CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
University of Chinese Academy of Sciences, Beijing, China.
Cell Prolif. 2022 Jun;55(6):e13235. doi: 10.1111/cpr.13235. Epub 2022 May 17.
The expression of transcription factor Hoxb5 specifically marks the functional haematopoietic stem cells (HSC) in mice. However, our recent work demonstrated that ectopic expression of Hoxb5 exerted little effect on HSC but could convert B-cell progenitors into functional T cells in vivo. Thus, cell type- and development stage-specific roles of Hoxb5 in haematopoietic hierarchy await more extensive exploration. In this study, we aim to investigate the effect of Hoxb5 expression in multipotent blood progenitor cells.
A Mx1cre/Rosa mouse model was used to evaluate the effect of Hoxb5 expression in blood multipotent progenitor cells (MPP). Golden standard serial transplantation experiments were used to test the long-term haematopoiesis potential of Hoxb5-expressing MPP. Single-cell RNA-seq analysis was used to characterize the gained molecular features of Hoxb5-expressing MPP and to compare with the global transcriptome features of natural adult HSC and fetal liver HSC (FL HSC).
Here, with a mouse strain engineered with conditional expression of Hoxb5, we unveiled that induced expression of Hoxb5 in MPP led to the generation of a de novo Sca1 c-kit CD11b CD48 (CD11b CD48 SK) cell type, which can repopulate long-term multilineage haematopoiesis in serial transplantations. RNA-seq analysis showed that CD11b CD48 SK cells exhibited acquired features of DNA replication and cell division.
Our current study uncovers that Hoxb5 can empower MPP with self-renewal ability and indicates an alternative approach for generating HSC-like cells in vivo from blood lineage cells.
转录因子 Hoxb5 的表达特异性标记了小鼠中的功能性造血干细胞（HSC）。然而，我们最近的工作表明，Hoxb5 的异位表达对 HSC 几乎没有影响，但可以在体内将 B 细胞前体细胞转化为功能性 T 细胞。因此，Hoxb5 在造血层级结构中的细胞类型和发育阶段特异性作用需要更广泛的探索。在本研究中，我们旨在研究 Hoxb5 表达在多潜能血液祖细胞中的作用。
使用 Mx1cre/Rosa 小鼠模型来评估 Hoxb5 在血液多潜能祖细胞（MPP）中的表达效果。使用黄金标准系列移植实验来测试 Hoxb5 表达的 MPP 的长期造血潜能。单细胞 RNA-seq 分析用于表征 Hoxb5 表达的 MPP 获得的分子特征，并与天然成体 HSC 和胎肝 HSC（FL HSC）的全基因组转录组特征进行比较。
在这里，我们使用一种工程化的条件性表达 Hoxb5 的小鼠品系，揭示了在 MPP 中诱导表达 Hoxb5 会导致产生一种新的 Sca1 c-kit CD11b CD48（CD11b CD48 SK）细胞类型，该细胞类型可以在系列移植中重新生成长期多谱系造血。RNA-seq 分析表明，CD11b CD48 SK 细胞表现出获得的 DNA 复制和细胞分裂特征。
我们目前的研究揭示了 Hoxb5 可以赋予 MPP 自我更新能力，并表明了一种从血液谱系细胞体内生成 HSC 样细胞的替代方法。
