Journal: BMC Genomics

Article Title: Discovery of NRG1-VII: the myeloid-derived class of NRG1

doi: 10.1186/s12864-024-10723-2

Figure Lengend Snippet: Identification of a myeloid specific TSS in the human NRG1 locus. A Screenshot of the ZENBU genome browser showing the Gencode v22 transcript track, (accessed 26/1/23 ) corresponding to the FANTOM5 phase 1 and 2 TSS peaks overlapping the starting exon of NRG1 class VII. Red vertical line encased in blue dashed box indicates the position for the TSS of interest. Tag selection (grey bar, FANTOM5 CAGE track) indicates region for tag quantification in the FANTOM5 experiment table. The table is truncated to show the top 6 samples are primary myeloid cells, representative of the top 57/115 samples with > 1TPM) Experimental samples are ordered by highest number of CAGE tags counted in this area on sense strand (green bars, showing counts as TPM). B Schematic of the human NRG1 locus highlighting alternate transcriptional starting exons that correspond to seven isoform classes. The schematic shows 5’ exon composition until the first shared exon (containing the EGF domain). Exons are numbered by ENSEMBL accessions. C Alignment of mRNA and protein sequences of NRG1 class I and class VII to show an in-frame translation initiation of NRG1 class VII. Initiating methionine (M) or start codon (ATG) in red text. The blue arrow shows the target sequence of the forward primer for NRG1-VII mRNA’s unique 5’ UTR. The NRG1-VII transcript start is conserved in other mammalian genomes (Sup. Fig. 1)

Article Snippet: Our investigation of NRG1 expression in the public single cell atlases, including the Human Protein Atlas mRNA dataset, suggested that macrophages are a major source of NRG1 in most tissues.

Techniques: Selection, Sequencing

Journal: BMC Genomics

Article Title: Discovery of NRG1-VII: the myeloid-derived class of NRG1

doi: 10.1186/s12864-024-10723-2

Figure Lengend Snippet: NRG1 expression profile in myeloid cells. A Quantification of NRG1 mRNA expression in different human tissues according to The Human Protein Atlas . A plethora of representative tissues that express NRG1 are shown here. The y axis represents nTPM (Number of transcripts per million). Neurons shown in yellow, myeloid cells in red, other cell types in grey. B qRT-PCR data measuring presence of the different NRG1 classes in different cell types. Classes IV-VI were not detected in any of the samples. Expression ratios include Pfaffl primer efficiency . Mono = Monocyte, Mφ: macrophage, iPSC: Induced pluripotent stem cell. Monocytes, monocyte derived macrophages and adipose tissue macrophages were isolated from patients. 2D macrophages and cortical neurons are derived using Kolf2.1 iPSCs. iPSCs and 3D macrophages are PB001.1 cells. C Time series showing qRT-PCR expression of typical myeloid markers in progenitor maturation (PB001.1) and relationship with myeloid specific NRG1-VII transcripts. D Immunostaining of GBM showing presence of CD68 + cells that express NRG1 peptides in vivo. The left panel shows sample section stained with DAPI. The boxes indicate the regions shown in the right panel in D and the cell in E, respectively. Scale bar on left panel is 1 mm, scale bar on right panel represents 20 μm. E Example of cell in which all markers (CD68, NRG1-EGF and NRG1-ICD) are expressed. Scale bars = 20 μm

Article Snippet: Our investigation of NRG1 expression in the public single cell atlases, including the Human Protein Atlas mRNA dataset, suggested that macrophages are a major source of NRG1 in most tissues.

Techniques: Expressing, Quantitative RT-PCR, Derivative Assay, Isolation, Immunostaining, In Vivo, Staining