3273 – APELIN SIGNALING ACTS AS A MOLECULAR SWITCH BETWEEN ENDOTHELIAL AND HEMATOPOIETIC STEM CELL FATES

IF 2.7 4区医学 Q2 HEMATOLOGY

Experimental hematology Pub Date : 2026-10-01 Epub Date: 2026-10-23 DOI:10.1016/j.exphem.2026.105877

Christian Helker, Jean Eberlein, Nadja Groos

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引用次数: 0

Abstract

Hematopoietic stem and progenitor cells (HSPCs) emerge from arterial endothelial cells (ECs) through a process termed endothelial-to-hematopoietic transition (EHT), a process induced by paracrine signals and driven by a transcriptional cascade. Despite inductive signals being broadly received by ECs in the dorsal aorta (DA), only a subset of ECs undergoes EHT, whereas others maintain their vascular identity. The molecular mechanisms that determine this selective fate decision remain poorly understood. Here, we discover Apelin signaling as a critical regulator of cell fates in the DA, acting as a molecular switch to balance vascular and hematopoietic identities. We show that Apelin receptor (Aplnr)-expressing ECs retain their arterial identity, whereas Aplnr nonexpressing ECs are primed to become hemogenic endothelial cells (HECs) and transition into HSPCs. Loss of Apelin signaling leads to excessive EC-to-HEC conversion and increased HSPC numbers. Conversely, forced Aplnr expression abolishes HSPC formation by maintaining EC identity. These findings reveal that Apelin signaling regulates HSPC formation by preserving endothelial identity. In summary, our findings establish Apelin signaling as a critical regulator for balancing endothelial and hematopoietic fates.

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3273 - apelin信号作为内皮细胞和造血干细胞命运之间的分子开关

造血干细胞和祖细胞（HSPCs）由动脉内皮细胞（ECs）通过一个被称为内皮到造血转化（EHT）的过程产生，这一过程由旁分泌信号诱导并由转录级联驱动。尽管背主动脉（DA）的ECs广泛接收感应信号，但只有一部分ECs经历EHT，而其他ECs保持其血管身份。决定这种选择性命运决定的分子机制仍然知之甚少。在这里，我们发现Apelin信号是DA中细胞命运的关键调节因子，作为平衡血管和造血身份的分子开关。我们发现，表达Apelin受体（Aplnr）的内皮细胞保留了其动脉特性，而不表达applnr的内皮细胞则被诱导成为造血内皮细胞（hec）并转变为HSPCs。Apelin信号的丢失导致ec到hec的过度转化和HSPC数量的增加。相反，强制表达Aplnr通过保持EC的同一性来消除HSPC的形成。这些发现表明，Apelin信号通过保持内皮细胞身份来调节HSPC的形成。总之，我们的研究结果确立了Apelin信号作为平衡内皮和造血命运的关键调节因子。造血干细胞和祖细胞（HSPCs）由动脉内皮细胞（ECs）通过一个被称为内皮到造血转化（EHT）的过程产生，这一过程由旁分泌信号诱导并由转录级联驱动。尽管背主动脉（DA）的ECs广泛接收感应信号，但只有一部分ECs经历EHT，而其他ECs保持其血管身份。决定这种选择性命运决定的分子机制仍然知之甚少。在这里，我们发现Apelin信号是DA中细胞命运的关键调节因子，作为平衡血管和造血身份的分子开关。我们发现，表达Apelin受体（Aplnr）的内皮细胞保留了其动脉特性，而不表达applnr的内皮细胞则被诱导成为造血内皮细胞（hec）并转变为HSPCs。Apelin信号的丢失导致ec到hec的过度转化和HSPC数量的增加。相反，强制表达Aplnr通过保持EC的同一性来消除HSPC的形成。这些发现表明，Apelin信号通过保持内皮细胞身份来调节HSPC的形成。总之，我们的研究结果确立了Apelin信号作为平衡内皮和造血命运的关键调节因子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental hematology 医学-血液学

CiteScore

5.30

自引率

0.00%

发文量

审稿时长

58 days

期刊介绍： Experimental Hematology publishes new findings, methodologies, reviews and perspectives in all areas of hematology and immune cell formation on a monthly basis that may include Special Issues on particular topics of current interest. The overall goal is to report new insights into how normal blood cells are produced, how their production is normally regulated, mechanisms that contribute to hematological diseases and new approaches to their treatment. Specific topics may include relevant developmental and aging processes, stem cell biology, analyses of intrinsic and extrinsic regulatory mechanisms, in vitro behavior of primary cells, clonal tracking, molecular and omics analyses, metabolism, epigenetics, bioengineering approaches, studies in model organisms, novel clinical observations, transplantation biology and new therapeutic avenues.