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骨细胞系中的 N-钙黏蛋白对于维持造血干细胞并非必需。

N-cadherin in osteolineage cells is not required for maintenance of hematopoietic stem cells.

机构信息

Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.

出版信息

Blood. 2012 Jul 12;120(2):295-302. doi: 10.1182/blood-2011-09-377457. Epub 2012 Feb 9.

DOI:10.1182/blood-2011-09-377457
PMID:22323481
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3398761/
Abstract

There is evidence suggesting that N-cadherin expression on osteoblast lineage cells regulates hematopoietic stem cell (HSC) function and quiescence. To test this hypothesis, we conditionally deleted N-cadherin (Cdh2) in osteoblasts using Cdh2(flox/flox) Osx-Cre mice. N-cadherin expression was efficiently ablated in osteoblast lineage cells as assessed by mRNA expression and immunostaining of bone sections. Basal hematopoiesis is normal in these mice. In particular, HSC number, cell cycle status, long-term repopulating activity, and self-renewal capacity were normal. Moreover, engraftment of wild-type cells into N-cadherin-deleted recipients was normal. Finally, these mice responded normally to G-CSF, a stimulus that mobilizes HSCs by inducing alterations to the stromal micro-environment. In conclusion, N-cadherin expression in osteoblast lineage cells is dispensable for HSC maintenance in mice.

摘要

有证据表明,成骨细胞系细胞上的 N-钙黏蛋白表达调节造血干细胞(HSC)的功能和静止状态。为了验证这一假说,我们使用 Cdh2(flox/flox) Osx-Cre 小鼠在成骨细胞中条件性缺失 N-钙黏蛋白(Cdh2)。通过 mRNA 表达和骨切片免疫染色评估,成骨细胞系细胞中的 N-钙黏蛋白表达被有效消除。这些小鼠的基础造血功能正常。特别是,HSC 数量、细胞周期状态、长期重殖活性和自我更新能力正常。此外,野生型细胞植入 N-钙黏蛋白缺失的受体中是正常的。最后,这些小鼠对 G-CSF 反应正常,G-CSF 通过诱导基质微环境的改变来动员 HSC。总之,成骨细胞系细胞中 N-钙黏蛋白的表达对于维持小鼠的 HSC 是可有可无的。

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本文引用的文献

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Connexin43 deficiency reduces the sensitivity of cortical bone to the effects of muscle paralysis.缝隙连接蛋白 43 缺乏降低皮质骨对肌肉麻痹作用的敏感性。
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Osteoblast connexin43 modulates skeletal architecture by regulating both arms of bone remodeling.成骨细胞连接蛋白 43 通过调节骨重塑的两个分支来调节骨骼结构。
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Cadherin-based adhesion is a potential target for niche manipulation to protect hematopoietic stem cells in adult bone marrow.基于钙黏蛋白的黏附作用是调控骨髓微环境以保护成体骨髓造血干细胞的一个潜在靶点。
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