Department of Biochemistry and Molecular Biology, University of Salamanca, Salamanca 37007, Spain; IBSAL (Instituto de Investigación Biomédica de Salamanca), Salamanca 37007, Spain.
IBSAL (Instituto de Investigación Biomédica de Salamanca), Salamanca 37007, Spain.
Stem Cell Reports. 2015 Oct 13;5(4):516-31. doi: 10.1016/j.stemcr.2015.08.003. Epub 2015 Sep 3.
The regulation of hematopoietic stem cells (HSCs) depends on the integration of the multiple signals received from the bone marrow niche. We show the relevance of the protein tyrosine phosphatase PTPN13 and β-catenin as intracellular signaling molecules to control HSCs adhesiveness, cell cycling, and quiescence. Lethally irradiated mice transplanted with Lin(-) bone marrow cells in which PTPN13 or β-catenin had been silenced showed a significant increase of long-term (LT) and short-term (ST) HSCs. A decrease in cycling cells was also found, together with an increase in quiescence. The decreased expression of PTPN13 or β-catenin was linked to the upregulation of several genes coding for integrins and several cadherins, explaining the higher cell adhesiveness. Our data are consistent with the notion that the levels of PTPN13 and β-catenin must be strictly regulated by extracellular signaling to regulate HSC attachment to the niche and the balance between proliferation and quiescence.
造血干细胞（HSCs）的调节取决于其从骨髓龛中接收的多种信号的整合。我们展示了蛋白酪氨酸磷酸酶 PTPN13 和 β-连环蛋白作为细胞内信号分子的相关性，以控制 HSCs 的黏附性、细胞周期和静止状态。用沉默了 PTPN13 或 β-连环蛋白的 Lin(-)骨髓细胞进行致死性辐照的小鼠移植后，长期（LT）和短期（ST）HSCs 显著增加。还发现循环细胞减少，静止细胞增加。PTPN13 或 β-连环蛋白表达降低与编码整合素和几种钙黏蛋白的几个基因的上调有关，这解释了更高的细胞黏附性。我们的数据与以下观点一致，即 PTPN13 和 β-连环蛋白的水平必须通过细胞外信号严格调节，以调节 HSC 与龛的附着以及增殖和静止之间的平衡。
