Szalayova, I. | bioRxiv Science

bioRxiv2024

Osteocyte-derived erythroferrone regulates liver hepcidin during stress erythropoiesis

Our knowledge of which bone marrow cells affect red cell production is still incomplete. To explore the role of osteocytes in the process we performed bulk RNAseq of osteocytes isolated from control and phlebotomized mice. The top-upregulated gene following phlebotomy was Fam132b, erythroferrone (Erfe). Erfe expression in osteocytes was also upregulated after erythropoietin (EPO) treatment and hypoxia in vitro. To explore if osteocytes contribute to the systemic ERFE levels, we generated two mouse models. We first transplanted wild-type BM in Erfe-/- mice creating a model where ERFE is produced in the BM but not by osteocytes. After phlebotomy, liver hepcidin suppression was significantly lower in mice where the osteocytes could not produce ERFE. To confirm that osteocytes are responsible for this difference, we generated mice lacking EPO receptors in osteocytes by crossing Eporflox/flox and Dmp1-Cre mice. After phlebotomy, these mice showed reduced hepcidin suppression in the liver and higher circulating serum hepcidin levels compared to controls. Our work identified a novel function of osteocytes in suppressing systemic hepcidin levels during stress erythropoiesis.

immunology↗

bioRxiv2022

SARS-CoV-2 entry sites are present in all structural elements of the human glossopharyngeal and vagal nerves: clinical implications

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infections result in the temporary loss of smell and taste (anosmia and dysgeusia) in about one third of confirmed cases. Several investigators have reported that the viral spike protein receptor is present in olfactory neurons. However, no study has been published to date showing the presence of viral entry sites angiotensin-converting enzyme 2 (ACE2), neuropilin1 (NRP1), and TMPRSS2, the serine protease necessary for priming the viral proteins, in human nerves that are responsible for taste sensation (cranial nerves: VII, IX and X). We used immunocytochemistry to examine three postmortem donor samples of the IXth (glossopharyngeal) and Xth (vagal) cranial nerves where they leave/join the medulla from three donors to confirm the presence of ACE2, NRP1 and TMPRSS2. Two samples were paraffin embedded; one was a frozen sample. In addition to staining sections from the latter, we isolated RNA from it, made cDNA, and performed PCR to confirm the presence of the mRNAs that encode the proteins visualized. All three of the proteins required for SARS-CoV-2 infections appear to be present in the human IXth and Xth nerves near the medulla. Direct infection of these nerves by the COVID-19 virus is likely to cause the loss of taste experienced by many patients. In addition, potential viral spread through these nerves into the adjacent brainstem respiratory centers might also aggravate the respiratory problems patients are experiencing.

neuroscience↗