Division of Stem Cell Therapy, Center for Stem Cell Biology and Regeneration Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Division of Stem Cell Therapy, Center for Stem Cell Biology and Regeneration Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena 07745, Germany.
Cell. 2013 Aug 29;154(5):1112-1126. doi: 10.1016/j.cell.2013.08.007.
Consensus holds that hematopoietic stem cells (HSCs) give rise to multipotent progenitors (MPPs) of reduced self-renewal potential and that MPPs eventually produce lineage-committed progenitor cells in a stepwise manner. Using a single-cell transplantation system and marker mice, we unexpectedly found myeloid-restricted progenitors with long-term repopulating activity (MyRPs), which are lineage-committed to megakaryocytes, megakaryocyte-erythroid cells, or common myeloid cells (MkRPs, MERPs, or CMRPs, respectively) in the phenotypically defined HSC compartment together with HSCs. Paired daughter cell assays combined with transplantation revealed that HSCs can give rise to HSCs via symmetric division or directly differentiate into MyRPs via asymmetric division (yielding HSC-MkRP or HSC-CMRP pairs). These myeloid bypass pathways could be essential for fast responses to ablation stress. Our results show that loss of self-renewal and stepwise progression through specific differentiation stages are not essential for lineage commitment of HSCs and suggest a revised model of hematopoietic differentiation.
普遍认为，造血干细胞 (HSCs) 产生自我更新能力降低的多能祖细胞 (MPPs)，而 MPPs 最终以逐步的方式产生谱系定向祖细胞。使用单细胞移植系统和标记小鼠，我们出人意料地发现了具有长期重编程活性的髓系限制祖细胞（MyRPs），它们在表型定义的 HSC 区室中与 HSCs 一起，分别向巨核细胞、巨核细胞-红细胞细胞或共同髓系细胞（MkRPs、MERP 或 CMRPs）谱系定向。配对子细胞测定结合移植表明，HSCs 可以通过对称分裂产生 HSCs，或者通过不对称分裂直接分化为 MyRPs（产生 HSC-MkRP 或 HSC-CMRP 对）。这些髓系旁路途径可能对快速应对消融应激至关重要。我们的研究结果表明，自我更新的丧失和通过特定分化阶段的逐步进展对于 HSCs 的谱系决定不是必需的，并提出了一个修正的造血分化模型。
