Liu Fangshu, Sun Xiaofan, Deng Suqi, Wu Yingying, Liu Xingcheng, Wu Caiping, Huang Kexiu, Li Yue, Dong Zexuan, Xiao Weihao, Li Manchun, Chen Zhiyang, Ju Zhenyu, Xiao Jia, Du Juan, Zeng Hui
Department of Hematology, The First Affiliated Hospital of Jinan University, 613W Huangpu Rd, Guangzhou, Guangdong, 510632, China.
Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, 510632, China.
Stem Cell Res Ther. 2024 Aug 7;15(1):248. doi: 10.1186/s13287-024-03861-7.
The function of hematopoietic stem cells (HSC) is regulated by HSC internal signaling pathways and their microenvironment. Chemokines and chemokine ligands play important roles in the regulation of HSC function. Yet, their functions in HSC are not fully understood.
We established Cxcr3 and Cxcl10 knockout mouse models (Cxcr3 and Cxcl10) to analyze the roles of Cxcr3 or Cxcl10 in regulating HSC function. The cell cycle distribution of LT-HSC was assessed via flow cytometry. Cxcr3 and Cxcl10stem/progenitor cells showed reduced self-renewal capacity as measured in serial transplantation assays. To study the effects of Cxcr3 or Cxcl10 deficient bone marrow microenvironment, we transplanted CD45.1 donor cells into Cxcr3or Cxcl10 recipient mice (CD45.2) and examined donor-contributed hematopoiesis.
Deficiency of Cxcl10 and its receptor Cxcr3 led to decreased BM cellularity in mice, with a significantly increased proportion of LT-HSC. Cxcl10 stem/progenitor cells showed reduced self-renewal capacity in the secondary transplantation assay. Notably, Cxcl10 donor-derived cells preferentially differentiated into B lymphocytes, with skewed myeloid differentiation ability. Meanwhile, Cxcr3-deficient HSCs demonstrated a reconstitution disadvantage in secondary transplantation, but the lineage bias was not significant. Interestingly, the absence of Cxcl10 or Cxcr3 in bone marrow microenvironment did not affect HSC function.
The Cxcl10 and Cxcr3 regulate the function of HSC, including self-renewal and differentiation, adding to the understanding of the roles of chemokines in the regulation of HSC function.
造血干细胞（HSC）的功能受HSC内部信号通路及其微环境的调节。趋化因子和趋化因子配体在HSC功能调节中发挥重要作用。然而，它们在HSC中的功能尚未完全明确。
我们建立了Cxcr3和Cxcl10基因敲除小鼠模型（Cxcr3 -/-和Cxcl10 -/-），以分析Cxcr3或Cxcl10在调节HSC功能中的作用。通过流式细胞术评估长期造血干细胞（LT - HSC）的细胞周期分布。在连续移植试验中，Cxcr3 -/-和Cxcl10 -/-干/祖细胞显示出自我更新能力降低。为了研究Cxcr3或Cxcl10缺陷的骨髓微环境的影响，我们将CD45.1供体细胞移植到Cxcr3 -/-或Cxcl10 -/-受体小鼠（CD45.2）中，并检查供体来源的造血情况。
Cxcl10及其受体Cxcr3的缺陷导致小鼠骨髓细胞数量减少，LT - HSC的比例显著增加。在二次移植试验中，Cxcl10 -/-干/祖细胞显示出自我更新能力降低。值得注意的是，Cxcl10供体来源的细胞优先分化为B淋巴细胞，髓系分化能力偏向。同时，Cxcr3缺陷的造血干细胞在二次移植中表现出重建劣势，但谱系偏向不显著。有趣的是，骨髓微环境中Cxcl10或Cxcr3的缺失并不影响造血干细胞的功能。
Cxcl10和Cxcr3调节造血干细胞的功能，包括自我更新和分化，这有助于加深对趋化因子在造血干细胞功能调节中作用的理解。
