Hematopoietic stem cell maintenance by Mediator transcriptional coregulator complex

在缺乏MED 1亚基的介体转录辅助调节因子复合物的小鼠胚胎成纤维细胞（MEFs）中，FGF 7的表达减弱。当正常小鼠骨髓（BM）细胞与BM基质细胞在抗FGF 7抗体存在下共培养时，BM细胞的生长和长时间培养起始细胞（LTC-ICs）的数量显著减少。抗FGF 7抗体还减弱了MB 1基质细胞依赖性成髓细胞瘤细胞的增殖和鹅卵石形成。向BM细胞和Med 1-/- MEFs的共培养物中添加重组FGF 7增加了BM细胞和LTC-IC。FGF 7及其同源受体FGFR 2 IIIb在BM细胞中检测不到，但MEFs和BM基质细胞表达两者。FGF 7激活野生型MEF、MED 1敲除MEF和BM基质细胞中FGFR 2 IIIb的下游靶标。总而言之，我们认为FGF 7通过基质细胞上表达的FGFR 2 IIIb间接支持HSPC和白血病起始细胞。

FGF7 expression was attenuated in mouse embryonic fibroblasts (MEFs) deficient for the MED1 subunit of the Mediator transcriptional coregulator complex. When normal mouse bone marrow (BM) cells were cocultured with BM stromal cells in the presence of anti-FGF7 antibody, the growth of BM cells and the number of long-time culture-initiating cells (LTC-ICs) decreased significantly. Anti-FGF7 antibody also attenuated the proliferation and cobblestone formation of MB1 stromal cell-dependent myeloblastoma cells. The addition of recombinant FGF7 to the coculture of BM cells and Med1-/- MEFs increased BM cells and LTC-ICs. FGF7 and its cognate receptor, FGFR2IIIb, were undetectable in BM cells, but MEFs and BM stromal cells expressed both. FGF7 activated downstream targets of FGFR2IIIb in wild type MEFs, MED1 knockout MEFs, and BM stromal cells. Taken together, we propose that FGF7 supports HSPCs and leukemia-initiating cells indirectly via FGFR2IIIb expressed on stromal cells.