression profiling, we identified csf1r DM mpeg1+ cells as 107 metaphocytes, a population of ectoderm-derived macrophage-like cells recently reported in 108 zebrafish (Alemany et al., 2018a; Lin et al., 2019). Extending our analyses, we further 109 demonstrated that adult csf1r DM fish exhibit a global defect in macrophage generation. In 110 5 conclusion, our study highlights distinct requirements for Csf1r during macrophage 111 generation and metaphocyte ontogeny, resolving part of the presumed macrophage 112 heterogeneity and their sensitivity to loss of Csf1r. 113 Results 114Zebrafish embryonic macrophages are formed independently of csf1r but display 115 migration and proliferation defects 207 both csf1r DM primitive macrophages and early microglia. 208Next, we assessed the presence of macrophages in developing csf1r DM animals by in 209 vivo fluorescence imaging of one lateral side of entire, individual larvae on 4 consecutive 210 days, starting at 5 dpf. We visualized ~450 macrophages in control animals, whereas csf1r DM 211 animals contained > 4-fold fewer (~100) ( Figure 3D). Over the next 4 days, macrophage 212 numbers in both groups remained stable ( Figure 3D). This suggests that, at this stage, there 213 is neither proliferative expansion of embryonic macrophages nor supply of macrophages 214 from an alternative source, causing macrophage numbers in csf1r DM larvae to remain much 215 lower than those in controls up to 9 dpf. Together these data indicate that, onwards from the 216 initiation of embryonic tissue colonization, proliferative expansion of macrophages remains 217 halted in csf1r DM animals.218 219 csf1r DM skin lacks highly branched putative Langerhans cells 220 8Given that macrophages are produced by consecutive waves of primiti...

show abstract

Section: Introductionmentioning

confidence: 99%

Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes

Kuil

Oosterhof

Ferrero

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Genes in Cluster 4 were strongly expressed in samples from brain and include microglia-enriched markers that are depleted in brains of Csf1r-deficient mice and rats such as Cx3cr1, Tmem119, P2ry12 and the key transcription factor genes Sall1, Sall2 and Sall3 [16,61]. Cluster 9 contains the S phase transcription factor gene Foxm1 and numerous cell cycle-associated transcripts [62] and the GO term enrichment supports the cell cycle association.…”

Section: Major Macrophage-enriched Co-regulated Clustersmentioning

confidence: 70%

“…Transcripts in Cluster 4 were enriched in the resident kidney macrophages compared to both splenic macrophages and other kidney myeloid populations. Interestingly, the resident kidney macrophage cluster includes many genes that are also highly-expressed in microglia and depleted in the brain in Csf1r mutant mice and rats, including Cx3cr1, C1qa/b/c, Csf3r, Ctss, Fcrls, Hexb, Laptm5, Tgfbr1, Tmem119 and Trem2 [16,61]. These were also detected in the isolated kidney macrophages in Table S1.…”

Section: Validation Of Co-expression Clustering With An Independent Kmentioning

confidence: 90%

“…Both populations of interstitial lung macrophages (and all the samples from other tissues in this BioProject) expressed very high levels of all of the IEG transcripts in Cluster 41. Whereas macrophageexpressed transcripts such as Adgre1 are readily detected in total tissue mRNA, and are CSF1Rdependent, inflammatory cytokines and IEG are not [16,61]. Accordingly, in each of these studies, the expression of IEG and inducible cytokines is most likely an artefact of tissue disaggregation.…”

Section: Resident Macrophage Activation During Isolationmentioning

confidence: 94%

“…In mice there are multiple Cd209 paralogs. Cd209b was highly-expressed in marginal zone macrophage populations in spleen and is Csf1rdependent [61]. These cells have not been successfully isolated by tissue disaggregation.…”

Section: Dendritic Cell Co-expression Clustersmentioning

confidence: 99%

See 2 more Smart Citations

Transcriptional network analysis of transcriptomic diversity in resident tissue macrophages and dendritic cells in the mouse mononuclear phagocyte system

