研究从人类诱导多能干细胞分化出的胰腺β样细胞亚群中转录调节因子的主题活动。

IF 3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Molecular omics Pub Date : 2024-11-04 DOI:10.1039/D4MO00082J
Eric Leclerc, Mikhail Pachkov, Lisa Morisseau, Fumiya Tokito, Cecile Legallais, Rachid Jellali, Masaki Nishikawa, Amar Abderrahmani and Yasuyuki Sakai
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引用次数: 0

摘要

胰腺β细胞由不同的亚型组成,它们在控制胰岛素分泌方面发挥着关键作用,从而控制葡萄糖稳态。将人类诱导多能干细胞(hiPSCs)体外分化成三维球形,可产生β细胞亚型,从而形成类似小岛的结构。利用这一尖端细胞模型,研究的目的是破译突显β细胞亚型的信号特征,重点是寻找重要转录调节因子(TRs)基团的活性。这项研究利用了之前单细胞测序分析中的数据,并将其引入转录调节因子主题词活性响应分析集成系统(ISMARA)。我们提取了在β细胞亚群和双激素样β细胞中激活的重要TRs矩阵。根据这些 TRs 及其靶标,我们为主要细胞亚群构建了特定的调控网络。我们的数据证实了β细胞亚型系的转录组异质性,并提出了胰腺发育过程中β细胞亚型分化的机制。我们相信,我们的发现有助于理解影响β细胞亚型平衡的机制,从而导致2型糖尿病患者胰岛素分泌受损。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Investigation of the motif activity of transcription regulators in pancreatic β-like cell subpopulations differentiated from human induced pluripotent stem cells†

Investigation of the motif activity of transcription regulators in pancreatic β-like cell subpopulations differentiated from human induced pluripotent stem cells†

Pancreatic β-cells are composed of different subtypes that play a key role in the control of insulin secretion and thereby control glucose homeostasis. In vitro differentiation of human induced pluripotent stem cells (hiPSCs) into 3D spheroids leads to the generation of β-cell subtypes and thus to the development of islet-like structures. Using this cutting-edge cell model, the aim of the study was to decipher the signaling signature that underlines β-cell subtypes, with a focus on the search for the activity of motifs of important transcription regulators (TRs). The investigation was performed using data from previous single-cell sequencing analysis introduced into the integrated system for motif activity response analysis (ISMARA) of transcription regulators. We extracted the matrix of important TRs activated in the β-cell subpopulation and bi-hormonal-like β-cells. Based on these TRs and their targets, we built specific regulatory networks for main cell subpopulations. Our data confirmed the transcriptomic heterogeneity of the β-cell subtype lineage and suggested a mechanism that could account for the differentiation of β-cell subtypes during pancreas development. We do believe that our findings could be instrumental for understanding the mechanisms that affect the balance of β-cell subtypes, leading to impaired insulin secretion in type 2 diabetes.

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来源期刊
Molecular omics
Molecular omics Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
5.40
自引率
3.40%
发文量
91
期刊介绍: Molecular Omics publishes high-quality research from across the -omics sciences. Topics include, but are not limited to: -omics studies to gain mechanistic insight into biological processes – for example, determining the mode of action of a drug or the basis of a particular phenotype, such as drought tolerance -omics studies for clinical applications with validation, such as finding biomarkers for diagnostics or potential new drug targets -omics studies looking at the sub-cellular make-up of cells – for example, the subcellular localisation of certain proteins or post-translational modifications or new imaging techniques -studies presenting new methods and tools to support omics studies, including new spectroscopic/chromatographic techniques, chip-based/array technologies and new classification/data analysis techniques. New methods should be proven and demonstrate an advance in the field. Molecular Omics only accepts articles of high importance and interest that provide significant new insight into important chemical or biological problems. This could be fundamental research that significantly increases understanding or research that demonstrates clear functional benefits. Papers reporting new results that could be routinely predicted, do not show a significant improvement over known research, or are of interest only to the specialist in the area are not suitable for publication in Molecular Omics.
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