Division of Cellular Immunology, German Cancer Research Center, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany.
Division of Cellular Immunology, German Cancer Research Center, 69120 Heidelberg, Germany; Faculty of Medicine, Heidelberg University, 69120 Heidelberg, Germany.
Cell Stem Cell. 2023 Feb 2;30(2):207-218.e7. doi: 10.1016/j.stem.2022.12.014. Epub 2023 Jan 17.
In response to infections and stress, hematopoiesis rapidly enhances blood and immune cell production. The stage within the hematopoietic hierarchy that accounts for this regeneration is unclear under natural conditions in vivo. We analyzed by differentiation tracing, using inducible Tie2- or Flt3-driven Cre recombinase, the roles of mouse hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs). During polymicrobial sepsis, HSCs responded transcriptionally and increased their proliferation and cell death, yet HSC differentiation rates remained at steady-state levels. HSC differentiation was also independent from the ablation of various cellular compartments-bleeding, the antibody-mediated ablation of granulocytes or B lymphocytes, and genetic lymphocyte deficiency. By marked contrast, the fate mapping of MPPs in polymicrobial sepsis identified these cells as a major source for accelerated myeloid cell production. The regulation of blood and immune cell homeostasis by progenitors rather than stem cells may ensure a rapid response while preserving the integrity of the HSC population.
针对感染和应激，造血系统会迅速增强血液和免疫细胞的生成。在体内自然条件下，尚不清楚造血系统层级中负责这种再生的阶段。我们通过分化追踪进行了分析，使用诱导型 Tie2 或 Flt3 驱动的 Cre 重组酶，研究了小鼠造血干细胞（HSC）和多能祖细胞（MPP）的作用。在多微生物脓毒症中，HSC 在转录水平上做出响应，增加了其增殖和细胞死亡，但 HSC 分化率仍保持在稳定水平。HSC 的分化也不依赖于各种细胞区室的消融 - 出血、抗粒细胞或 B 淋巴细胞的抗体消融，以及遗传的淋巴细胞缺失。相比之下，在多微生物脓毒症中对 MPP 的命运图谱分析将这些细胞确定为加速髓样细胞生成的主要来源。祖细胞而不是干细胞对血液和免疫细胞动态平衡的调节可能确保了快速反应，同时保持了 HSC 群体的完整性。
