Generation and network analysis of an RNA-seq transcriptional atlas for the rat

Abstract

The laboratory rat is an important model for biomedical research. To generate a comprehensive rat transcriptomic atlas, we curated and downloaded 7700 rat RNA-seq datasets from public repositories, downsampled them to a common depth and quantified expression. Data from 585 rat tissues and cells, averaged from each BioProject, can be visualized and queried at http://biogps.org/ratatlas. Gene co-expression network (GCN) analysis revealed clusters of transcripts that were tissue or cell type restricted and contained transcription factors implicated in lineage determination. Other clusters were enriched for transcripts associated with biological processes. Many of these clusters overlap with previous data from analysis of other species, while some (e.g. expressed specifically in immune cells, retina/pineal gland, pituitary and germ cells) are unique to these data. GCN analysis on large subsets of the data related specifically to liver, nervous system, kidney, musculoskeletal system and cardiovascular system enabled deconvolution of cell type-specific signatures. The approach is extensible and the dataset can be used as a point of reference from which to analyse the transcriptomes of cell types and tissues that have not yet been sampled. Sets of strictly co-expressed transcripts provide a resource for critical interpretation of single-cell RNA-seq data.

CSF1R as a Therapeutic Target in Bone Diseases: Obvious but Not so Simple

“…In adult mice, Csf1r mRNA and protein are absent from pluripotent hematopoietic stem cells in the bone marrow [31, 32•, 33] and induced during differentiation/lineage commitment in myeloid progenitors. Csf1r mRNA is expressed by blood monocytes, granulocytes, tissue macrophages, dendritic cells, and OCL [33][34][35]. In granulocytes, Csf1r mRNA is coexpressed with several other macrophage-specific transcripts that are not translated into protein [34].…”

Intraperitoneal transfer of wild-type bone marrow cells in theCsf1rknockout rat repopulates resident tissue macrophages without contributing to monocytopoiesis

“…Classical dendritic cells in the rat have not been well-defined [2] and there are currently no definitive markers. However, FLT3 ligand ( Flt3lg ) is highly expressed by rat T cells ([37]; biogps.org/ratatlas) so it is likely that these CSF1R-independent populations are maintained by FLT3 signalling.…”

Intraperitoneal transfer of wild‐type bone marrow repopulates tissue macrophages in the Csf1r knockout rat without contributing to monocytopoiesis

“…Classical DCs in the rat have not been well defined [2] and there are currently no definitive markers. However, FLT3 ligand ( Flt3lg ) is highly expressed by rat T cells ([37]; biogps.org/ratatlas) so it is likely that these CSF1R‐independent populations are maintained by FLT3 signaling.…”