Distinct Gene Expression Profiles Characterize Cellular Phenotypes of Follicle-Associated Epithelium and M Cells

Abstract

Follicle-associated epithelium (FAE) covering Peyer's patches contains specialized epithelial M cells that take up ingested macromolecules and microorganisms from the lumen of the gut by transcytosis. Using high-density oligonucleotide microarrays, we analyzed the gene expression profiles of FAE and M cells in order to characterize their cellular phenotypes. The microarray data revealed that, among approximately 14,000 genes, 409 were expressed in FAE at twofold or higher levels compared to the intestinal epithelial cells (IECs) of the villi. These included genes involved in membrane traffic, host defense and transcriptional regulation, as well as uncharacterized genes. Real-time PCR and in situ hybridization analyses identified three molecules, ubiquitin D (Ub-D), tumor necrosis factor receptor superfamily 12a (TNFRsf12a), and transmembrane 4 superfamily 4 (Tm4sf4), which were predominantly distributed throughout FAE, but were expressed little, if at all, in IECs. By contrast, transcripts of secretory granule neuroendocrine protein 1 (Sgne-1) were scattered in FAE, and were co-localized with Ulex europaeus agglutinin-1 (UEA-1)-positive cells. This clearly suggests that expression of Sgne-1 in the gut is specific to M cells. Such a unique pattern of gene expression distinguishes FAE and M cells from IECs, and may reflect their cellular phenotype(s) associated with specific functional features.

Comprehensive Gene Expression Profiling of Peyer’s Patch M Cells, Villous M-Like Cells, and Intestinal Epithelial Cells

“…The relative expression levels and gene names of the significant probes are provided in Supplementary Table I. 5 Our gene-profiling database allowed us to confirm previous findings that Group A includes the transcripts of peptidoglycan recognition protein-S, secretory granule neuroendocrine protein 1, and annexin V that are specifically expressed by PP M cells (4 -6).…”

“…Candidates for FAE-specific genes including MLP (also known as MacMARCKS or MRP) have been previously proposed (5,6). Most of these genes together with MLP could be identified as PP M cell-significant genes by the DNA microarray analysis (Supplementary Table I).…”

The macroPARP genes parp‐9 and parp‐14 are developmentally and differentially regulated in mouse tissues

“…2M). The FAE might be immunologically activated by the immune cells from the lymphoid follicles (Hase et al, 2005). This finding could explain why Parp-9 and Parp-14 expression is increased in this epithelium, assuming that both genes could be upregulated by immunological signals, as described at least for the Parp-9 gene that responds to IFN␥ (Juszczynski et al, 2006).…”

“…2N). These specialized epithelial cells possess an immune program, rather than the digestive program typical of the adjacent enterocytes of the villi (Hase et al, 2005). Of interest, Parp-14 transcripts were detected in the FAE (Fig.…”

Roundtrip Ticket for Secretory IgA: Role in Mucosal Homeostasis?

“…The existence of M cells outside the FAE capable to sample Salmonella, Yersinia, and gut bacterial Ags has been reported in intestinal villi in mice devoid of Peyer's patches (19). Labeling with the novel M cell-specific marker secretory granule neuroendocrine protein-1 should help to establish the possibly related phenotype of such cells (20).…”