Osterix-cre labeled progenitor cells contribute to the formation and maintenance of the bone marrow stroma.

Osterix-cre labeled progenitor cells contribute to the formation and maintenance of the bone marrow stroma.
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DOI:
10.1371/journal.pone.0071318
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Maye P
Maye P
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu Y;Strecker S;Wang L;Kronenberg MS;Wang W;Rowe DW;Maye P

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我们使用 Osterix-EGFPCre 和 Osterix-CreERt 动物模型进行了命运图谱研究,发现 Cre 报告基因在构成骨髓基质的许多不同细胞类型中表达。组成型命运图谱导致对位于整个骨髓中的不同细胞成分进行标记,而 E14.5 处的时间命运图谱则导致对骨髓区域内的细胞进行标记。由组成性和时间命运图谱标记的细胞类型的身份包括成骨细胞、脂肪细胞、血管平滑肌、神经周围细胞和基质细胞。对 E14.5dpc 标记的胚胎前体细胞的长期追踪显示,其后代持续存在长达 10 个月,这表明命运图谱、标记的胚胎前体细胞产生了长寿的骨髓祖细胞。为了为骨髓祖细胞的标记提供进一步的证据,来自 Osterix-EGFPCre/Ai9 小鼠的骨髓培养物显示,基质细胞保留了 Cre 报告基因表达,并产生了 FACS 分选的群体,该群体能够在体外分化为成骨细胞、脂肪细胞和软骨细胞,并能够分化为成骨细胞、脂肪细胞和成骨细胞。 移植后的血管周围基质细胞。总的来说,我们的研究揭示了 Osterix-Cre 标记的胚胎祖细胞产生成体骨髓祖细胞的发育过程,从而建立和维持骨髓基质。
We have carried out fate mapping studies using Osterix-EGFPCre and Osterix-CreERt animal models and found Cre reporter expression in many different cell types that make up the bone marrow stroma. Constitutive fate mapping resulted in the labeling of different cellular components located throughout the bone marrow, whereas temporal fate mapping at E14.5 resulted in the labeling of cells within a region of the bone marrow. The identity of cell types marked by constitutive and temporal fate mapping included osteoblasts, adipocytes, vascular smooth muscle, perineural, and stromal cells. Prolonged tracing of embryonic precursors labeled at E14.5dpc revealed the continued existence of their progeny up to 10 months of age, suggesting that fate mapped, labeled embryonic precursors gave rise to long lived bone marrow progenitor cells. To provide further evidence for the marking of bone marrow progenitors, bone marrow cultures derived from Osterix-EGFPCre/Ai9 mice showed that stromal cells retained Cre reporter expression and yielded a FACS sorted population that was able to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro and into osteoblasts, adipocytes, and perivascular stromal cells after transplantation. Collectively, our studies reveal the developmental process by which Osterix-Cre labeled embryonic progenitors give rise to adult bone marrow progenitors which establish and maintain the bone marrow stroma.
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