Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, AMMS, Beijing, People's Republic of China.
Stem Cells. 2019 Oct;37(10):1319-1330. doi: 10.1002/stem.3053. Epub 2019 Aug 14.
Hematopoietic stem (HSC) and progenitor (HPC) cells are regulated by interacting signals and cellular and noncellular elements of the hematopoietic niche. We previously showed that CD166 is a functional marker of murine and human HSC and of cellular components of the murine niche. Selection of murine CD166 engrafting HSC enriched for marrow repopulating cells. Here, we demonstrate that CD166-CD166 homophilic interactions enhance generation of murine and human HPC in vitro and augment hematopoietic function of these cells. Interactions between cultured CD166 Lineage Sca-1 c-Kit (LSK) cells and CD166 osteoblasts (OBs) significantly enhanced the expansion of colony-forming units (CFUs). Interactions between CD166 LSK cells and immobilized CD166 protein generated more CFU in short-term cultures than between these cells and bovine serum albumin (BSA) or in cultures initiated with CD166 LSK cells. Similar results were obtained when LSK cells from wildtype (WT) or CD166 knockout (KO) (CD166 ) mice were used with immobilized CD166. Human cord blood CD34 cells expressing CD166 produced significantly higher numbers of CFUs following interaction with immobilized CD166 than their CD166 counterparts. These data demonstrate the positive effects of CD166 homophilic interactions involving CD166 on the surface of murine and human HPCs. Single-cell RNA-seq analysis of CD150 CD48 (signaling lymphocyte activation molecule (SLAM)) LSK cells from WT and CD166 mice incubated with immobilized CD166 protein revealed that engagement of CD166 on these cells activates cytokine, growth factor and hormone signaling, epigenetic pathways, and other genes implicated in maintenance of stem cell pluripotency-related and mitochondria-related signaling pathways. These studies provide tangible evidence implicating CD166 engagement in the maintenance of stem/progenitor cell function. Stem Cells 2019;37:1319-1330.
造血干（HSC）和祖（HPC）细胞受相互作用的信号以及造血龛的细胞和非细胞成分调节。我们之前表明，CD166 是小鼠和人类 HSC 以及小鼠龛的细胞成分的功能标志物。选择表达 CD166 的小鼠嵌合 HSC 可富集骨髓重植细胞。在这里，我们证明 CD166-CD166 同型相互作用增强了体外小鼠和人类 HPC 的生成，并增强了这些细胞的造血功能。培养的 CD166 谱系 Sca-1 c-Kit（LSK）细胞与 CD166 成骨细胞（OBs）之间的相互作用显著增强了集落形成单位（CFUs）的扩增。与这些细胞与牛血清白蛋白（BSA）或与 LSK 细胞起始的培养物相比，CD166 LSK 细胞与固定化 CD166 蛋白之间的相互作用在短期培养物中产生了更多的 CFU。当使用固定化 CD166 时，来自野生型（WT）或 CD166 敲除（KO）（CD166 ）小鼠的 LSK 细胞也获得了类似的结果。表达 CD166 的人脐血 CD34 细胞与固定化 CD166 相互作用后产生的 CFU 数量明显高于其 CD166 对应物。这些数据表明，涉及 CD166 表面的 CD166 同型相互作用对小鼠和人类 HPC 具有积极影响。用固定化 CD166 孵育 WT 和 CD166 小鼠的 CD150 CD48（信号淋巴细胞激活分子（SLAM））LSK 细胞的单细胞 RNA-seq 分析表明，这些细胞上 CD166 的结合激活了细胞因子、生长因子和激素信号、表观遗传途径以及其他与维持干细胞多能性相关和与线粒体相关的信号途径相关的基因。这些研究提供了确凿的证据，表明 CD166 的结合参与了维持干细胞/祖细胞功能。干细胞 2019;37:1319-1330。
