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

为了了解造血干细胞（HSC）如何与骨髓小生境相互作用，我们研究了趋化因子CXCL 14和纤毛蛋白CMG-1的功能，并寻找HSC作用转录因子Lhx 2的下游效应分子。我们发现CXCL 14以高亲和力结合CXCR 4并完全抑制CXCL 12介导的造血祖细胞迁移。然而，CXCL 14基因敲除小鼠骨髓造血干细胞的数量和频率与野生型小鼠相似。在HSC特异性CMG-1条件性敲除小鼠的骨髓中也是如此。最后，我们通过使用ES细胞的Lhx 2-trigerred HSC扩增培养物来寻找与HSC未分化状态相关的膜蛋白。因此，我们确定了几个候选基因，如Biglycan，Esam 1和Jam 3。

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.