Yang Dan, Zhang Xiangzhong, Dong Yong, Liu Xiaofei, Wang Tongjie, Wang Xiaoshan, Geng Yang, Fang Shumin, Zheng Yi, Chen Xiaoli, Chen Jiekai, Pan Guangjin, Wang Jinyong
a Department of Hematology ; Third Affiliated Hospital of Sun Yat-Sen University ; Guangzhou , China.
Cell Cycle. 2015;14(4):612-20. doi: 10.4161/15384101.2014.992191.
Hoxa5 is preferentially expressed in haematopoietic stem cells (HSCs) and multipotent progenitor cells (MPPs), and is more highly expressed in expanding HSCs. To date, little is known regarding the role of Hoxa5 in HSCs and downstream progenitor cells in vivo. In this study, we show that increased expression of Hoxa5 in haematopoietic stem cells leads to aberrant erythropoiesis in vivo. Hoxa5 differentially modifies the cell cycle of HSCs and lineage committed progenitor cells, depending on the cellular context. Hoxa5 drives HSCs, but not MPPs, through the cell cycle and arrests erythroid progenitor cells in G0 phase. Although the HSC pool shrinks after overexpression of Hoxa5, HSCs sustain the abilities of self-renewal and multipotency. In vivo, Hoxa5 has two effects on erythropoiesis: it causes a predominance of mature erythroid lineage cells and the partial apoptosis of erythroid progenitors. RNA-seq indicates that multiple biological processes, including erythrocyte homeostasis, cell metabolism, and apoptosis, are modified by Hoxa5. The results of this study indicate that Hoxa5 is a key regulator of the HSC cell cycle, and the inappropriate expression of Hoxa5 in lineage-committed progenitor cells leads to aberrant erythropoiesis.
Hoxa5在造血干细胞（HSC）和多能祖细胞（MPP）中优先表达，并且在增殖的造血干细胞中表达更高。迄今为止，关于Hoxa5在体内造血干细胞和下游祖细胞中的作用知之甚少。在本研究中，我们表明造血干细胞中Hoxa5表达增加会导致体内异常红细胞生成。根据细胞环境，Hoxa5对造血干细胞和定向祖细胞的细胞周期有不同的调节作用。Hoxa5驱动造血干细胞而非多能祖细胞通过细胞周期，并使红系祖细胞停滞在G0期。虽然Hoxa5过表达后造血干细胞池缩小，但造血干细胞仍维持自我更新和多能性的能力。在体内，Hoxa5对红细胞生成有两种作用：它导致成熟红系谱系细胞占优势以及红系祖细胞部分凋亡。RNA测序表明，包括红细胞稳态、细胞代谢和凋亡在内的多个生物学过程受到Hoxa5的影响。本研究结果表明，Hoxa5是造血干细胞细胞周期的关键调节因子，并且Hoxa5在定向祖细胞中的不适当表达会导致异常红细胞生成。
