Microfibril-associated glycoprotein 4 (Mfap4) regulates haematopoiesis in zebrafish

Abstract

Microfibril-associated glycoprotein 4 (MFAP4) is an extracellular matrix protein belonging to the fibrinogen-related protein superfamily. MFAP4 is produced by vascular smooth muscle cells and is highly enriched in the blood vessels of the heart and lung, where it is thought to contribute to the structure and function of elastic fibers. Genetic studies in humans have implicated MFAP4 in the pathogenesis of Smith-Magenis syndrome, in which patients present with multiple congenital abnormalities and mental retardation, as well as in the severe cardiac malformation left-sided congenital heart disease. Comprehensive genetic analysis of the role of MFAP4 orthologues in model organisms during development and tissue homeostasis is however lacking. Here, we demonstrate that zebrafish mfap4 transcripts are detected embryonically, resolving to the macrophage lineage by 24 h post fertilization. mfap4 null mutant zebrafish are unexpectedly viable and fertile, without ostensible phenotypes. However, tail fin amputation assays reveal that mfap4 mutants have reduced numbers of macrophages, with a concomitant increase in neutrophilic granulocytes, although recruitment of both cell types to the site of injury was unaffected. Molecular analyses suggest that loss of Mfap4 alters the balance between myeloid and lymphoid lineages during both primitive and definitive haematopoiesis, which could significantly impact the downstream function of the immune system.

Characterization of the innate immune response to Streptococcus pneumoniae infection in zebrafish

“…Also, a macrophage-specific gene aconitate decarboxylase 1, acod1 (also known as immunoresponsive 1 homolog, irg1), which is known to be highly expressed under bacterial infections and to be important for the production of reactive oxygen species by macrophages [70,71], was among the most induced genes in pneumococcal infection. Moreover, consistent with the previous studies on Staphylococcus epidermis-responsive genes in zebrafish, two duplicates of the gene microfibril associated protein 4 (mfap4.5 and mfap4.2), a well-known macrophage marker shown to promote macrophage differentiation during hematopoiesis in zebrafish [72,73], were also upregulated upon infection. Of note, while not quite reaching the cutoff levels set for the induced genes, the induction of the genes for common pro-inflammatory cytokines Il1b (4.4-fold induction) and Il6 (9.9-fold induction) was also evident, with mean normalized read counts of 14 and 4.6 in challenged larvae, and 3 and 0.3 in unchallenged larvae, respectively.…”

Single-Cell Transcriptomic Sequencing Analyses of Cell Heterogeneity During Osteogenesis of Human Adipose-Derived Mesenchymal Stem Cells

“…When comparing clusters 0‐2 alone, each cluster was characterized by a small number of DEGs (47, 107, and 112 genes, respectively; Table S5, Figure S3A). The DEGs of cluster 1 included dermatopontin ( DPT ; Figure 4) and microfibril associated protein 4 ( MFAP4 ) gene, both of which were important for stem cell niche 25,26 . Cluster 2 was characterized by fibrillin 1 ( FBN1 ), serpin family E member 2 ( SERPINE2 ), integrin subunit beta like 1 ( ITGBL1 ), PDZ and LIM domain 5 ( PDLIM5 ), and filamin A ( FLNA ).…”

“…The DEGs of cluster 1 included dermatopontin (DPT; Figure 4) and microfibril associated protein 4 (MFAP4) gene, both of which were important for stem cell niche. 25,26 Cluster 2 was characterized by fibrillin 1 (FBN1), serpin F I G U R E 1 Identification of human adipose mesenchymal stem cells (hAMSCs). A, hAMSCs are characterized with five surface markers showing the potential of HSC to differentiate toward adipocytes (B) and osteocytes (C and D).…”

Five immune-related genes as diagnostic markers for endometriosis and their correlation with immune infiltration

“…Therefore, abnormal cell migration and invasion are important for the pathogenesis of EMS. MFAP4, a member of the extracellular matrix, acts as a ligand and participates in the recognition of adhesion and biochemical interactions between cells, as well as in the formation of elastic fibers ( 31 ). Studies have shown that the upregulation of MFAP4 can inhibit the effect of miRNA (Mir)-147b on cell malignant invasiveness ( 32 , 33 ).…”