MME+ fibro-adipogenic progenitors are the dominant adipogenic population during fatty infiltration in human skeletal muscle
About the project:
Fatty infiltration, the ectopic deposition of adipose tissue within skeletal muscle, is mediated via the adipogenic differentiation of fibro-adipogenic progenitors (FAPs). We used single-nuclei and single-cell RNA sequencing to characterize FAP heterogeneity in patients with fatty infiltration. We identified an MME+ FAP subpopulation which, based on ex vivo characterization as well as transplantation experiments, exhibits high adipogenic potential. MME+ FAPs are characterized by low activity of WNT, known to control adipogenic commitment, and are refractory to the inhibitory role of WNT activators. Using preclinical models for muscle damage versus fatty infiltration, we show that many MME+ FAPs undergo apoptosis during muscle regeneration and differentiate into adipocytes under pathological conditions, leading to their depletion. Finally, we utilized the varying fat infiltration levels in human hip muscles to show the depletion of MME+ FAPs in fatty infiltrated human muscle. Altogether, we have identified the dominant adipogenic FAP subpopulation in skeletal muscle.
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Information available on the Explorer:
Human scRNAseq: Visualization of gene expression and cell type information of human skeletal muscle (single-cell RNAseq) in TSNE and Violin plots. Standard clustering and unbiased mappings to datasets from Rubenstein et al. and De Micheli et al. are available to explore.
Human 3D scRNAseq: 3D visualization of gene expression and cell type information of human skeletal muscle (single-cell RNAseq) for a better interpretation of the structure of the data.
Human snRNAseq: Visualization of gene expression and cell type information of FAPs and adipocytes from human skeletal muscle (single-nuclei RNAseq) in TSNE and Violin plots.
Mouse scRNAseq: Visualization of gene expression and cell type information of FAPs from mouse skeletal muscle (single-cell RNAseq) in TSNE and Violin plots.
Mouse bulk RNAseq: Visualization of normalized gene counts and custom heatmaps of FACS sorted MME+ and MME- FAPs from mouse skeletal muscle (bulk RNAseq). Full RNAseq data of MME+ vs MME- comparison is available to download.
Contact information:
For questions or suggestions about the project, please contact Prof. Dr. Katrien De Bock at katrien-debock@ethz.ch
Website developed and maintained by Guillermo Turiel. For website questions, suggestions or issues, please contact Guillermo Turiel at guillermo.turiel@hest.ethz.ch
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