Differentially regulated genes in normal LT-HSC vs ST-HSC. Mus musculus

Self-renewal is a defining characteristic of stem cells, however the molecular pathways underlying its regulation are poorly understood. Here we demonstrate that conditional inactivation of the Pbx1 proto-oncogene in the hematopoietic compartment results in a progressive loss of long-term hematopoietic stem cells (LT-HSCs) that is associated with concomitant reduction in their quiescence, leading to a defect in the maintenance of self-renewal as assessed by serial transplantation. Transcriptional profiling revealed that multiple stem cell maintenance factors are perturbed in Pbx1-deficient LT-HSCs, which prematurely express a large subset of genes, including cell cycle regulators, normally expressed in non-self-renewing multipotent progenitors. Keywords: cell type comparison Overall design: LT-HSC (Lin-cKit+Sca1+CD34-CD135-) and ST-HSC (Lin-cKit+Sca1+CD34+CD135-) cells were prospectively sorted from the BM of MxCre-.Pbx1f/f control mice harvested 4 weeks after the last injection of poly(I:C).

自我更新是干细胞的标志性特征之一，但其调控的分子通路目前仍未得到充分阐明。本研究证实，在造血区室中对原癌基因Pbx1实施条件性失活，可导致长期造血干细胞（long-term hematopoietic stem cells, LT-HSCs）进行性丢失，同时伴随其静止态水平下降，最终引发通过连续移植实验评估的自我更新维持缺陷。转录谱分析显示，在Pbx1缺陷的LT-HSCs中，多种干细胞维持因子的表达出现紊乱；这些细胞会提前表达大量本应在非自我更新型多能祖细胞中表达的基因，其中包括细胞周期调控因子。关键词：细胞类型比较
实验设计：在末次聚肌胞苷酸（poly(I:C)）注射4周后，从MxCre⁻.Pbx1f/f对照小鼠的骨髓（BM）中前瞻性分选出长期造血干细胞（LT-HSC，Lin⁻cKit⁺Sca1⁺CD34⁻CD135⁻）与短期造血干细胞（ST-HSC，Lin⁻cKit⁺Sca1⁺CD34⁺CD135⁺）细胞。