tissue reprogramming

  • 文章类型: Journal Article
    转移性生长的关键步骤涉及产生支持癌细胞恶性行为的深度改变的微环境(生态位)。转移性生态位的复杂性在阐明驱动其起源的基础程序方面提出了重大挑战。这里,通过关注乳腺癌转移到小鼠肺部的早期阶段,我们描述了小生境内肺泡2型(AT2)细胞中癌症依赖性染色质重塑和发育程序的激活。我们表明转移细胞可以使AT2细胞进入重编程的多谱系状态。反过来,这种癌症诱导的AT2细胞重编程促进了癌细胞的干细胞样特征并增强了其启动能力.总之,我们提出了“反射干性”的概念,作为转移生态位启动过程中的早期现象,其中转移细胞将局部组织重新编程为茎样状态,从而增强内在的癌症启动潜力,创建一个正反馈循环,其中肿瘤的程序被放大。
    A key step for metastatic outgrowth involves the generation of a deeply altered microenvironment (niche) that supports the malignant behavior of cancer cells. The complexity of the metastatic niche has posed a significant challenge in elucidating the underlying programs driving its origin. Here, by focusing on early stages of breast cancer metastasis to the lung in mice, we describe a cancer-dependent chromatin remodeling and activation of developmental programs in alveolar type 2 (AT2) cells within the niche. We show that metastatic cells can prime AT2 cells into a reprogrammed multilineage state. In turn, this cancer-induced reprogramming of AT2 cells promoted stem-like features in cancer cells and enhanced their initiation capacity. In conclusion, we propose the concept of \"reflected stemness\" as an early phenomenon during metastatic niche initiation, wherein metastatic cells reprogram the local tissue into a stem-like state that enhances intrinsic cancer-initiating potential, creating a positive feedback loop where tumorigenic programs are amplified.
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  • 文章类型: Journal Article
    髓样细胞是组织中相当大比例的白细胞,包括粒细胞,单核细胞,树突状细胞,和巨噬细胞。随着各种骨髓细胞的鉴定,在稳态和疾病期间执行单独但互补的功能,我们对组织骨髓细胞的理解已经有了很大的发展。转录组学分析和命运图谱小鼠模型的令人兴奋的发现促进了对其发育起源的识别,成熟,和组织特异性专业化。这篇综述强调了目前对组织骨髓细胞的理解以及功能异质性的影响因素,以更好地理解健康或发炎组织内复杂和动态的免疫相互作用。具体来说,我们讨论了粒细胞-单核细胞祖细胞来源的吞噬细胞对组织髓系细胞异质性的贡献的新认识,以及生态位特异性因素对单核细胞和中性粒细胞表型和功能的影响.最后,我们探索炎症和疾病期间骨髓细胞异质性的发展范式。
    Myeloid cells are a significant proportion of leukocytes within tissues, comprising granulocytes, monocytes, dendritic cells, and macrophages. With the identification of various myeloid cells that perform separate but complementary functions during homeostasis and disease, our understanding of tissue myeloid cells has evolved significantly. Exciting findings from transcriptomics profiling and fate-mapping mouse models have facilitated the identification of their developmental origins, maturation, and tissue-specific specializations. This review highlights the current understanding of tissue myeloid cells and the contributing factors of functional heterogeneity to better comprehend the complex and dynamic immune interactions within the healthy or inflamed tissue. Specifically, we discuss the new understanding of the contributions of granulocyte-monocyte progenitor-derived phagocytes to tissue myeloid cell heterogeneity as well as the impact of niche-specific factors on monocyte and neutrophil phenotype and function. Lastly, we explore the developing paradigm of myeloid cell heterogeneity during inflammation and disease.
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