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Apelin+ Endothelial Niche Cells Control Hematopoiesis and Mediate Vascular Regeneration after Myeloablative Injury.
Cell Stem Cell ( IF 19.8 ) Pub Date : 2019-11-21 , DOI: 10.1016/j.stem.2019.10.006
Qi Chen 1 , Yang Liu 1 , Hyun-Woo Jeong 1 , Martin Stehling 2 , Van Vuong Dinh 1 , Bin Zhou 3 , Ralf H Adams 1
Affiliation  

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 Apln-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.

中文翻译:

Apelin +内皮小生境细胞控制造血功能并介导清髓性损伤后介导的血管再生。

放射疗法和化学疗法破坏了骨骼的血管系统,但使骨髓(BM)移植后血管再生的根本原因和机制仍知之甚少。在这里,我们表明响应辐射和其他治疗,造血细胞本身的损失会触发血管扩张,通透性和内皮细胞(EC)增殖。我们进一步确定了表达Apelin(Apln +)EC的小亚群,代表BM细胞的0.003%,这对于生理稳态和移植物诱导的BM再生至关重要。Apln + EC的遗传消融或Apln-CreER介导的Kit1和Vegfr2缺失会破坏造血干细胞(HSC)的维持并促进再生。始终如一 辐射后,Apln + EC的比例显着增加,并响应由移植的造血干细胞和祖细胞(HSPC)提供的VEGF-A促进骨脉管系统的正常化。在一起,这些发现揭示了造血干细胞在维持血管完整性和Apln + ECs的关键功能中起着关键作用,表明了改善BM移植的潜在目标。
更新日期:2019-11-22
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