Studies over the last couple of decades have shown that hematopoietic stem cells (HSCs) are critically dependent on cytokines such as Stem Cell Factor and other signals provided by bone marrow niches comprising of mesenchymal stem and progenitor cells (MSPCs) and endothelial cells (ECs). Because of their critical roles in HSC maintenance the niches formed by MSPCs and ECs are commonly referred to as HSC niches. For the most part, the signals required for HSC maintenance act in a short-range manner, which imposes the necessity for directional and positional cues in order for HSCs to localize and be retained properly in stem cell niches. The chemokine CXCL12 and its Gαi protein coupled receptor CXCR4, besides promoting HSC quiescence directly, also play instrumental roles in enabling HSCs to access bone marrow stem cell niches. Recent studies have revealed, however, that HSC niches also provide a constellation of hematopoietic cytokines that are critical for the production of most, if not all, blood cell types. Some hematopoietic cytokines, namely IL-7 and IL-15 produced by HSC niches, are not only required for lymphopoiesis but are also essential for memory T cell maintenance. Consequently, hematopoietic progenitors and differentiated immune cells, such as memory T cell subsets, also depend on the CXCL12/CXCR4 axis for migration into bone marrow and interactions with MSPCs and ECs. Similarly, subsets of antibody-secreting plasma cells also reside in close association with CXCL12-producing MSPCs in the bone marrow and require the CXCR4/CXCL12 axis for survival and long-term maintenance. Collectively, these studies demonstrate a broad range of key physiological roles, spanning blood cell production and maintenance of immunological memory, that are orchestrated by stem cell niches through a common and simple mechanism: CXCL12/CXCR4-mediated cell recruitment followed by receipt of a maintenance and/or instructive signal. A fundamental flaw of this type of cellular organization is revealed by myeloid and lymphoid leukemias, which target stem cell niches and induce profound transcriptomic changes that result in reduced hematopoietic activity and altered mesenchymal cell differentiation.

过去几十年的研究表明，造血干细胞 (HSC) 严重依赖细胞因子，如干细胞因子和骨髓壁龛提供的其他信号，包括间充质干细胞和祖细胞 (MSPC) 和内皮细胞 (EC) . 由于它们在 HSC 维护中的关键作用，由 MSPC 和 EC 形成的壁龛通常被称为 HSC 壁龛。在大多数情况下，HSC 维持所需的信号以短程方式起作用，这就需要定向和位置提示，以便 HSC 定位并正确保留在干细胞壁龛中。趋化因子 CXCL12 及其 Gαi 蛋白偶联受体 CXCR4 除了直接促进 HSC 静止外，还在使 HSC 进入骨髓干细胞壁龛方面发挥重要作用。然而，最近的研究表明，HSC 壁龛还提供了一组造血细胞因子，这些细胞因子对于大多数（如果不是全部）血细胞类型的产生至关重要。一些造血细胞因子，即由 HSC 壁龛产生的 IL-7 和 IL-15，不仅是淋巴细胞生成所必需的，而且对于记忆 T 细胞的维持也是必不可少的。因此，造血祖细胞和分化的免疫细胞，如记忆 T 细胞亚群，也依赖于 CXCL12/CXCR4 轴迁移到骨髓以及与 MSPC 和 EC 相互作用。同样，分泌抗体的浆细胞亚群也与骨髓中产生 CXCL12 的 MSPC 密切相关，并且需要 CXCR4/CXCL12 轴才能存活和长期维持。总的来说，这些研究证明了广泛的关键生理作用，跨越血细胞产生和免疫记忆的维持，由干细胞壁龛通过一种常见且简单的机制进行协调：CXCL12/CXCR4 介导的细胞募集，然后接收维持和/或指导性信号。髓系和淋巴系白血病揭示了这种细胞组织的基本缺陷，它们靶向干细胞壁龛并诱导深刻的转录组变化，导致造血活性降低和间充质细胞分化改变。