Comprehensive transcriptome analysis of erythroid differentiation potential of olive leaf in haematopoietic stem cells

Abstract

Anaemia is one of the leading causes of disability in young adults and is associated with increased morbidity and mortality in elderly. With a global target to reduce the disease burden of anaemia, recent researches focus on novel compounds with the ability to induce erythropoiesis and regulate iron homeostasis. We aimed to explore the biological events and potential polypharmacological effects of water‐extracted olive leaf (WOL) on human bone marrow–derived haematopoietic stem cells (hHSCs) using a comprehensive gene expression analysis. HPLC analysis identifies six bioactive polyphenols in the WOL. Treatment with WOL for 12 days regulated gene expressions related to erythroid differentiation, oxygen homeostasis, iron homeostasis, haem metabolism and Hb biosynthesis in hHSCs. Functional clustering analysis reveals several major functions of WOL such as ribosomal biogenesis and mitochondrial translation machinery, glycolytic process, ATP biosynthesis and immune response. Additionally, the colonies of both primitive and mature erythroid progenitors, CFU‐E and BFU‐E, were significantly increased in WOL‐treated hHSCs. The expressions of erythroid markers, CD47, glycophorin A (GYPA), and transferrin receptor (TFRC) and adult Hb subunits‐HBA and HBB were also confirmed in immunofluorescent staining and flow cytometer analysis in WOL‐treated hHSCs. It is well known that induction of lineage‐specific differentiation, as well as the maturation of early haematopoietic precursors into fully mature erythrocytes, involves multiple simultaneous biological events and complex signalling networks. In this regard, our genome‐wide transcriptome profiling with microarray study on WOL‐treated hHSCs provides general insights into the multitarget prophylactic and/or therapeutic potential of WOL in anaemia and other haematological disorders.

Saracatinib prompts hemin-induced K562 erythroid differentiation but suppresses erythropoiesis of hematopoietic stem cells

“…The erythroid maturation markers and HBG expression were induced by hemin treatment in K562 cells [ 23 ]. This cell model has already been used in drug screening [ 24 ] and in the study of the molecular mechanisms of cell development [ 25 ], as K562 cells share a similar pathway of erythroid cell development with HSCs. However, the difference between normal and malignant hematopoietic cells is due to the mRNA expression profile [ 26 ].…”

Hematinic Potential of Olive Leaf Extract: Evidence from an In Vivo Study in Mice and a Pilot Study in Healthy Human Volunteers

“…Olive leaves were collected from a farm in Tunisia in mid-December 2018 as described in a previous study [22]. These leaves were naturally air-dried in the shade at a temperature ranging from 20 to 25 • C. The dried leaves were then processed into powder form using a food processor.…”

“…The HPLC analysis for apigenin (A), luteolin (L), hydroxytyrosol (HT), oleuropein (OP), A7G, and L7G was carried out using a Shimadzu Prominence LC-20 system as previously reported [22]. The HPLC column was ZORBAX SB-C18 (5 µm, ϕ 4.6 × 150 mm).…”

“…After 24 h, the cells were treated with 120 µg/mL WOL and its eight components-A, A7G, A7R, HT, luteolin L, L7G, OP, and OS. The concentration of WOL used for treating the K562 cells (120 µg/mL) was established based on the concentration utilized in a previous study that investigated the induction of erythroid differentiation [22]. The treatment concentration of these eight components was decided based on their respective dry weight in 120 µg/mL WOL (OP: 35.36 µM, OS: 5.23 µM, HT: 2.79 µM, A: 0.31 µM, A7G: 0.49 µM, A7R: 2.26 µM, L: 0.66 µM, and L7G: 8.19 µM).…”

“…On the other hand, two other components of OLE, namely apigenin 7-glucoside (A7G) and luteolin 7-glucoside (L7G), have been reported to induce human hematopoietic stem cells (hHSCs) differentiation into the erythroid lineage [21]. Furthermore, in hHSCs, the aqueous extract of olive leaves (WOL) induced erythroid differentiation and contributed to oxygen and iron homeostasis, heme metabolism, and hemoglobin biosynthesis [22].…”