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重组肢体分析作为类器官模型

Recombinant Limb Assay as Organoid Model.

作者信息

García-García Roberto Damián, Garay-Pacheco Estefanía, Marín-Llera Jessica Cristina, Chimal-Monroy Jesús

机构信息

Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de México, México.

出版信息

Front Cell Dev Biol. 2022 Apr 26;10:863140. doi: 10.3389/fcell.2022.863140. eCollection 2022.

DOI:10.3389/fcell.2022.863140
PMID:35557939
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9086426/
Abstract

Organ formation initiates once cells become committed to one of the three embryonic germ layers. In the early stages of embryogenesis, different gene transcription networks regulate cell fate after each germ layer is established, thereby directing the formation of complex tissues and functional organs. These events can be modeled by creating organoids from induced pluripotent, embryonic, or adult stem cells to study organ formation. Under these conditions, the induced cells are guided down the developmental pathways as in embryonic development, resulting in an organ of a smaller size that possesses the essential functions of the organ of interest. Although organoids are widely studied, the formation of skeletal elements in an organoid model has not yet been possible. Therefore, we suggest that the formation of skeletal elements using the recombinant limb (RL) assay system can serve as an organoid model. RLs are formed from undissociated or dissociated-reaggregated undifferentiated mesodermal cells introduced into an ectodermal cover obtained from an early limb bud. Next, this filled ectoderm is grafted into the back of a donor chick embryo. Under these conditions, the cells can receive the nascent embryonic signals and develop complex skeletal elements. We propose that the formation of skeletal elements induced through the RL system may occur from stem cells or other types of progenitors, thus enabling the study of morphogenetic properties from these cells for the first time.

摘要

一旦细胞分化为三个胚胎胚层之一,器官形成便开始了。在胚胎发生的早期阶段,不同的基因转录网络在每个胚层形成后调节细胞命运,从而指导复杂组织和功能器官的形成。这些过程可以通过从诱导多能干细胞、胚胎干细胞或成体干细胞创建类器官来模拟,以研究器官形成。在这些条件下,诱导细胞会像在胚胎发育中一样沿着发育途径分化,形成尺寸较小但具备目标器官基本功能的器官。尽管类器官已得到广泛研究,但在类器官模型中尚未实现骨骼元素的形成。因此,我们认为利用重组肢体(RL)检测系统形成骨骼元素可作为一种类器官模型。RL由未解离或解离后重新聚集的未分化中胚层细胞形成,这些细胞被引入从早期肢芽获得的外胚层覆盖物中。接下来,将这种填充了细胞的外胚层移植到供体鸡胚的背部。在这些条件下,细胞能够接收新生的胚胎信号并发育出复杂的骨骼元素。我们提出,通过RL系统诱导形成的骨骼元素可能源自干细胞或其他类型的祖细胞,从而首次能够研究这些细胞的形态发生特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cfe/9086426/e72cdcd8a2cb/fcell-10-863140-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cfe/9086426/9641569b7f47/fcell-10-863140-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cfe/9086426/e72cdcd8a2cb/fcell-10-863140-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cfe/9086426/9641569b7f47/fcell-10-863140-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cfe/9086426/e72cdcd8a2cb/fcell-10-863140-g002.jpg

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Dev Cell. 2024 Feb 5;59(3):415-430.e8. doi: 10.1016/j.devcel.2023.12.010.
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Methods for vascularization and perfusion of tissue organoids.组织类器官的血管生成和灌注方法。
Mamm Genome. 2022 Sep;33(3):437-450. doi: 10.1007/s00335-022-09951-2. Epub 2022 Mar 25.
3
Chicken Recombinant Limbs Assay to Understand Morphogenesis, Patterning, and Early Steps in Cell Differentiation.鸡的重组肢体分析,用于研究形态发生、模式形成以及细胞分化的早期步骤。
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Deciphering the spatial-temporal transcriptional landscape of human hypothalamus development.解析人类下丘脑发育的时空转录图谱。
Cell Stem Cell. 2022 Feb 3;29(2):328-343.e5. doi: 10.1016/j.stem.2021.11.009. Epub 2021 Dec 7.
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The Organizer and Its Signaling in Embryonic Development.胚胎发育中的组织者及其信号传导
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SMAD4 target genes are part of a transcriptional network that integrates the response to BMP and SHH signaling during early limb bud patterning.SMAD4 的靶基因是一个转录网络的一部分,该网络整合了早期肢芽模式形成过程中 BMP 和 SHH 信号的反应。
Development. 2021 Dec 1;148(23). doi: 10.1242/dev.200182. Epub 2021 Dec 3.
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Tracing the skeletal progenitor transition during postnatal bone formation.追踪出生后骨形成过程中的骨骼祖细胞过渡。
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