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NOTO 转录因子指导人诱导多能干细胞衍生的中胚层祖细胞向脊索命运分化。

NOTO Transcription Factor Directs Human Induced Pluripotent Stem Cell-Derived Mesendoderm Progenitors to a Notochordal Fate.

机构信息

INSERM UMR 1229, RMeS, Université de Nantes, ONIRIS, F-44042 Nantes, France.

CHU Nantes, PHU 4 OTONN, F-44042 Nantes, France.

出版信息

Cells. 2020 Feb 24;9(2):509. doi: 10.3390/cells9020509.

DOI:10.3390/cells9020509
PMID:32102328
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7072849/
Abstract

The founder cells of the Nucleus pulposus, the centre of the intervertebral disc, originate in the embryonic notochord. After birth, mature notochordal cells (NC) are identified as key regulators of disc homeostasis. Better understanding of their biology has great potential in delaying the onset of disc degeneration or as a regenerative-cell source for disc repair. Using human pluripotent stem cells, we developed a two-step method to generate a stable NC-like population with a distinct molecular signature. Time-course analysis of lineage-specific markers shows that WNT pathway activation and transfection of the notochord-related transcription factor NOTO are sufficient to induce high levels of mesendoderm progenitors and favour their commitment toward the notochordal lineage instead of paraxial and lateral mesodermal or endodermal lineages. This study results in the identification of NOTO-regulated genes including some that are found expressed in human healthy disc tissue and highlights NOTO function in coordinating the gene network to human notochord differentiation.

摘要

椎间盘中心的髓核创始细胞起源于胚胎脊索。出生后，成熟的脊索细胞 (NC) 被认为是调节椎间盘内稳态的关键因素。更好地了解它们的生物学特性具有延迟椎间盘退变发生或作为椎间盘修复的再生细胞来源的巨大潜力。我们使用人多能干细胞开发了一种两步法，可生成具有独特分子特征的稳定的 NC 样细胞群。谱系特异性标志物的时程分析表明，WNT 通路的激活和脊索相关转录因子 NOTO 的转染足以诱导高水平的中胚层祖细胞，并促使它们向脊索谱系分化，而不是向轴旁中胚层和侧中胚层或内胚层谱系分化。这项研究确定了 NOTO 调节的基因，包括一些在人健康椎间盘组织中表达的基因，并强调了 NOTO 在协调基因网络以实现人脊索分化中的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/4a3872717580/cells-09-00509-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/c130c4fc69c6/cells-09-00509-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/a776f6064df8/cells-09-00509-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/1e9cbcdd7760/cells-09-00509-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/c359030a305e/cells-09-00509-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/9c6e581c33a7/cells-09-00509-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/e7a0f8561d9f/cells-09-00509-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/4e7fa7c08d87/cells-09-00509-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/5b6832ef48a1/cells-09-00509-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/4a3872717580/cells-09-00509-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/c130c4fc69c6/cells-09-00509-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/a776f6064df8/cells-09-00509-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/1e9cbcdd7760/cells-09-00509-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/c359030a305e/cells-09-00509-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/9c6e581c33a7/cells-09-00509-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/e7a0f8561d9f/cells-09-00509-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/4e7fa7c08d87/cells-09-00509-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/5b6832ef48a1/cells-09-00509-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80f6/7072849/4a3872717580/cells-09-00509-g009.jpg

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Nonviral Transfection With Brachyury Reprograms Human Intervertebral Disc Cells to a Pro-Anabolic Anti-Catabolic/Inflammatory Phenotype: A Proof of Concept Study.Brachyury 基因非病毒转染可将人椎间盘细胞重编程为促合成代谢、抗分解代谢/抗炎表型：概念验证研究。
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