Acquisition of a unique mesenchymal precursor-like blastema state underlies successful adult mammalian digit tip regeneration
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ABSTRACT:
PROVIDER: PRJNA560891 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10003800.fastq.gz | Fastqsanger.gz | |||
| SRR10003801.fastq.gz | Fastqsanger.gz | |||
| SRR10003702.fastq.gz | Fastqsanger.gz | |||
| SRR10003802.fastq.gz | Fastqsanger.gz | |||
| SRR10003703.fastq.gz | Fastqsanger.gz |
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Project description:Here, we investigate the origin and nature of blastema cells that regenerate the adult murine digit tip. We show that Pdgfra-expressing mesenchymal cells in uninjured digits establish the regenerative blastema and are essential for regeneration. Single cell profiling shows that the mesenchymal blastema cells are distinct from both uninjured digit and embryonic limb/digit Pdgfra-positive cells. This unique blastema state is environmentally determined; dermal fibroblasts transplanted into the regenerative, but not non-regenerative, digit express blastema markers and contribute to bone regeneration. Moreover, lineage tracing with single cell profiling indicates that endogenous osteoblasts/osteocytes acquire a blastema mesenchymal transcriptional state and contribute to both dermis and bone regeneration. Thus, mammalian digit tip regeneration occurs via a distinct adult mechanism where the regenerative environment promotes acquisition of a unique blastema state that allows cells from tissues like bone to contribute to regeneration of other mesenchymal tissues such as the dermis.
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Project description:Innate regeneration following digit tip amputation is one of the few examples of epimorphic regeneration in mammals. Digit tip regeneration is mediated by the blastema, the same structure invoked during limb regeneration in some lower vertebrates. By genetic lineage analyses in mice, the digit tip blastema has been defined as a population of heterogeneous, lineage restructed progenitor cells. These previous studies, however, do not comprehensively evaluate blastema heterogeneity or address lineage restruction of closely related cell types. Here we report single cell RNA sequencing of over 38,000 cells from mouse digit tip blastemas and unamputated control digit tips and generate an atlas of the cell types participating in digit tip regeneration.
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