Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Blood. 2012 Jul 12;120(2):295-302. doi: 10.1182/blood-2011-09-377457. Epub 2012 Feb 9.
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.
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。