Huang Tse-Shun, Hsieh Jui-Yu, Wu Yu-Hsuan, Jen Chih-Hung, Tsuang Yang-Hwei, Chiou Shih-Hwa, Partanen Jukka, Anderson Heidi, Jaatinen Taina, Yu Yau-Hua, Wang Hsei-Wei
Institute of Microbiology and Immunology, National Yang-Ming University, No. 155, Sec 2, Li-Nong Street, Taipei 112, Taiwan.
Stem Cells. 2008 May;26(5):1186-201. doi: 10.1634/stemcells.2007-0821. Epub 2008 Feb 28.
Somatic stem cell transplantation holds great promise in regenerative medicine. The best-characterized adult stem cells are mesenchymal stem cells (MSCs), neural stem cells (NSCs), and CD133(+) hematopoietic stem cells (HSCs). The applications of HSCs are hampered since these cells are difficult to maintain in an undifferentiated state in vitro. Understanding genes responsible for stem cell properties and their interactions will help on this issue. The construction of stem cell genetic networks will also help to develop rational strategies to revert somatic cells back to a stem-like state. We performed a systemic study on human CD133(+) HSCs, NSCs, MSCs, and embryonic stem cells and two different progenies of CD133(+) HSCs, microvascular endothelial cells (MVECs) and peripheral blood mononuclear cells. Genes abundant in each or in all three somatic stem cells were identified. We also observed complex genetic networks functioning in postnatal stem cells, in which several genes, such as PTPN11 and DHFR, acted as hubs to maintain the stability and connectivity of the whole genetic network. Eighty-seven HSC genes, including ANGPT1 and GATA2, were independently identified by comparing CD34(+)CD33(-)CD38(-) hematopoietic stem cells with CD34(+) precursors and various matured progenies. Introducing GATA2 into MVECs resulted in dedifferentiation-like transcriptome reprogramming, with HSC genes (such as ANGPT1) being up and endothelial genes (such as EPHB2) being down. This study provides a foundation for a more detailed understanding of human somatic stem cells. Expressing the newly discovered stem cell genes in matured cells might lead to a global reversion of somatic transcriptome to a stem-like status.
体干细胞移植在再生医学领域极具前景。特征最明确的成体干细胞是间充质干细胞（MSC）、神经干细胞（NSC）和CD133(+)造血干细胞（HSC）。由于这些细胞在体外难以维持未分化状态，HSC的应用受到了阻碍。了解负责干细胞特性及其相互作用的基因将有助于解决这一问题。构建干细胞遗传网络也将有助于制定合理策略，使体细胞恢复到类似干细胞的状态。我们对人CD133(+) HSC、NSC、MSC和胚胎干细胞以及CD133(+) HSC的两种不同子代，即微血管内皮细胞（MVEC）和外周血单个核细胞进行了系统研究。确定了在每种或所有三种体干细胞中丰富的基因。我们还观察到在出生后干细胞中起作用的复杂遗传网络，其中几个基因，如PTPN11和DHFR，充当枢纽以维持整个遗传网络的稳定性和连通性。通过将CD34(+)CD33(-)CD38(-)造血干细胞与CD34(+)前体细胞和各种成熟子代进行比较，独立鉴定出87个HSC基因，包括ANGPT1和GATA2。将GATA2导入MVEC导致类似去分化的转录组重编程，HSC基因（如ANGPT1）上调，内皮基因（如EPHB2）下调。这项研究为更详细地了解人体干细胞提供了基础。在成熟细胞中表达新发现的干细胞基因可能导致体细胞转录组全面恢复到类似干细胞的状态。
