Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden.
Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden; Stem Cell Group, Cancer Institute, University College London, London, UK.
Stem Cell Reports. 2023 Mar 14;18(3):736-748. doi: 10.1016/j.stemcr.2023.01.014. Epub 2023 Mar 2.
Mouse hematopoietic stem cells (HSCs) have been extensively defined both molecularly and functionally at steady state, while regenerative stress induces immunophenotypical changes that limit high purity isolation and analysis. It is therefore important to identify markers that specifically label activated HSCs to gain further knowledge about their molecular and functional properties. Here, we assessed the expression of macrophage-1 antigen (MAC-1) on HSCs during regeneration following transplantation and observed a transient increase in MAC-1 expression during the early reconstitution phase. Serial transplantation experiments demonstrated that reconstitution potential was highly enriched in the MAC-1 portion of the HSC pool. Moreover, in contrast to previous reports, we found that MAC-1 expression inversely correlates with cell cycling, and global transcriptome analysis showed that regenerating MAC-1 HSCs share molecular features with stem cells with low mitotic history. Taken together, our results suggest that MAC-1 expression marks predominantly quiescent and functionally superior HSCs during early regeneration.
小鼠造血干细胞（HSCs）在稳态时已经在分子和功能上得到了广泛的定义，而再生应激会诱导免疫表型变化，限制了高纯度的分离和分析。因此，确定能够特异性标记激活 HSCs 的标志物对于进一步了解它们的分子和功能特性非常重要。在这里，我们在移植后的再生过程中评估了巨噬细胞-1 抗原（MAC-1）在 HSCs 上的表达情况，并观察到在早期重建阶段 MAC-1 表达短暂增加。连续移植实验表明，重建潜能在 HSC 池的 MAC-1 部分高度富集。此外，与之前的报告相反，我们发现 MAC-1 表达与细胞周期呈负相关，并且全转录组分析表明，再生的 MAC-1 HSCs 具有与具有低有丝分裂历史的干细胞相似的分子特征。总之，我们的研究结果表明，在早期再生过程中，MAC-1 表达主要标记静止和功能优越的 HSCs。
