Vascular Notch Signaling in Stress Hematopoiesis.
Vascular Notch Signaling in Stress Hematopoiesis.
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应激造血中的血管缺口信号。
DOI：
10.3389/fcell.2020.606448
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发表时间：
2020
影响因子：
5.5
通讯作者：
Guo P
中科院分区：
文献类型：
--
作者：
Huang C;Yang D;Ye GW;Powell CA;Guo P
规范Notch信号是最保守的信号级联之一。它在发育和癌症期间调节多种生物系统中的细胞增殖、细胞分化和细胞命运维持（Fortini、Kopan 和 Ilagan、Andersson 等人、Ntziachristos 等人）。对于造血系统，在胚胎发育过程中，Notch1 对于背主动脉主动脉-前角-中肾区域造血干细胞 (HSC) 的出现至关重要。在成年阶段，Notch 受体和 Notch 靶标在不同的造血细胞类型中以不同水平表达，并影响谱系选择。例如，Notch 指定 T 细胞谱系高于 B 细胞。然而，对于成人 HSC 的维持是否需要 Notch 信号传导，一直存在长期争论，利用转基因动物灭活 HSC 或微环境细胞中 Notch 信号传导途径的不同成分。当前小型审查的目的是总结反对或支持此类假设的证据，并指出有待解决的迫切问题；因此，一些看似矛盾的发现可以得到调和。我们需要使用生化检测更好地描述 Notch 信号传导事件，以识别特定生物背景下 HSC 或利基细胞内的直接 Notch 靶标。更重要的是，我们呼吁进行更详细的研究，研究利基细胞类型（血管内皮细胞或其他基质细胞）特异性Notch配体是否在T淋巴细胞淋巴瘤（T-ALL）或慢性粒单核细胞白血病（CMML）的进展过程中调节实体瘤中T细胞的分化。我们相信，研究血管内皮细胞或其他基质细胞类型在稳态和应激期间与造血细胞的相互作用可以为特定且有效的Notch相关治疗提供见解。
Canonical Notch signaling is one of the most conserved signaling cascades. It regulates cell proliferation, cell differentiation, and cell fate maintenance in a variety of biological systems during development and cancer (Fortini,; Kopan and Ilagan,; Andersson et al.,; Ntziachristos et al.,). For the hematopoietic system, during embryonic development, Notch1 is essential for the emergence of hematopoietic stem cells (HSCs) at the aorta-gornado-mesonephro regions of the dorsal aorta. At adult stage, Notch receptors and Notch targets are expressed at different levels in diverse hematopoietic cell types and influence lineage choices. For example, Notch specifies T cell lineage over B cells. However, there has been a long-lasting debate on whether Notch signaling is required for the maintenance of adult HSCs, utilizing transgenic animals inactivating different components of the Notch signaling pathway in HSCs or niche cells. The aims of the current mini-review are to summarize the evidence that disapproves or supports such hypothesis and point at imperative questions waiting to be addressed; hence, some of the seemingly contradictory findings could be reconciled. We need to better delineate the Notch signaling events using biochemical assays to identify direct Notch targets within HSCs or niche cells in specific biological context. More importantly, we call for more elaborate studies that pertain to whether niche cell type (vascular endothelial cells or other stromal cell)-specific Notch ligands regulate the differentiation of T cells in solid tumors during the progression of T-lymphoblastic lymphoma (T-ALL) or chronic myelomonocytic leukemia (CMML). We believe that the investigation of vascular endothelial cells' or other stromal cell types' interaction with hematopoietic cells during homeostasis and stress can offer insights toward specific and effective Notch-related therapeutics.