C‐X‐C motif chemokine ligand 12 (CXCL12; aka SDF1α) is a major regulator of a number of cellular systems, including hematopoiesis, where it influences hematopoietic cell trafficking, proliferation, and survival during homeostasis and upon stress and disease. A variety of constitutive, temporal, ubiquitous, and cell‐specific loss‐of‐function models have documented the functional consequences on hematopoiesis upon deletion of Cxcl12. Here, in contrast to loss‐of‐function experiments, we implemented a gain‐of‐function approach by generating a doxycycline‐inducible transgenic mouse model that enables spatial and temporal overexpression of Cxcl12. We demonstrated that ubiquitous CXCL12 overexpression led to an increase in multipotent progenitors in the bone marrow and spleen. The CXCL12+ mice displayed reduced reconstitution potential as either donors or recipients in transplantation experiments. Additionally, we discovered that Cxcl12 overexpression improved hematopoietic stem and progenitor cell mobilization into the blood, and conferred radioprotection by promoting quiescence. Thus, this new CXCL12+ mouse model provided new insights into major facets of hematopoiesis and serves as a versatile resource for studying CXCL12 function in a variety of contexts.

中文翻译：

---

CXCL12 的普遍过表达赋予辐射保护并增强造血干细胞和祖细胞的动员

C-X-C 基序趋化因子配体 12（CXCL12；又名 SDF1α）是许多细胞系统的主要调节剂，包括造血系统，它在体内平衡和压力和疾病期间影响造血细胞运输、增殖和存活。各种组成型、时间性、普遍性和细胞特异性功能丧失模型已经记录了 Cxcl12 缺失对造血功能的影响。在这里，与功能丧失实验相反，我们通过生成强力霉素诱导的转基因小鼠模型来实现功能获得方法，该模型能够实现 Cxcl12 的空间和时间过表达。我们证明了无处不在的 CXCL12 过表达导致骨髓和脾脏中多能祖细胞的增加。在移植实验中，CXCL12+ 小鼠作为供体或受体的重建潜力降低。此外，我们发现 Cxcl12 过表达改善了造血干细胞和祖细胞向血液中的动员，并通过促进静止来赋予辐射防护。因此，这种新的 CXCL12+ 小鼠模型为造血的主要方面提供了新的见解，并作为在各种情况下研究 CXCL12 功能的多功能资源。