title: Transdifferentiation of Human Hair Follicle Mesenchymal Stem Cells into Red Blood Cells by OCT4.
abstract: Shortage of red blood cells (RBCs, erythrocytes) can have potentially life-threatening consequences for rare or unusual blood type patients with massive blood loss resulting from various conditions. Erythrocytes have been derived from human pluripotent stem cells (PSCs), but the risk of potential tumorigenicity cannot be ignored, and a majority of these cells produced from PSCs express embryonic ε- and fetal γ-globins with little or no adult β-globin and remain nucleated. Here we report a method to generate erythrocytes from human hair follicle mesenchymal stem cells (hHFMSCs) by enforcing OCT4 gene expression and cytokine stimulation. Cells generated from hHFMSCs expressed mainly the adult β-globin chain with minimum level of the fetal γ-globin chain. Furthermore, these cells also underwent multiple maturation events and formed enucleated erythrocytes with a biconcave disc shape. Gene expression analyses showed that OCT4 regulated the expression of genes associated with both pluripotency and erythroid development during hHFMSC transdifferentiation toward erythroid cells. These findings show that mature erythrocytes can be generated from adult somatic cells, which may serve as an alternative source of RBCs for potential autologous transfusion.
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, Department of Pathology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Avenue, Changchun 130021, China.
authors.forename: Zhijing
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Advanced Cell Technology, 33 Locke Drive, Marlborough, MA 01752, USA.
authors.forename: Shi-Jiang
authors.initials: SJ
authors.lastname: Lu
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, Department of Pathology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Avenue, Changchun 130021, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Key Laboratory of Biotechnology and Pharmaceutical Engineering, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Tan
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, Department of Pathology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Avenue, Changchun 130021, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, Department of Pathology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Avenue, Changchun 130021, China.
authors.forename: Minlan
authors.initials: M
authors.lastname: Yang
authors.affiliation: Morphology Center of Hematology Department, Cancer Center, the First Clinical Hospital of Jilin University, Changchun 130000, China.
authors.forename: Fuming
authors.initials: F
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, Department of Pathology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Avenue, Changchun 130021, China.
authors.forename: Yulin
authors.identifier: 0000-0002-3758-7568
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, Department of Pathology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Avenue, Changchun 130021, China.
authors.forename: Chengshi
authors.initials: C
authors.lastname: Quan