Multiparameter Analysis of Human Bone Marrow Stromal Cells Identifies Distinct Immunomodulatory and Differentiation-Competent Subtypes.
Multiparameter Analysis of Human Bone Marrow Stromal Cells Identifies Distinct Immunomodulatory and Differentiation-Competent Subtypes.
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DOI：
10.1016/j.stemcr.2015.05.005
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发表时间：
2015-06-09
影响因子：
5.9
通讯作者：
Genever, Paul
中科院分区：
文献类型：
--
作者：
James, Sally;Fox, James;Afsari, Farinaz;Lee, Jennifer;Clough, Sally;Knight, Charlotte;Ashmore, James;Ashton, Peter;Preham, Olivier;Hoogduijn, Martin;Ponzoni, Raquel De Almeida Rocha;Hancock, Y.;Coles, Mark;Genever, Paul
骨髓基质细胞（BMSCs，也称为骨髓间充质基质细胞）提供造血支持和免疫调节，并含有能够分化成骨的干细胞部分。我们使用永生化人骨髓间充质干细胞无性系对骨髓间充质干细胞亚群的功能标记进行多层次分析。所有克隆均表达典型的BMSC细胞表面抗原；然而，具有三龄分化能力的克隆具有增强的血管相互作用基因集，而非分化克隆具有独特的CD317阳性，具有显著丰富的免疫调节转录网络和高IL-7产生。IL-7谱系追踪和CD317免疫定位证实了一种罕见的非分化BMSC亚型的存在，不同于体内的Cxcl12-DsRed+血管周围基质细胞。集落形成的CD317+ IL-7hi细胞，在异质人BMSC组分中鉴定出约1%-3%的频率，使用拉曼光谱发现与非分化BMSC克隆具有相同的生物分子特征。骨髓间充质干细胞亚群具有不同的功能特征，可能在免疫控制、淋巴生成和骨稳态中具有特定的作用。永生化的BMSC克隆用于深入的功能和生物物理分析，定义了不同的分化能力和不分化能力的BMSC亚群，三龄的BMSC克隆表现出增强的血管相互作用基因集，一种非分化的，“免疫启动的”CD317+/IL-7hi BMSC亚群在体内被鉴定出来，Genever和同事使用永生化的人骨髓基质细胞（BMSC）克隆进行了深入的亚型变异分析。他们发现了一种罕见的，集落形成的BMSC亚型，缺乏典型的三期分化能力，在基础条件下显示出显著的免疫调节基因集，在体外和体内具有高IL-7和CD317表达。
Bone marrow stromal cells (BMSCs, also called bone-marrow-derived mesenchymal stromal cells) provide hematopoietic support and immunoregulation and contain a stem cell fraction capable of skeletogenic differentiation. We used immortalized human BMSC clonal lines for multi-level analysis of functional markers for BMSC subsets. All clones expressed typical BMSC cell-surface antigens; however, clones with trilineage differentiation capacity exhibited enhanced vascular interaction gene sets, whereas non-differentiating clones were uniquely CD317 positive with significantly enriched immunomodulatory transcriptional networks and high IL-7 production. IL-7 lineage tracing and CD317 immunolocalization confirmed the existence of a rare non-differentiating BMSC subtype, distinct from Cxcl12-DsRed+ perivascular stromal cells in vivo. Colony-forming CD317+ IL-7hi cells, identified at ∼1%–3% frequency in heterogeneous human BMSC fractions, were found to have the same biomolecular profile as non-differentiating BMSC clones using Raman spectroscopy. Distinct functional identities can be assigned to BMSC subpopulations, which are likely to have specific roles in immune control, lymphopoiesis, and bone homeostasis. Immortalized BMSC clones were generated for in-depth functional and biophysical analysis Distinct differentiation-competent and incompetent BMSC subsets are defined Trilineage-competent BMSC clones exhibit enhanced vascular interaction gene sets A non-differentiating, “immune-primed,” CD317+/IL-7hi BMSC subset was identified in vivo Genever and colleagues used immortalized human bone marrow stromal cell (BMSC) clones for in-depth analysis of subtype variation. They identified a rare, colony-forming BMSC subtype that lacked typical trilineage differentiation capacity, which under basal conditions displayed a marked immunomodulatory gene set, with high IL-7 and CD317 expression in vitro and in vivo.
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影响因子：
5.9
作者：
Mabuchi, Yo;Morikawa, Satoru;Harada, Seiko;Niibe, Kunimichi;Suzuki, Sadafumi;Renault-Mihara, Francois;Houlihan, Diarmaid D.;Akazawa, Chihiro;Okano, Hideyuki;Matsuzaki, Yumi
通讯作者：
Matsuzaki, Yumi
影响因子：
3.8
作者：
Russell, Katie C.;Lacey, Michelle R.;Gilliam, Jennifer K.;Tucker, H. Alan;Phinney, Donald G.;OConnor, Kim C.
通讯作者：
OConnor, Kim C.
影响因子：
23.9
作者：
Zhou, Bo O.;Yue, Rui;Murphy, Malea M.;Peyer, James G.;Morrison, Sean J.
通讯作者：
Morrison, Sean J.
影响因子：
3.4
作者：
Chan, JW;Taylor, DS;Huser, T
通讯作者：
Huser, T
影响因子：
64.5
作者：
Sacchetti, Benedetto;Funari, Alessia;Bianco, Paolo
通讯作者：
Bianco, Paolo