Transcriptional analysis of fracture healing and the induction of embryonic stem cell-related genes.
Transcriptional analysis of fracture healing and the induction of embryonic stem cell-related genes.
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DOI：
10.1371/journal.pone.0005393
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Gerstenfeld LC
中科院分区：
文献类型：
--
作者：
Bais M;McLean J;Sebastiani P;Young M;Wigner N;Smith T;Kotton DN;Einhorn TA;Gerstenfeld LC
骨折是最常见的人类创伤之一。骨折愈合代表了一种独特的暂时可定义的产后过程，在该过程中研究调节软骨内骨骼组织形成的多个分子事件的复杂相互作用。由于骨折愈合的再生性质，据推测，大量出生后干细胞被募集并有助于形成有助于这一过程的多种细胞谱系。贝叶斯模型用于生成骨折愈合过程中转录组的时间分布。与各种生物、代谢和调节途径相关的本体之间的时间关系已被确定，并且与骨骼发生、血管发生和神经发生相关的发育过程相关。所有表达的 BMP、Wnt、FGF 及其受体的互补体与骨折愈合过程中同时表达的转录因子子集相关。我们进一步定义了骨折愈合期间已知与人类遗传性骨骼疾病相关的 193 个基因中的 174 个基因的时间表达模式。为了确定骨折愈合期间招募的干细胞与其他类型干细胞可能存在的共同调控特征，我们对照胚胎干细胞（ESC）和间充质干细胞（MSC）中的转录组查询了骨折愈合的转录组。大约 300 个在 ESC 中优先表达的已知基因和约 350 个在 MSC 中优先表达的已知基因在骨折愈合过程中表现出诱导作用。 Nanog 是与 ESC 干细胞维持相关的中央表观遗传调节因子之一，已被证明与多种形式的骨修复以及 MSC 分化相关。总之，这些数据首次对骨折愈合过程中发生的软骨内骨形成过程的转录组进行了时间分析。他们表明神经发生和血管发生是骨骼组织形成的主要组成部分，并表明出生后干细胞和 ESC 中的干细胞共享共同的途径。
Fractures are among the most common human traumas. Fracture healing represents a unique temporarily definable post-natal process in which to study the complex interactions of multiple molecular events that regulate endochondral skeletal tissue formation. Because of the regenerative nature of fracture healing, it is hypothesized that large numbers of post-natal stem cells are recruited and contribute to formation of the multiple cell lineages that contribute to this process. Bayesian modeling was used to generate the temporal profiles of the transcriptome during fracture healing. The temporal relationships between ontologies that are associated with various biologic, metabolic, and regulatory pathways were identified and related to developmental processes associated with skeletogenesis, vasculogenesis, and neurogenesis. The complement of all the expressed BMPs, Wnts, FGFs, and their receptors were related to the subsets of transcription factors that were concurrently expressed during fracture healing. We further defined during fracture healing the temporal patterns of expression for 174 of the 193 genes known to be associated with human genetic skeletal disorders. In order to identify the common regulatory features that might be present in stem cells that are recruited during fracture healing to other types of stem cells, we queried the transcriptome of fracture healing against that seen in embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs). Approximately 300 known genes that are preferentially expressed in ESCs and ∼350 of the known genes that are preferentially expressed in MSCs showed induction during fracture healing. Nanog, one of the central epigenetic regulators associated with ESC stem cell maintenance, was shown to be associated in multiple forms or bone repair as well as MSC differentiation. In summary, these data present the first temporal analysis of the transcriptome of an endochondral bone formation process that takes place during fracture healing. They show that neurogenesis as well as vasculogenesis are predominant components of skeletal tissue formation and suggest common pathways are shared between post-natal stem cells and those seen in ESCs.
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影响因子：
15.8
作者：
Barberi T;Willis LM;Socci ND;Studer L
通讯作者：
Studer L
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作者：
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通讯作者：
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作者：
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通讯作者：
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