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Uncovering the stem cell hierarchy by genetic lineage tracing in the mammary gland

机译:通过遗传谱系追踪发现乳腺中的干细胞等级

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The mammary gland is the distinct feature that gives the name to the class of mammals and distinguishes them from other animals. Functionally, the mammary gland is a secretory organ which main role is to produce milk to nourish the offspring. Organogenesis of the mammary gland starts during embryogenesis but occurs mainly after birth at puberty under the influence of hormonal cues. Throughout the adult life as well as during pregnancy, the mammary gland shows a remarkable regenerative ability, thus constituting an excellent model for studying stem cell biology. Although the mammary gland consists of a relatively simple epithelial structure with a luminal and a basal cell layers, these are indeed composed by distinct subsets of mammary epithelial cells. Flow cytometry and transplantation assay have identified several subpopulations of stem and/or progenitor cells in the mammary gland. Yet, physiological and developmental relevant information can only be obtained when investigating the stem cell hierarchy in the intact mammary gland. Genetic lineage tracing studies have offered unprecedented levels of information regarding the organization of the stem cell compartment and possible role of resident stem and/or progenitor cells at different stages of the mammary gland organogenesis. These studies, although creating a passionate debate, highlight the existence of heterogeneous stem cell compartment, where bipotent as well as unipotent mammary stem cells seems to co-exist. Genetic lineage tracing experiments provide relevant information on stem cells that are key for understanding both normal development as well as associated pathologies in human. It holds the promise of providing new insights into the cell-of-origin and heterogeneity of breast tumorigenesis.
机译:乳腺是一种独特的特征,它使哺乳动物类具有名称,并将它们与其他动物区分开来。在功能上,乳腺是一种分泌器官,其主要作用是生产牛奶以滋养后代。乳腺的器官发生在胚胎发生期间开始,但主要发生在青春期出生后在激素提示的影响下。在整个成年以及怀孕期间,乳腺均具有出色的再生能力,因此构成了研究干细胞生物学的极佳模型。尽管乳腺由具有腔和基底细胞层的相对简单的上皮结构组成,但这些确实由乳腺上皮细胞的不同子集组成。流式细胞术和移植测定法已经确定了乳腺中干细胞和/或祖细胞的几个亚群。但是,只有在研究完整乳腺中的干细胞层次时才能获得生理和发育方面的相关信息。遗传谱系追踪研究已经提供了有关干细胞区室的组织以及驻留的干细胞和/或祖细胞在乳腺器官发生不同阶段可能发挥的作用的前所未有的信息水平。这些研究尽管引起了激烈的争论,但突显了异质干细胞区室的存在,其中双能和单能乳腺干细胞似乎共存。遗传谱系追踪实验提供了有关干细胞的相关信息,这对于理解人类的正常发育以及相关的病理学至关重要。它有望为乳腺肿瘤发生的起源细胞和异质性提供新的见解。

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