Human telomerase is regulated by erythropoietin and transforming growth factor-β in human erythroid progenitor cells

Abstract

Telomerase catalytic subunit (hTERT) exerts important cellular functions including telomere homeostasis, genetic stability, cell survival and perhaps differentiation. However, the nature of external or internal signals, which regulate hTERT expression in tissues, remains poorly understood. Thus, whereas it has been described that hTERT gene is regulated along the differentiation of primitive myeloid progenitors, the effect of specific cytokines on telomerase expression in each myeloid lineage is currently unknown. Based on these considerations, we have investigated hTERT expression in erythroid cells treated with erythropoietin (EPO) and transforming growth factor b (TGFb), as putative positive and negative regulators, respectively. We describe here that EPO activates hTERT gene transcription in in vitro-expanded primary erythroid precursors as well as in UT7 erythroleukemia cells. In UT7 cells, this study shows also that EPO acts through a JAK2/STAT5/c-myc axis. In contrast, TGFb blocks EPO signaling downstream of c-myc induction through a Smad3-dependent mechanism. Finally, hTERT appears to be efficiently regulated by EPO and TGFb in an opposite way in erythropoietic cells, arguing for a role of telomerase in red blood cell production.

Lower red blood cell counts in middle‐aged subjects with shorter peripheral blood leukocyte telomere length

“…Next to RBC production, erythropoietin promotes telomerase activity in erythroid progenitor cells (Prade-Houdellier et al, 2007), supporting the relevance of TL maintenance in erythropoiesis. While erythropoietin levels were reported to increase in a healthy, aging population (Kario et al, 1991), at least in men, RBC levels decreased with age in the Asklepios population, suggesting that the reported association between RBC count and TL is independent of erythropoietin.…”

Effect of Recombinant Human Erythropoietin On the Stemness of Bone Marrow-derived Mesenchymal Stem Cells in vitro

“…EPO can also differentiat mouse embryonic stem cells differentiate into cardiomyocytes (5, 7), and also interferes with differentiation of neural stem cells into neural cells (8,20). Following the deep research of EPO, it was found that hTERT mRNA transcription factor was regulated by EPO in vitro cultured erythroid progenitor cells (21). There were experimental results (22) showed that TERT mRNA expression was significantly up regulated in BM CD34…”

Miscreant myeloproliferative disorder stem cells

“…99 This paper suggests that enhanced SPOTLIGHT JAK2 activation may activate hTERT expression and thereby, enhance survival and increase erythroid differentiation of stem cells. 99 Finally, MPD progression to myelofibrosis appears to be associated with an increase in JAK2V617F-expressing HSC 90 as well as overproduction of osteoprotegerin (OPG), which is an essential mediator of osteoblast production. 100 Osteoblasts form an essential component of the HSC niche in the bone marrow microenvironment and thus, increased osteoblast production may enhance the survival of miscreant MPD stem cells returning to the marrow (Figure 1).…”

“…98 A recent report suggested that human telomerase reverse transcriptase (hTERT) known to be involved in regulating telomere length, genomic stability and cell survival may also play a role in EPO-induced red blood cell production. 99 EPO was shown to activate hTERT gene expression through a JAK2/STAT5/c-myc axis. 99 This paper suggests that enhanced SPOTLIGHT JAK2 activation may activate hTERT expression and thereby, enhance survival and increase erythroid differentiation of stem cells.…”

“…99 EPO was shown to activate hTERT gene expression through a JAK2/STAT5/c-myc axis. 99 This paper suggests that enhanced SPOTLIGHT JAK2 activation may activate hTERT expression and thereby, enhance survival and increase erythroid differentiation of stem cells. 99 Finally, MPD progression to myelofibrosis appears to be associated with an increase in JAK2V617F-expressing HSC 90 as well as overproduction of osteoprotegerin (OPG), which is an essential mediator of osteoblast production.…”