Impact of interactions of cellular components of the bone marrow microenvironment on hematopoietic stem and progenitor cell function
Impact of interactions of cellular components of the bone marrow microenvironment on hematopoietic stem and progenitor cell function
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DOI：
10.1182/blood-2009-09-246173
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发表时间：
2010-04-22
期刊：
影响因子：
20.3
通讯作者：
Srour, Edward F.
中科院分区：
文献类型：
--
作者：
Chitteti, Brahmananda R.;Cheng, Ying-Hua;Srour, Edward F.
造血干细胞（HSC）和祖细胞（HPC）的命运是由内在和外在参数。我们通过分析成骨细胞（OB）和基质细胞（SC）对谱系（-）Sca-1（+）CD 117（+）（LSK）细胞的联合作用，研究了造血生态位元素对HSC和HPC功能的影响。与SC培养物相比，在OB中培养的谱系（-）Sca-1（+）CD 117（+）细胞的CFU扩增和骨髓重建潜力显著更高，从而证实了OB在造血生态位能力中的重要性。OB介导的HSC和HPC功能的增强在OB和SC的共培养物中减少，表明SC抑制OB介导的造血增强活性。虽然SC的抑制作用是由脂肪细胞介导的，可能是通过上调神经纤毛蛋白-1，OB介导的增强造血功能是通过Notch信号。Notch 2、Jagged 1和2、Delta 1和4、Hes 1和5以及Deltex的表达在OB培养物中增加，而在SC和OB/SC培养物中受到抑制。OBs的表型分馏没有分离造血增强活性，但表明这种功能是共同的OBs从不同的解剖部位。这些数据说明OB促进造血功能的体外维持，包括通过上调HSC和OB之间的Notch介导的信号传导而重新增殖的潜力。2010; 115（16）：3239-3248）
Hematopoietic stem (HSC) and progenitor (HPC) cell fate is governed by intrinsic and extrinsic parameters. We examined the impact of hematopoietic niche elements on HSC and HPC function by analyzing the combined effect of osteoblasts (OBs) and stromal cells (SCs) on Lineage(-)Sca-1(+)CD117(+) (LSK) cells. CFU expansion and marrow repopulating potential of cultured Lineage(-)Sca-1(+)CD117(+) cells were significantly higher in OB compared with SC cultures, thus corroborating the importance of OBs in the competence of the hematopoietic niche. OB-mediated enhancement of HSC and HPC function was reduced in cocultures of OBs and SCs, suggesting that SCs suppressed the OB-mediated hematopoiesis-enhancing activity. Although the suppressive effect of SC was mediated by adipocytes, probably through up-regulation of neuropilin-1, the OB-mediated enhanced hematopoiesis function was elaborated through Notch signaling. Expression of Notch 2, Jagged 1 and 2, Delta 1 and 4, Hes 1 and 5, and Deltex was increased in OB cultures and suppressed in SC and OB/SC cultures. Phenotypic fractionation of OBs did not segregate the hematopoiesis-enhancing activity but demonstrated that this function is common to OBs from different anatomic sites. These data illustrate that OBs promote in vitro maintenance of hematopoietic functions, including repopulating potential by up-regulating Notch-mediated signaling between HSCs and OBs. (Blood. 2010; 115(16): 3239-3248)