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

• Published in: Journal of cellular and molecular medicine Vol. 25; no. 15; pp. 7229 - 7243
• Main Authors: Kondo, Shinji, Ferdousi, Farhana, Yamauchi, Ken, Suidasari, Sofya, Yokozawa, Miki, Harrabi, Mohamed Moncef, Tominaga, Ken‐ichi, Isoda, Hiroko
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.08.2021; John Wiley and Sons Inc
• Subjects: anaemia; Anemia; Apoptosis; Biosynthesis; Blood transfusions; Bone marrow; CD47 Antigen - metabolism; Cell growth; Cells, Cultured; DNA microarray; DNA microarrays; Erythrocytes; Erythropoiesis; Food fortification; Gene expression; Genomes; Glycolysis; Glycophorins - metabolism; haematopoietic stem cell; Hematological diseases; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - metabolism; Hemoglobins - metabolism; High-performance liquid chromatography; Homeostasis; Humans; Immune response; Iron; iron homeostasis; K562 Cells; Leaves; Leukemia; Mitochondria; Morbidity; Morphology; Olea - chemistry; olive leaf; Original; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Leaves - chemistry; Polyphenols; Progenitor cells; Receptors, Transferrin - metabolism; Software; Stem cells; Transcriptome; Transcriptomes; Transferrin; Young adults; DNA microarray; anaemia; olive leaf; erythropoiesis; iron homeostasis; haematopoietic stem cell
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.16752

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.