德国明斯特大学Ralf H. Adams团队近期研究表明，Apelin阳性内皮微环境细胞在清髓性损伤后调控造血并介导血管再生。这一研究成果2019年11月21日在线发在国际学术期刊《细胞—干细胞》上。

研究人员发现，在响应放疗和其他治疗后造血细胞本身的丢失，能够触发血管扩张、通透性和内皮细胞（EC）增殖。研究人员进一步确定了表达Apelin（Apln阳性）EC的小亚群，其占据骨髓细胞的0.003％，这对于生理稳态和移植诱导的骨髓再生至关重要。Apln阳性EC的遗传敲除或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。同样地，Apln阳性EC的比例在辐射后显著增加，并响应由移植的造血干细胞和祖细胞（HSPC）提供的VEGF-A来促进骨血管系统的正常化。总之，这些发现揭示了造血干细胞在维持血管完整性和Apln阳性EC造血过程中的关键功能，并提示了改善骨髓移植的潜在靶标。

据悉，放射疗法和化学疗法破坏了骨骼的血管系统，但使骨髓移植后血管再生的根本原因和机制仍知之甚少。

附：英文原文

Title: Apelin+ Endothelial Niche Cells Control Hematopoiesis and Mediate Vascular Regeneration after Myeloablative Injury

Author: Qi Chen, Yang Liu, Hyun-Woo Jeong, Martin Stehling, Van Vuong Dinh, Bin Zhou, Ralf H. Adams

Issue&Volume: November 21, 2019

Abstract: 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.

DOI: 10.1016/j.stem.2019.10.006

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30427-8