Highlights d Arcellinida testate amoebae are comprised of seven major lineages d Reconstructed hypothetical ancestral states are congruent with Tonian fossils d Combined analysis of phylogenies and fossils suggest divergence as early as 730 mya
Background
Peripheral arterial disease (PAD) affects millions of people and compromises quality of life. Critical limb ischemia (CLI), which is the most advanced stage of PAD, can cause nonhealing ulcers and strong chronic pain, and it shortens the patients’ life expectancy. Cell-based angiogenic therapies are becoming a real therapeutic approach to treat CLI. Pericytes are cells that surround vascular endothelial cells to reinforce vessel integrity and regulate local blood pressure and metabolism. In the past decade, researchers also found that pericytes may function as stem or progenitor cells in the body, showing the potential to differentiate into several cell types. We investigated the gene expression profiles of pericytes during the early stages of limb ischemia, as well as the alterations in pericyte subpopulations to better understand the behavior of pericytes under ischemic conditions.
Methods
In this study, we used a hindlimb ischemia model to mimic CLI in C57/BL6 mice and explore the role of pericytes in regeneration. To this end, muscle pericytes were isolated at different time points after the induction of ischemia. The phenotypes and transcriptomic profiles of the pericytes isolated at these discrete time points were assessed using flow cytometry and RNA sequencing.
Results
Ischemia triggered proliferation and migration and upregulated the expression of myogenesis-related transcripts in pericytes. Furthermore, the transcriptomic analysis also revealed that pericytes induce or upregulate the expression of a number of cytokines with effects on endothelial cells, leukocyte chemoattraction, or the activation of inflammatory cells.
Conclusions
Our findings provide a database that will improve our understanding of skeletal muscle pericyte biology under ischemic conditions, which may be useful for the development of novel pericyte-based cell and gene therapies.
The distribution pattern of the meiotic machinery in known eukaryotes is most parsimoniously explained by the hypothesis that all eukaryotes are ancestrally sexual. However, this assumption is questioned by preliminary results, in culture conditions. These suggested that Acanthamoeba, an organism considered to be largely asexual, constitutively expresses meiosis genes nevertheless—at least in the lab. This apparent disconnect between the “meiosis toolkit” and sexual processes in Acanthamoeba led to the conclusion that the eukaryotic ancestor is asexual. In this review, the “meiosis toolkit” is rigorously defended, drawing on numerous research articles. Additionally, the claim of constitutive meiotic gene expression is probed in Acanthamoeba via the same transcriptomics data. The results show that the expression of the meiotic machinery is not constitutive in Acanthamoeba as claimed before. Furthermore, it is argued that this would have no implications for understanding the nature of the eukaryotic ancestor, regardless of the result.
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