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Emilin-2 是骨髓细胞外基质的一个组成部分,调节间充质干细胞的分化和造血祖细胞。

Emilin-2 is a component of bone marrow extracellular matrix regulating mesenchymal stem cell differentiation and hematopoietic progenitors.

机构信息

SOSd Cell Stem Unit, Department of Translational Research, National Cancer Center CRO-IRCSS, 33081, Aviano, Italy.

Department of Molecular Medicine, University of Padova, Via Ugo Bassi 58/B, 35131, Padova, Italy.

出版信息

Stem Cell Res Ther. 2022 Jan 10;13(1):2. doi: 10.1186/s13287-021-02674-2.

DOI:10.1186/s13287-021-02674-2
PMID:35012633
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8744352/
Abstract

BACKGROUND

Dissection of mechanisms involved in the regulation of bone marrow microenvironment through cell-cell and cell-matrix contacts is essential for the detailed understanding of processes underlying bone marrow activities both under physiological conditions and in hematologic malignancies. Here we describe Emilin-2 as an abundant extracellular matrix component of bone marrow stroma.

METHODS

Immunodetection of Emilin-2 was performed in bone marrow sections of mice from 30 days to 6 months of age. Emilin-2 expression was monitored in vitro in primary and mesenchymal stem cell lines under undifferentiated and adipogenic conditions. Hematopoietic stem cells and progenitors in bone marrow of 3- to 10-month-old wild-type and Emilin-2 null mice were analyzed by flow cytometry.

RESULTS

Emilin-2 is deposited in bone marrow extracellular matrix in an age-dependent manner, forming a meshwork that extends from compact bone boundaries to the central trabecular regions. Emilin-2 is expressed and secreted by both primary and immortalized bone marrow mesenchymal stem cells, exerting an inhibitory action in adipogenic differentiation. In vivo Emilin-2 deficiency impairs the frequency of hematopoietic stem/progenitor cells in bone marrow during aging.

CONCLUSION

Our data provide new insights in the contribution of bone marrow extracellular matrix microenvironment in the regulation of stem cell niches and hematopoietic progenitor differentiation.

摘要

背景

通过细胞-细胞和细胞-基质接触来剖析骨髓微环境调节机制对于深入了解生理条件下和血液恶性肿瘤中骨髓活动的过程至关重要。在这里,我们将 Emilin-2 描述为骨髓基质丰富的细胞外基质成分。

方法

在 30 天至 6 个月龄的小鼠骨髓切片中进行 Emilin-2 的免疫检测。在未分化和脂肪生成条件下,监测原代和间充质干细胞系中 Emilin-2 的表达情况。通过流式细胞术分析 3 至 10 个月龄野生型和 Emilin-2 缺失型小鼠骨髓中的造血干细胞和祖细胞。

结果

Emilin-2 随年龄呈依赖性沉积在骨髓细胞外基质中,形成从密质骨边界延伸到中央小梁区域的网格状结构。Emilin-2 由原代和永生化骨髓间充质干细胞表达和分泌,在脂肪生成分化中发挥抑制作用。体内 Emilin-2 缺乏会在衰老过程中损害骨髓中造血干细胞/祖细胞的频率。

结论

我们的数据为骨髓细胞外基质微环境在调节干细胞龛和造血祖细胞分化中的作用提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541e/8744352/475f589cd9d4/13287_2021_2674_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541e/8744352/c8ec854585cc/13287_2021_2674_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541e/8744352/302b792eb523/13287_2021_2674_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541e/8744352/f788817e86c0/13287_2021_2674_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541e/8744352/5594d4d0ce4c/13287_2021_2674_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541e/8744352/43ba6d7d3a4c/13287_2021_2674_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541e/8744352/475f589cd9d4/13287_2021_2674_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541e/8744352/c8ec854585cc/13287_2021_2674_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541e/8744352/302b792eb523/13287_2021_2674_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541e/8744352/f788817e86c0/13287_2021_2674_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541e/8744352/5594d4d0ce4c/13287_2021_2674_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541e/8744352/43ba6d7d3a4c/13287_2021_2674_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/541e/8744352/475f589cd9d4/13287_2021_2674_Fig7_HTML.jpg

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