Characterization and exploration of bone marrow niche regulators for hematopoietic stem cells

为了了解造血干细胞(HSC)与骨髓细胞的相互作用，我们研究了趋化因子CXCL14和纤毛蛋白CMG-1的功能，并寻找HSC作用转录因子LHX2的下游效应分子。我们发现CXCL14以高亲和力与CXCR4结合，并完全抑制CXCL12介导的造血祖细胞的迁移。然而，CXCL14基因敲除小鼠的骨髓HSCs数量和频率与野生型小鼠相似。在HSC特异性CMG-1条件性基因敲除小鼠的骨髓中也是如此。最后，我们通过LHX2触发的ES细胞扩增培养寻找与HSCs未分化状态相关的膜蛋白。结果，我们确定了几个候选基因，如Biglycan、Esam1和Jam3。

To understand how hematopoietic stem cells (HSCs) interact with bone marrow niche, we investigated functions of chemokine CXCL14 and cilia protein CMG-1, and searched for downstream effector molecules of the HSC-acting transcription factor Lhx2. We discovered that CXCL14 binds to CXCR4 with high affinity and completely inhibits the CXCL12-mediated migration of hematopoietic progenitor cells. However, number and frequency of bone marrow HSCs in CXCL14 knockout mice were similar as those in wild type mice. Same thing was true in bone marrows of HSC-specific CMG-1 conditional knockout mice. Lastly, we searched for membrane proteins that are relevant to the undifferentiated status of HSCs by using an Lhx2-trigerred HSC expansion culture of ES cells. As a result, we identified several candidate genes such as Biglycan, Esam1, and Jam3.