Department of Pathology, Mackay Memorial Hospital, Taipei, Taiwan.
Taiwan J Obstet Gynecol. 2009 Dec;48(4):356-69. doi: 10.1016/S1028-4559(09)60324-7.
Somatic CD34+ CD38- stem cells can differentiate into cells of hematopoietic and endothelial lineages and have been clinically used to treat diseases. These stem cells can be obtained from cord blood (CB), bone marrow or granulocyte-macrophage colony-stimulating factor-mobilized peripheral blood. Unmasking genes differentially expressed in hematopoietic stem cells (HSCs) from different anatomic locations can improve our understanding of their basic biological features and help in clinical decision making when applying different HSCs.
We performed microarray analysis on human CD34+ CD38- HSCs isolated from CB, bone marrow and peripheral blood. Systems biology and advanced bioinformatics tools were used to better understand the biological modules and genetic networks accompanying each HSC subtype.
We identified HSC genes differentially expressed in various HSCs and found them to be involved in critical biological processes such as cell cycle regulation, cell motility, and endogenous antigen presentation. Among these three HSC types, HSCs from CB expressed the fewest rejection and immune response-associated genes, thereby showing the best potential as a transplantation source. Analysis of HSC-enriched genes using systems biology tools revealed a complex genetic network functioning in different CD34+ CD38- cells, in which several genes act as hubs, such as MYC in CB HSCs and hepatic growth factor in bone marrow HSCs, to maintain the stability or connectivity of the whole network.
This study provides the foundation for a more detailed understanding of CD34+ CD38- HSCs from different sources, and reveals the potentials of different HSCs for different clinical applications.
体干细胞 CD34+ CD38- 可以分化为造血和内皮谱系的细胞,已临床用于治疗疾病。这些干细胞可以从脐带血(CB)、骨髓或粒细胞巨噬细胞集落刺激因子动员的外周血中获得。揭示不同解剖部位造血干细胞(HSCs)中差异表达的基因,可以增进我们对其基本生物学特征的理解,并有助于在应用不同 HSCs 时做出临床决策。
我们对从 CB、骨髓和外周血中分离出的人 CD34+ CD38- HSCs 进行了微阵列分析。系统生物学和先进的生物信息学工具用于更好地理解伴随每个 HSC 亚型的生物学模块和遗传网络。
我们鉴定了不同 HSCs 中差异表达的 HSC 基因,并发现它们参与了关键的生物学过程,如细胞周期调控、细胞迁移和内源性抗原呈递。在这三种 HSC 类型中,CB 来源的 HSCs 表达的排斥和免疫反应相关基因最少,因此作为移植来源具有最佳潜力。使用系统生物学工具对 HSC 富集基因进行分析,揭示了不同 CD34+ CD38- 细胞中复杂的遗传网络,其中一些基因作为枢纽发挥作用,如 CB HSCs 中的 MYC 和骨髓 HSCs 中的肝生长因子,以维持整个网络的稳定性或连通性。
本研究为更详细地了解来自不同来源的 CD34+ CD38- HSCs 奠定了基础,并揭示了不同 HSCs 在不同临床应用中的潜力。