Biology subjects

Turiel, G.

Publications and source records attributed to Turiel, G..

2 recordsLinked to original sources

bioRxiv2023

Single cell compendium of the muscle microenvironment in peripheral artery disease reveals capillary endothelial heterogeneity and activation of resident macrophages

AO_SCPLOWBSTRACTC_SCPLOWPeripheral artery disease (PAD) results from atherosclerosis and chronic narrowing of lower limb arteries leading to decreased muscle perfusion. Current treatments are suboptimal, partly due to limited understanding of PAD muscle pathology. Here we use scRNAseq and spatial transcriptomics to analyze the composition of the muscle microenvironment in non-ischemic and PAD patients. We identified ATF3/4+ endothelial cells (ECs) that exhibit altered angiogenic and immune regulatory profiles during PAD and confirmed that ATF4 signaling in ECs is required for effective ischemia recovery. Also, capillary ECs display features of endothelial-to-mesenchymal transition. Furthermore, LYVE1hiMHCIIlow macrophages are the dominant macrophage population in human muscle, adopting a more pro-inflammatory profile during PAD. Finally, we analyzed alterations in intercellular communication within the muscle microenvironment during PAD and confirmed that EC-derived factors can influence macrophage polarization. This dataset deeply characterizes the PAD muscle microenvironment and provides a resource for exploration of targeted therapies.

cell biology↗

bioRxiv2022

MME+ fibro-adipogenic progenitors are the dominant adipogenic population during fatty infiltration in human skeletal muscle

Summary/Abstract 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.

cell biology↗