CD109 is expressed on a subpopulation of CD34+ cells enriched in hematopoietic stem and progenitor cells
CD109 is expressed on a subpopulation of CD34+ cells enriched in hematopoietic stem and progenitor cells
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DOI：
10.1016/s0301-472x(99)00071-5
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发表时间：
1999-08-01
影响因子：
2.6
通讯作者：
Sutherland, DR
中科院分区：
文献类型：
--
作者：
Murray, LJ;Bruno, E;Sutherland, DR
CD 109是一种170 kD的单体细胞表面糖蛋白，表达于内皮细胞、活化但不静息的T淋巴细胞、活化但不静息的血小板、白血病巨核细胞和骨髓CD 34（+）细胞亚群上。观察CD 109表达和巨核细胞谱系（MK）之间的明显关联，我们试图确定CD 109是否在MK祖细胞上表达。在胚胎骨髓（FBM）中，MK祖细胞的丰富来源，CD 109在平均11%的CD 34（+）细胞上表达。FBM CD 34（+）细胞分为CD 109（+）和CD 109（-）部分的荧光激活细胞分选（FACS）显示，CD 34（+）CD 109（+）亚群包含几乎所有可测定的MK祖细胞，包括集落形成单位-MK（CFU-MK）和更原始的爆发形成单位-MK（BFU-MK）。CD 34（+）CD 109（+）亚群还包含所有可测定的红系爆发形成单位（BFU-E）、90%的粒细胞/巨噬细胞集落形成单位（CFU-GM）和所有更原始的混合谱系集落形成单位（CFU-mix）。相反，FBM、成人骨髓（ABM）和精氨酸动员的外周血（MPB）中的CD 34（+）CD 109（-）细胞的表型分析表明，该亚群包含淋巴定向祖细胞，主要是B细胞谱系。CD 109在最亮的CD 34（+）细胞上表达，不仅在FBM中可识别，而且在ABM和MPB中也可识别，这表明最原始的候选造血干细胞（HSC）也可能包含在CD 109（+）亚群中。在FBM CD 34（+）细胞的长期骨髓培养中，所有可测定的鹅卵石区形成细胞（CAFC）活性均包含在CD 109（+）细胞亚群中。对ABM中CD 34（+）CD 109（+）部分的进一步表型分析表明，该亚群包括候选HSC，其CD 38染色较差，但表达Thy-1（CD 90）和AC 133抗原，并流出线粒体染料Rhodamine 123（Rho 123）。当选择的CD 34（+）细胞进行CD 109表达和Rho 123染色分选时，几乎所有的CAFC活性都在Rho 123染色最差的CD 109（+）部分中发现。CD 34（+）细胞也被分选为Thy-1（+）CD 109（+）和Thy-1（-）CD 109（+）部分，并且几乎所有的CAFC活性都在Thy 1（+）CD 109（+）亚群中发现。相比之下，Thy-1（-）CD 109（+）组分包含大部分短期集落形成细胞（CFC）活性。因此，CD 109是在CD 34（+）细胞亚群上表达的抗原，所述亚群包括多能HSC以及所有类型的MK和骨髓红系祖细胞。与Thy-1结合，CD 109可用于从候选HSC中鉴定和分离骨髓-红细胞和所有类别的MR祖细胞。(C)1999年国际实验血液学学会。出版社：Elsevier Science Inc.
CD109 is a monomeric cell surface glycoprotein of 170 kD that is expressed on endothelial cells, activated but not resting T-lymphocytes, activated but not resting platelets, leukemic megakaryoblasts, and a subpopulation of bone marrow CD34(+) cells. Observing an apparent association between CD109 expression and the megakaryocyte lineage (MK), we sought to determine whether CD109 was expressed on MK progenitors. In fetal bone marrow (FBM), a rich source of MK progenitors, CD109 is expressed on a mean of 11% of CD34(+) cells. Fluorescence activated cell sorting (FACS) of FBM CD34(+) cells into CD109(+) and CD109(-) fractions revealed that the CD34(+)CD109(+) subset contained virtually all assayable MK progenitors, including the colony-forming unit-MK (CFU-MK) and the more primitive burst-forming unit-MK (BFU-MK). The CD34(+)CD109(+) subset also contained all the assayable burst-forming units-erythroid (BFU-E), 90% of the colony-forming units-granulocyte/macrophage (CFU-GM), and all of the more primitive mixed lineage colony-forming units (CFU-mix). In contrast, phenotypic analysis of the CD34(+)CD109(-) cells in FBM, adult bone marrow (ABM) and cytokine-mobilized peripheral blood (MPB) demonstrated that this subset comprises lymphoid-committed progenitors, predominantly of the B-cell lineage. CD109 was expressed on the brightest CD34(+) cells identifiable not only in FBM, but also in ABM and MPB indicating that the most primitive, candidate hematopoietic stem cells (HSC) might also be contained in the CD109(+) subset. In long-term marrow cultures of FBM CD34(+) cells, all assayable cobblestone area forming cell (CAFC) activity was contained within the CD109(+) cell subset. Further phenotypic analysis of the CD34(+)CD109(+) fraction in ABM indicated that this subset included candidate HSCs that stain poorly with CD38, but express Thy-1 (CD90) and AC133 antigens, and efflux the mitochondrial dye Rhodamine 123 (Rho123). When selected CD34(+) cells were sorted for CD109 expression and Rho123 staining, virtually all CAFC activity was found in the CD109(+) fraction that stained most poorly with Rho123. CD34(+) cells were also sorted into Thy-1(+)CD109(+) and Thy-1(-)CD109(+) fractions and virtually all the CAFC activity was found in the Thy1(+)CD109(+) subset. In contrast, the Thy-1(-)CD109(+) fraction contained most of the short-term colony-forming cell (CFC) activity. CD109, therefore, is an antigen expressed on a subset of CD34(+) cells that includes pluripotent HSCs as well as all classes of MK and myeloerythroid progenitors. In combination with Thy-1, CD109 can be used to identify and separate myelo-erythroid and all classes of MR progenitors from candidate HSCs. (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc.