IGF1R signaling in perinatal mesenchymal stem cells determines definitive hematopoiesis in bone marrow.

IF 21 1区医学 Q1 HEMATOLOGY

Blood Pub Date : 2024-10-22 DOI:10.1182/blood.2024024258

Qi Lou,Kaizheng Jiang,Xiaoqi Wang,Yuan Pan,Guo Qiu,Binghuo Wu,Lisha Yuan,Siyu Xie,Jian Chen,Quanhui Xu,Meng Zhao,Linjia Jiang

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引用次数: 0

Abstract

During the transition from embryonic to adult life, the sites of hematopoiesis undergo dynamic shifts across various tissues. In adults, while bone marrow becomes the primary site for definitive hematopoiesis, the establishment of the bone marrow niche for accommodating hematopoietic stem cells (HSCs) remains incompletely understood. Here, we reveal that perinatal bone marrow mesenchymal stem cells (BMSCs) exhibit highly activated insulin-like growth factor 1 receptor (IGF1R) signaling compared to adult BMSCs. Deletion of Igf1r in perinatal BMSCs hinders the transition of HSCs from the fetal liver to the bone marrow in perinatal mice and disrupts hematopoiesis in adult individuals. Conversely, the deletion of Igf1r in adult BMSCs, adipocytes, osteoblasts, or endothelial cells does not affect HSCs in the bone marrow. Mechanistically, IGF1R signaling activates the transcription factor nuclear factor of activated T cells c1 (NFATc1) in perinatal BMSCs, which upregulates CXCL12 and other niche factors for HSC retention. Overall, IGF1R signaling in perinatal BMSCs regulates the development of the bone marrow niche for hematopoiesis.

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围产期间充质干细胞中的 IGF1R 信号决定骨髓中的最终造血。

在从胚胎到成年的过渡时期，造血部位会在不同组织间发生动态变化。成年后，骨髓成为确定性造血的主要部位，但人们对容纳造血干细胞（HSCs）的骨髓生态位的建立仍不甚了解。在这里，我们发现与成体骨髓间充质干细胞相比，围产期骨髓间充质干细胞（BMSCs）表现出高度活化的胰岛素样生长因子1受体（IGF1R）信号传导。围产期间充质干细胞中Igf1r的缺失阻碍了围产期小鼠造血干细胞从胎儿肝脏向骨髓的过渡，并破坏了成年个体的造血功能。相反，在成年 BMSCs、脂肪细胞、成骨细胞或内皮细胞中缺失 Igf1r 不会影响骨髓中的造血干细胞。从机理上讲，IGF1R 信号激活了围产期 BMSCs 中的活化 T 细胞核因子 c1（NFATc1）转录因子，从而上调了 CXCL12 和其他有利于造血干细胞保留的生态位因子。总之，围产期 BMSCs 中的 IGF1R 信号调节骨髓造血生态位的发育。

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

Blood 医学-血液学

CiteScore

23.60

自引率

3.90%

发文量

955

审稿时长

1 months

期刊介绍： Blood, the official journal of the American Society of Hematology, published online and in print, provides an international forum for the publication of original articles describing basic laboratory, translational, and clinical investigations in hematology. Primary research articles will be published under the following scientific categories: Clinical Trials and Observations; Gene Therapy; Hematopoiesis and Stem Cells; Immunobiology and Immunotherapy scope; Myeloid Neoplasia; Lymphoid Neoplasia; Phagocytes, Granulocytes and Myelopoiesis; Platelets and Thrombopoiesis; Red Cells, Iron and Erythropoiesis; Thrombosis and Hemostasis; Transfusion Medicine; Transplantation; and Vascular Biology. Papers can be listed under more than one category as appropriate.