Lim Hong Kiat, Periasamy Pravin, O'Neill Helen C
Clem Jones Research Centre for Regenerative Medicine, Bond University, Gold Coast, Australia.
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Stem Cells Int. 2018 Dec 25;2018:9896142. doi: 10.1155/2018/9896142. eCollection 2018.
There are very few model systems which demonstrate hematopoiesis . Previously, we described unique splenic stromal cell lines which support the development of hematopoietic cells and particularly myeloid cells. Here, the 5G3 spleen stromal cell line has been investigated for capacity to support the differentiation of hematopoietic cells from progenitors . Initially, 5G3 was shown to express markers of mesenchymal but not endothelial or hematopoietic cells and to resemble perivascular reticular cells in the bone marrow through gene expression. In particular, 5G3 resembles CXCL12-abundant reticular cells or perivascular reticular cells, which are important niche elements for hematopoiesis in the bone marrow. To analyse the hematopoietic support function of 5G3, specific signaling pathway inhibitors were tested for the ability to regulate cell production in cocultures of stroma overlaid with bone marrow-derived hematopoietic stem/progenitor cells. These studies identified an important role for Wnt and Notch pathways as well as tyrosine kinase receptors like c-KIT and PDGFR. Cell production in stromal cocultures constitutes hematopoiesis, since signaling pathways provided by splenic stroma reflect those which support hematopoiesis in the bone marrow.
很少有模型系统能展示造血过程。此前，我们描述了独特的脾基质细胞系，其能支持造血细胞尤其是髓系细胞的发育。在此，我们对5G3脾基质细胞系支持造血祖细胞分化为造血细胞的能力进行了研究。最初，5G3被证明表达间充质细胞标志物，而不表达内皮细胞或造血细胞标志物，并且通过基因表达显示其类似于骨髓中的血管周围网状细胞。特别是，5G3类似于CXCL12丰富的网状细胞或血管周围网状细胞，它们是骨髓中造血的重要微环境成分。为了分析5G3的造血支持功能，我们测试了特定信号通路抑制剂调节覆盖有骨髓来源的造血干/祖细胞的基质共培养物中细胞生成的能力。这些研究确定了Wnt和Notch信号通路以及c-KIT和PDGFR等酪氨酸激酶受体的重要作用。基质共培养物中的细胞生成构成了造血过程，因为脾基质提供的信号通路反映了那些支持骨髓造血的信号通路。
