Trajectory-centric framework TrajAtlas reveals multi-scale differentiation heterogeneity among cells, genes, and gene modules in osteogenesis.

IF 4 2区 生物学 Q1 GENETICS & HEREDITY
PLoS Genetics Pub Date : 2024-10-22 eCollection Date: 2024-10-01 DOI:10.1371/journal.pgen.1011319
Litian Han, Yaoting Ji, Yiqian Yu, Yueqi Ni, Hao Zeng, Xiaoxin Zhang, Huan Liu, Yufeng Zhang
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引用次数: 0

Abstract

Osteoblasts, the key cells responsible for bone formation and the maintenance of skeletal integrity, originate from a diverse array of progenitor cells. However, the mechanisms underlying osteoblast differentiation from these multiple osteoprogenitors remain poorly understood. To address this knowledge gap, we developed a comprehensive framework to investigate osteoblast differentiation at multiple scales, encompassing cells, genes, and gene modules. We constructed a reference atlas focused on differentiation, which incorporates various osteoprogenitors and provides a seven-level cellular taxonomy. To reconstruct the differentiation process, we developed a model that identifies the transcription factors and pathways involved in differentiation from different osteoprogenitors. Acknowledging that covariates such as age and tissue type can influence differentiation, we created an algorithm to detect differentially expressed genes throughout the differentiation process. Additionally, we implemented methods to identify conserved pseudotemporal gene modules across multiple samples. Overall, our framework systematically addresses the heterogeneity observed during osteoblast differentiation from diverse sources, offering novel insights into the complexities of bone formation and serving as a valuable resource for understanding osteogenesis.

以轨迹为中心的框架 TrajAtlas 揭示了成骨过程中细胞、基因和基因模块之间的多尺度分化异质性。
成骨细胞是负责骨骼形成和维持骨骼完整性的关键细胞,它起源于多种多样的祖细胞。然而,人们对成骨细胞从这些多种成骨祖细胞分化而来的机制仍然知之甚少。为了填补这一知识空白,我们开发了一个综合框架,从细胞、基因和基因模块等多个尺度研究成骨细胞分化。我们构建了一个以分化为重点的参考图谱,其中包含各种造骨细胞,并提供了七级细胞分类法。为了重建分化过程,我们建立了一个模型,从不同的成骨细胞中找出参与分化的转录因子和通路。考虑到年龄和组织类型等协变量会影响分化,我们创建了一种算法来检测整个分化过程中的差异表达基因。此外,我们还采用了一些方法来识别多个样本中的保守伪时相基因模块。总之,我们的框架系统地解决了成骨细胞分化过程中观察到的不同来源的异质性问题,为了解骨形成的复杂性提供了新的见解,是了解成骨过程的宝贵资源。
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来源期刊
PLoS Genetics
PLoS Genetics GENETICS & HEREDITY-
自引率
2.20%
发文量
438
期刊介绍: PLOS Genetics is run by an international Editorial Board, headed by the Editors-in-Chief, Greg Barsh (HudsonAlpha Institute of Biotechnology, and Stanford University School of Medicine) and Greg Copenhaver (The University of North Carolina at Chapel Hill). Articles published in PLOS Genetics are archived in PubMed Central and cited in PubMed.
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