Critical role of long non-coding RNAs in excessive erythropoietic response in Monge's disease

Abstract

Excessive erythrocytosis (EE) is a major hallmark of patients suffering from chronic mountain sickness (CMS, Monge’s disease) and is responsible for major morbidity and even mortality in early adulthood. We took advantage of unique populations, one living at high altitude (Peru) showing EE, while another population, at the same altitude and region, shows no evidence of EE (non-CMS). We have built an in-vitro human iPS-derived model system to study the genetic and epigenetic mechanisms related to pathology of excessive erythropoetic response in these Monge's disease patients. Through RNA-seq, we identified and validated the function of a group of long non-coding RNA (lncRNAs) that regulate erythropoiesis in Monge’s disease. Among the lncRNAs, we found that LINC02228 specifically played a critical role in erythropoiesis the CMS cells and non-CMS based on our functional assays in our in-vitro model systems. We observed that LINC02228 has a huge impact on erythriod colony production (>50% reduction in colonies p<0.001 with the control vs LINC02228-KD). Furthermore, we have also assessed the downstream target genes for these lncRNA (Eg. CSNK2B) and mechanism(s) of erythropoetic regulation by these lncRNAs and found an important role and mediation of erythropoetic transcriptional factor GATA1. We conclude that LINC02228 mediate erythropoesis in Monge's diseases through critical downstream effectors (CSNK2B and GATA1). NIH This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.