造血干细胞和祖细胞上的整合素 α9β1：参与细胞黏附、增殖和分化。
The integrin alpha9beta1 on hematopoietic stem and progenitor cells: involvement in cell adhesion, proliferation and differentiation.
机构信息
University Medical Clinic, Center for Medical Research, Section for Transplantation Immunology and Immunohematology, Waldhörnlestrasse 22, 72072, Tübingen, Germany.
出版信息
Haematologica. 2009 Nov;94(11):1493-501. doi: 10.3324/haematol.2009.006072. Epub 2009 Jul 16.
BACKGROUND
Hematopoietic stem and progenitor cells can interact with their microenvironment via integrins which are adhesion receptors consisting of alpha and beta subunits. Current knowledge suggests that the integrin subunits alpha4 and alpha6 expressed on hematopoietic stem and progenitor cells have distinct roles in retaining stem cells in the bone marrow. The aim of our study was to gain insight into the expression and functions of the integrin subunits alpha7-alpha11 within the endosteal stem cell niche.
DESIGN AND METHODS
Human osteoblasts isolated from trabecular bone and hematopoietic stem and progenitor cells purified from umbilical cord blood or bone marrow aspirates were analyzed for the expression of integrin alpha7-alpha11 chains by reverse transcriptase polymerase chain reaction. The involvement of the integrin alpha9beta1 in hematopoietic stem and progenitor cell adhesion, proliferation and differentiation was analyzed in functional assays.
RESULTS
Transcripts for all investigated integrin chains were found in primary osteoblasts. Highly purified hematopoietic stem and progenitor cells, however, expressed only transcripts encoding integrin subunits alpha7 and alpha9. Flow cytometric analysis verified extracellular expression of the integrin alpha9beta1 on hematopoietic stem and progenitor cells. Cell-cell adhesion assays with osteoblasts and dye-labeled CD34(+) hematopoietic stem and progenitor cells in the presence of function-blocking antibodies revealed a role of integrin alpha9 in hematopoietic stem and progenitor cell adhesion to osteoblasts. Furthermore, the addition of anti-integrin alpha9 antibodies significantly inhibited proliferation and in vitro differentiation of CD34(+) hematopoietic stem and progenitor cells.
CONCLUSIONS
The integrin alpha9beta1 has been identified as a new member of the integrin beta1-subfamily expressed on human hematopoietic stem and progenitor cells. The functional studies strongly suggest that integrin alpha9beta1 contributes to adhesion and differentiation of hematopoietic stem and progenitor cells in the endosteal stem cell niche.
背景
造血干细胞和祖细胞可以通过整合素与其微环境相互作用，整合素是由α和β亚基组成的粘附受体。目前的知识表明，造血干细胞和祖细胞上表达的整合素亚基α4 和α6 在将干细胞保留在骨髓中具有不同的作用。我们的研究旨在深入了解骨内膜干细胞龛中整合素亚基α7-α11 的表达和功能。
设计和方法
通过逆转录聚合酶链反应分析从小梁骨分离的人成骨细胞和从脐带血或骨髓抽吸物纯化的造血干细胞和祖细胞中整合素α7-α11 链的表达。在功能测定中分析整合素α9β1 在造血干细胞和祖细胞粘附、增殖和分化中的作用。
结果
在原代成骨细胞中发现了所有研究的整合素链的转录本。然而，高度纯化的造血干细胞和祖细胞仅表达编码整合素亚基α7 和α9 的转录本。流式细胞术分析证实了造血干细胞和祖细胞上整合素α9β1 的细胞外表达。用成骨细胞和功能阻断抗体标记的 CD34+造血干细胞和祖细胞进行细胞-细胞粘附测定表明整合素α9 在造血干细胞和祖细胞与成骨细胞的粘附中起作用。此外，添加抗整合素α9 抗体显着抑制 CD34+造血干细胞和祖细胞的增殖和体外分化。
结论
整合素α9β1 已被确定为表达于人造血干细胞和祖细胞上的整合素β1 亚家族的新成员。功能研究强烈表明整合素α9β1 有助于骨内膜干细胞龛中造血干细胞和祖细胞的粘附和分化。
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