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Comprehensive transcriptome analysis of erythroid differentiation potential of olive leaf in haematopoietic stem cells
Authors:Shinji Kondo  Farhana Ferdousi  Ken Yamauchi  Sofya Suidasari  Miki Yokozawa  Mohamed Moncef Harrabi  Ken-ichi Tominaga  Hiroko Isoda
Affiliation:1. R&D Center for Tailor-Made QOL, University of Tsukuba, Tsukuba, Japan

Contribution: Data curation (equal), Formal analysis (equal), ​Investigation (equal), Validation (equal), Visualization (equal), Writing - original draft (equal);2. Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Japan

AIST-University of Tsukuba Open innovation laboratory for food and medicinal resource engineering (FoodMed-OIL), University of Tsukuba, Tsukuba, Japan

Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan

Contribution: Data curation (equal), Formal analysis (equal), ​Investigation (equal), Validation (equal), Visualization (equal), Writing - original draft (equal);3. Nutrition Act Co., Ltd., Tokyo, Japan

Contribution: Resources (lead);4. Nutrition Act Co., Ltd., Tokyo, Japan

Contribution: Resources (supporting);5. Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Japan

Contribution: Resources (lead);6. AIST-University of Tsukuba Open innovation laboratory for food and medicinal resource engineering (FoodMed-OIL), University of Tsukuba, Tsukuba, Japan

Contribution: Data curation (supporting), Formal analysis (supporting), ​Investigation (supporting);7. R&D Center for Tailor-Made QOL, University of Tsukuba, Tsukuba, Japan

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.
Keywords:anaemia  DNA microarray  erythropoiesis  haematopoietic stem cell  iron homeostasis  olive leaf
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