The transcription factor Sox2 is required for osteoblast self-renewal.
The transcription factor Sox2 is required for osteoblast self-renewal.
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DOI：
10.1038/cdd.2010.57
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发表时间：
2010-08
影响因子：
12.4
通讯作者：
中科院分区：
文献类型：
--
作者：
大多数组织和器官的发育和维持需要多能和单能干细胞的存在，这些干细胞具有自我更新以及产生定向的、进一步分化的细胞类型的能力。转录因子Sox 2对胚胎发育至关重要，并维持胚胎干细胞的多能性和自我更新。它在体外和体内在未成熟成骨细胞/骨祖细胞中表达，并由FGF信号传导诱导，其刺激成骨细胞增殖并抑制分化。Sox 2过表达本身可抑制成骨细胞分化。为了阐明其在成骨细胞谱系中的作用，我们用成骨细胞特异性Cre介导的Sox 2敲除产生小鼠。这些小鼠体型小，骨质减少，Sox 2失活呈马赛克状。然而，将突变小鼠的颅骨成骨细胞培养2-3代未能产生任何Sox 2缺失细胞。在培养的成骨细胞中通过Cre介导的切除使Sox 2基因失活，表明Sox 2无效细胞不能在培养中反复传代，不能形成集落，并以衰老表型阻止其生长。此外，在独立的成骨细胞系中Sox 2特异性shRNA的表达抑制了它们的增殖能力。能够形成“骨球”的成骨细胞在Sox 2表达中大大富集。这些数据确定了Sox 2在维持成骨细胞谱系自我更新中的新作用。
The development and maintenance of most tissues and organs requires the presence of multipotent and unipotent stem cells that have the ability of self-renewal as well as of generating committed, further differentiated cell types. The transcription factor Sox2 is essential for embryonic development and maintains pluripotency and self-renewal in embryonic stem cells. It is expressed in immature osteoblasts/osteoprogenitors in vitro and in vivo and is induced by FGF signaling, which stimulates osteoblast proliferation and inhibits differentiation. Sox2 overexpression can by itself inhibit osteoblast differentiation. To elucidate its role in the osteoblastic lineage, we generated mice with an osteoblast-specific, Cre-mediated knockout of Sox2. These mice are small and osteopenic, and mosaic for Sox2 inactivation. However, culturing calvarial osteoblasts from the mutant mice for 2-3 passages failed to yield any Sox2 null cells. Inactivation of the Sox2 gene by Cre-mediated excision in cultured osteoblasts showed that Sox2 null cells could not survive repeated passage in culture, could not form colonies, and arrested their growth with a senescent phenotype. Additionally, expression of Sox2 specific shRNAs in independent osteoblastic cell lines suppressed their proliferative ability. Osteoblasts capable of forming “osteospheres” are greatly enriched in Sox2 expression. These data identify a novel role for Sox2 in the maintenance of self-renewal in the osteoblastic lineage.
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DOI：
10.1083/jcb.200409182
发表时间：
2005-03-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mansukhani A;Ambrosetti D;Holmes G;Cornivelli L;Basilico C
通讯作者：
Basilico C
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
6.2
作者：
Dunstan, CR;Boyce, R;Mundy, GR
通讯作者：
Mundy, GR
影响因子：
25
作者：
Favaro, Rebecca;Valotta, Menella;Nicolis, Silvia K.
通讯作者：
Nicolis, Silvia K.
影响因子：
64.5
作者：
Nakashima, K;Zhou, X;de Crombrugghe, B
通讯作者：
de Crombrugghe, B