Organism-wide mapping of MHC class I and II expression in mouse lemur cells and tissues

Abstract

The major histocompatibility complex (MHC) class I and II glycoproteins have been associated with numerous disease phenotypes, mechanisms and outcomes. These associations can be due to allotypic polymorphism or to altered levels of allotype expression. Although well studied in a range of cell types and microenvironments, no study has encompassed all cell-types present in an individual mouse lemur. In this study the droplet-based single cell RNA sequence data from the mouse lemur cell atlas, Tabula Microcebus, were used to examine the patterns of MHC class I and II expression. The cell atlas comprises data obtained from 27 organs from four mouse lemurs, enabling comparison of expression pattern between both cell types and the individual lemurs. Patterns of gene expression showed a good concordance among the four mouse lemurs. Three primary patterns of expression were identified and associated with different cell-types. Mapping MHC expression onto existing cell trajectories of cell development and spatial gradients revealed fine scale differences in expression level and pattern in single tissues. The bioinformatic pipeline developed here is applicable to other cell atlas projects.

Mouse lemur transcriptomic atlas informs primate genes, mutations, physiology, and disease

“…S4b). DQA, DQB, DRA, and DRB are expressed at higher levels and in more cells than the other class II genes ( DMA, DMB, DPA, DPB ) 50 (Fig. 4d).…”

“… c. Number of putative alleles for each MHC gene in the four lemurs (L1-L4), and number of genes annotated in the BAC and by NCBI (note some class I sequences differ only by a few base pairs among haplotypes (see accompanying MHC manuscript 50 ), therefore the number of alleles in the panel represents our best estimate but may be inexact due to sequencing errors or other technical artifacts). Genes that exhibit copy number variation (C) or have at least one allele that is a pseudogene (P) are indicated below each panel.…”

“…4c), further highlighting the polymorphic nature of the gene complex. The current genome assembly (Mmur 3.0 22 ) contains gaps separating the complex into three sequence islands, rearrangement of which better matches the available BAC sequence 51 , as detailed in Guethlein et al 50 ; long range sequencing is needed to reveal the full number and order of genes for each individual (Fig. 4b).…”

“…4a, c). The other class II genes all appear to be single, non-duplicated genes, including two ( DQA, DQB) that are currently annotated as duplicated (assembly: Mmur 3.0 22 , annotation NCBI Refseq Annotation Release 101) and one ( DRB ) as triplicated, the latter from failed assembly of two genomic fragments of the second DRB allele 50 (Fig. S4b).…”

“…DRB1-10 is predicted to encode a full length DRB1 polypeptide, whereas DRB1-1 and DRB1-4 are incomplete and contain non-MHC sequences (gray shading). Note that the MHC sequences in DRB1-1 and DRB1-4 encode a functional DRB polypeptide, suggesting that these sequences were misassembled and belong together to form a second complete DRB1 allele 50 . Thin vertical lines, positions that differ between the three sequences.…”