Hoxb5 reprogrammes murine multipotent blood progenitors into haematopoietic stem cell-like cells.
Hoxb5 reprogrammes murine multipotent blood progenitors into haematopoietic stem cell-like cells.
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Hoxb5 将小鼠多能血液祖细胞重编程为造血干细胞样细胞
DOI：
10.1111/cpr.13235
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发表时间：
2022-06
影响因子：
8.5
通讯作者：
中科院分区：
文献类型：
--
作者：
转录因子Hoxb 5的表达特异性地标记小鼠造血干细胞（HSC）的功能。然而，我们最近的工作表明Hoxb 5的异位表达对HSC几乎没有影响，但可以在体内将B-祖细胞转化为功能性T细胞。因此，Hoxb 5在造血层次中的细胞类型和发育阶段特异性作用有待更广泛的探索。在这项研究中，我们的目的是研究Hoxb 5表达在多能造血祖细胞中的作用。使用Mxlcre/RosaLSL-Hoxb 5-EGFP/+小鼠模型来评估血液多能祖细胞（MPP）中Hoxb 5表达的效果。金标准系列移植实验用于测试表达Hoxb 5的MPP的长期造血潜能。使用单细胞RNA-seq分析来表征所获得的表达Hoxb 5的MPP的分子特征，并与天然成体HSC和胎肝HSC（FL HSC）的总体转录组特征进行比较。在这里，我们用Hoxb 5条件性表达的小鼠品系，揭示了MPP中Hoxb 5的诱导表达导致从头Sca 1 + c-kit + CD 11b + CD 48+（CD 11b + CD 48 +SK）细胞类型的产生，其可以在连续移植中重新填充长期多系造血。RNA-seq分析显示CD 11b + CD 48 +SK细胞表现出DNA复制和细胞分裂的获得性特征。我们目前的研究揭示了Hoxb 5可以使MPP具有自我更新能力，并指出了一种从血液谱系细胞体内产生HSC样细胞的替代方法。我们揭示了Hoxb 5在小鼠多能祖细胞（MPP）中的诱导表达导致从头Sca 1 +c‐Kit+ CD 11b + CD 48+（CD 11b + CD 48 +SK）细胞类型的产生，该细胞类型获得了自我更新能力，并且可以在连续移植受者中重建长期多系造血。RNA序列分析显示，CD 11b + CD 48 +SK细胞表现出获得性的DNA复制和细胞分裂特征，类似于天然FL HSC。简而言之，我们目前的研究揭示了Hoxb 5能够赋予MPP自我更新能力，并指出了一种从血液谱系细胞体内产生HSC样细胞的替代方法。
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/RosaLSL‐Hoxb5‐EGFP/+ 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. We unveiled that induced expression of Hoxb5 in mouse multipotent progenitor cells (MPP) led to the generation of a de novo Sca1+c‐Kit+CD11b+CD48+ (CD11b+CD48+SK) cell type, which obtained the self‐renewal ability and can repopulate long‐term multilineage haematopoiesis in serial transplant recipients. RNA‐seq analysis showed that CD11b+CD48+SK cells exhibited acquired features of DNA replication and cell division, which resembled natural FL HSC. In short, our current study uncovers that Hoxb5 is able to empower MPPs with self‐renewal ability and indicates an alternative approach for generating HSC‐like cells in vivo from blood lineage cells.
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影响因子：
64.5
作者：
Bernitz, Jeffrey M.;Kim, Huen Suk;MacArthur, Ben;Sieburg, Hans;Moore, Kateri
通讯作者：
Moore, Kateri
影响因子：
64.8
作者：
Chen JY;Miyanishi M;Wang SK;Yamazaki S;Sinha R;Kao KS;Seita J;Sahoo D;Nakauchi H;Weissman IL
通讯作者：
Weissman IL
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
DOI：
10.1073/pnas.1315464111
发表时间：
2014-02-25
影响因子：
11.1
作者：
Baker, Stacey J.;Ma'ayan, Avi;Reddy, E. Premkumar
通讯作者：
Reddy, E. Premkumar
DOI：
10.1073/pnas.0500303102
发表时间：
2005-08-09
影响因子：
11.1
作者：
Gurbuxani, S;Xu, YF;Crispino, JD
通讯作者：
Crispino, JD