SummaryAlthough the mammalian heart is one of the least regenerative organs in the body, recent evidence indicates that the myocardium undergoes a certain degree of renewal to maintain homeostasis during normal aging. However, the cellular origin of cardiomyocyte renewal has remained elusive due to lack of lineage tracing experiments focusing on putative adult cardiac precursor cells. We have generated triple-transgenic mice based on the tet-cre system to identify descendants of cells that have expressed the stem cell marker Sca1. We found a significant and lasting contribution of Sca1-derived cells to cardiomyocytes during normal aging. Ischemic damage and pressure overload resulted in increased differentiation of Sca1-derived cells to the different cell types present in the heart. Our results reveal a source of cells for cardiomyocyte renewal and provide a possible explanation for the limited contribution of Sca1-derived cells to myocardial repair under pathological conditions.

Currently, few evidences have shown the possible involvement of autoimmunity in patients affected by coronavirus disease 2019 (COVID‐19). In this study, we elucidate whether severe acute respiratory syndrome coronavirus disease 2 (SARS‐CoV‐2) stimulates autoantibody production and contributes to autoimmunity activation. We enrolled 40 adult patients (66.8 years mean age) admitted to Alessandria Hospital between March and April 2020. All the patients had a confirmed COVID‐19 diagnosis and no previously clinical record of autoimmune disease. Forty blood donors were analyzed for the same markers and considered as healthy controls. Our patients had high levels of common inflammatory markers, such as C reactive protein, lactate dehydrogenase, ferritin, and creatinine. Interleukin‐6 concentrations were also increased, supporting the major role of this interleukin during COVID‐19 infection. Lymphocyte numbers were generally lower compared with healthy individuals. All the patients were also screened for the most common autoantibodies. We found a significant prevalence of antinuclear antibodies, antineutrophil cytoplasmic antibodies, and ASCA immunoglobulin A antibodies. We observed that patients having a de novo autoimmune response had the worst acute viral disease prognosis and outcome. Our results sustain the hypothesis that COVID‐19 infection correlates with the autoimmunity markers. Our study might help clinicians to: (a) better understand the heterogeneity of this pathology and (b) correctly evaluate COVID‐19 clinical manifestations. Our data explained why drugs used to treat autoimmune diseases may also be useful for SARS‐CoV‐2 infection. In addition, we highly recommend checking patients with COVID‐19 for autoimmunity markers, mainly when deciding on whether to treat them with plasma transfer therapy. WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? ☑ Recent data sustain the idea that autoimmune phenomena exist in patients with coronavirus disease 2019 (COVID‐19), but other investigations are necessary to define the possible link between severe acute respiratory syndrome coronavirus disease 2 (SARS‐CoV‐2) infection and autoimmune disease onset. WHAT QUESTION DID THIS STUDY ADDRESS? ☑ In this monocentric study, we demonstrated how SARS‐CoV‐2 infection could be associated with an autoimmune response and development of autoantibodies. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? ☑ Patients with COVID‐19 having an increased level of inflammatory markers and strong autoantibodies positivity (i.e., antinuclear antibodies and antineutrophil cytoplasmic antibodies) presented the worst clinical outcome. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? ☑ These results suggest that the drugs normally used to treat autoimmune diseases should also be considered during SARS‐CoV‐2, improving public health. In addition, before starting a transfer plasma therapy, it is important to also evaluate the autoimmunity conditions of the patients with COVID‐19. Transferring antibodies or trying to neutrali...

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Muscle satellite cells are indispensable for muscle regeneration, but the functional diversity of their daughter cells is unknown. Here, we show that many Pax7+MyoD− cells locate both beneath and outside the basal lamina during myofiber maturation. A large majority of these Pax7+MyoD− cells are not self-renewed satellite cells, but have different potentials for both proliferation and differentiation from Pax7+MyoD+ myoblasts (classical daughter cells), and are specifically marked by expression of the doublecortin (Dcx) gene. Transplantation and lineage-tracing experiments demonstrated that Dcx-expressing cells originate from quiescent satellite cells and that the microenvironment induces Dcx in myoblasts. Expression of Dcx seems to be necessary for myofiber maturation because Dcx-deficient mice exhibited impaired myofiber maturation resulting from a decrease in the number of myonuclei. Furthermore, in vitro and in vivo studies suggest that one function of Dcx in myogenic cells is acceleration of cell motility. These results indicate that Dcx is a new marker for the Pax7+MyoD− subpopulation, which contributes to myofiber maturation during muscle regeneration.

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