Sonoda Yoshiaki
Department of iPS Stem Cell Regenerative Medicine, Kansai Medical University.
Rinsho Ketsueki. 2018;59(10):1861-1871. doi: 10.11406/rinketsu.59.1861.
Hematopoietic stem cell (HSC) biology is a current topic of interest having significant implications for clinical HSC transplantation and basic HSC research. It was long believed that the most primitive HSCs in mammals, including those in mice and humans, were CD34 antigen-positive (CD34) cells. However, Nakauchi et al. reported that murine long-term lymphohematopoietic reconstituting HSCs were lineage marker-negative (Lin) c-kitSca-1CD34-low/negative (CD34), known as CD34KSL cells. We have previously identified very primitive human cord blood (CB) -derived CD34-negative (CD34) severe combined immunodeficiency (SCID) -repopulating cells (SRCs) utilizing an intra-bone marrow injection method and have proposed a new concept that CD34SRCs (HSCs) reside at the apex of human HSC hierarchy. Recently, we developed an ultra-high-resolution purification method using the two positive/enrichment markers CD133 and GPI-80 and succeeded in purifying CD34HSCs on a single-cell level. On the basis of these data, we propose a revised roadmap for the commitment of human CD34HSCs. This review updates the concept of the stem cell nature of human CB-derived primitive CD34HSCs.
造血干细胞（HSC）生物学是当前一个备受关注的话题，对临床HSC移植和基础HSC研究具有重要意义。长期以来，人们一直认为包括小鼠和人类在内的哺乳动物中最原始的HSC是CD34抗原阳性（CD34）细胞。然而，中内等人报告称，小鼠长期淋巴造血重建HSC是谱系标记阴性（Lin）c-kitSca-1CD34低/阴性（CD34）细胞，即所谓的CD34KSL细胞。我们之前利用骨髓内注射方法鉴定出了非常原始的人类脐带血（CB）来源的CD34阴性（CD34）严重联合免疫缺陷（SCID）重建细胞（SRC），并提出了一个新的概念，即CD34SRC（HSC）位于人类HSC层级的顶端。最近，我们开发了一种使用两个阳性/富集标记CD133和GPI-80的超高分辨率纯化方法，并成功在单细胞水平上纯化了CD34HSC。基于这些数据，我们提出了人类CD34HSC分化的修订路线图。本综述更新了人类CB来源的原始CD34HSC干细胞性质的概念。