Hume

2020

Preprint

Self Cite

View full text Add to dashboard Cite

The mononuclear phagocyte system (MPS) is a family of cells including progenitors, circulating blood monocytes, resident tissue macrophages and dendritic cells (DC) present in every tissue in the body. To test the relationships between markers and transcriptomic diversity in the MPS, we collected from NCBI-GEO >500 quality RNA-seq datasets generated from mouse MPS cells isolated from multiple tissues. The primary data were randomly down-sized to a depth of 10 million reads and requantified. The resulting dataset was clustered using the network analysis tool Graphia. A sample-to-sample matrix revealed that MPS populations could be separated based upon tissue of origin. Cells identified as classical DC subsets, cDC1 and cDC2, and lacking Fcgr1 (CD64), were centrally-located within the MPS cluster and no more distinct than other MPS cell types. A gene-to-gene correlation matrix identified large generic co-expression clusters associated with MPS maturation and innate immune function. Smaller co-expression clusters including the transcription factors that drive them showed higher expression within defined isolated cells, including macrophages and DC from specific tissues. They include a cluster containing Lyve1 that implies a function in endothelial cell homeostasis, a cluster of transcripts enriched in intestinal macrophages and a generic cDC cluster associated with Ccr7. However, transcripts encoding many other putative MPS subset markers including Adgre1, Itgax, Itgam, Clec9a, Cd163, Mertk, Retnla and H2-A/E (class II MHC) clustered idiosyncratically and were not correlated with underlying functions. The data provide no support for the concept of markers of M2 polarization or the specific adaptation of DC to present antigen to T cells. Co-expression of immediate early genes (e.g. Egr1, Fos, Dusp1) and inflammatory cytokines and chemokines (Tnf, Il1b, Ccl3/4) indicated that all tissue disaggregation protocols activate MPS cells. Tissue-specific expression clusters indicated that all cell isolation procedures also co-purify other unrelated cell types that may interact with MPS cells in vivo. Comparative analysis of public RNA-seq and single cell RNA-seq data from the same lung cell populations showed that the extensive heterogeneity implied by the global cluster analysis may be even greater at a single cell level with few markers strongly correlated with each other. This analysis highlights the power of large datasets to identify the diversity of MPS cellular phenotypes, and the limited predictive value of surface markers to define lineages, functions or subpopulations.

show abstract

Origins and diversity of macrophages in health and disease

et al. 2020

View full text Add to dashboard Cite

Macrophages are the first immune cells in the developing embryo and have a central role in organ development, homeostasis, immunity and repair. Over the last century, our understanding of these cells has evolved from being thought of as simple phagocytic cells to master regulators involved in governing a myriad of cellular processes. A better appreciation of macrophage biology has been matched with a clearer understanding of their diverse origins and the flexibility of their metabolic and transcriptional machinery. The understanding of the classical mononuclear phagocyte system in its original form has now been expanded to include the embryonic origin of tissue‐resident macrophages. A better knowledge of the intrinsic similarities and differences between macrophages of embryonic or monocyte origin has highlighted the importance of ontogeny in macrophage dysfunction in disease. In this review, we provide an update on origin and classification of tissue macrophages, the mechanisms of macrophage specialisation and their role in health and disease. The importance of the macrophage niche in providing trophic factors and a specialised environment for macrophage differentiation and specialisation is also discussed.

show abstract

Correction: Pleiotropic Impacts of Macrophage and Microglial Deficiency on Development in Rats with Targeted Mutation of the Csf1r Locus

Abstract: 2018. Pleiotropic impacts of macrophage and microglial deficiency on development in rats with targeted mutation of the Csf1r locus.

Cited by 29 publications

References 0 publications

Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes

Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes

Transcriptional network analysis of transcriptomic diversity in resident tissue macrophages and dendritic cells in the mouse mononuclear phagocyte system

Origins and diversity of macrophages in health and disease

Contact Info

Product

Resources

About