Apelin+ Endothelial Niche Cells Control Hematopoiesis and Mediate Vascular Regeneration after Myeloablative Injury
Apelin+ Endothelial Niche Cells Control Hematopoiesis and Mediate Vascular Regeneration after Myeloablative Injury
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DOI：
10.1016/j.stem.2019.10.006
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发表时间：
2019-12-05
期刊：
影响因子：
23.9
通讯作者：
Adams, Ralf H.
中科院分区：
文献类型：
--
作者：
Chen, Qi;Liu, Yang;Adams, Ralf H.
放疗和化疗破坏骨血管，但骨髓移植后血管再生的潜在原因和机制仍然知之甚少。在这里，我们表明，由于照射和其他治疗，造血细胞本身的损失会引发血管扩张、通透性和内皮细胞（EC）增殖。我们进一步鉴定了一小群表达apelin （Apln(+)）的内皮细胞，占骨髓细胞的0.003%，这对生理稳态和移植诱导的骨髓再生至关重要。appln ECs的基因消融或apin - creer介导的Kitl和Vegfr2的缺失会破坏造血干细胞（HSC）的维持和再生。与此一致的是，照射后appln (+) ECs的比例显著增加，并促进骨血管对VEGF-A的正常化，VEGF-A是由移植的造血干细胞和祖细胞（HSPCs）提供的。总之，这些发现揭示了HSPCs在维持血管完整性和Apln(+) ECs在造血中的关键功能作用，提示了改善骨髓移植的潜在靶点。
Radiotherapy and chemotherapy disrupt bone vasculature, but the underlying causes and mechanisms enabling vessel regeneration after bone marrow (BM) transplantation remain poorly understood. Here, we show that loss of hematopoietic cells per se, in response to irradiation and other treatments, triggers vessel dilation, permeability, and endothelial cell (EC) proliferation. We further identify a small subpopulation of Apelin-expressing (Apln(+)) ECs, representing 0.003% of BM cells, that is critical for physiological homeostasis and transplant-induced BM regeneration. Genetic ablation of Apln ECs or Apin-CreER-mediated deletion of Kitl and Vegfr2 disrupt hematopoietic stem cell (HSC) maintenance and contributions to regeneration. Consistently, the fraction of Apln(+) ECs increases substantially after irradiation and promotes normalization of the bone vasculature in response to VEGF-A, which is provided by transplanted hematopoietic stem and progenitor cells (HSPCs). Together, these findings reveal critical functional roles for HSPCs in maintaining vascular integrity and for Apln(+) ECs in hematopoiesis, suggesting potential targets for improving BM transplantation.