State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, Hubei Province, China.
Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, Hubei Province, China.
PLoS Genet. 2024 Oct 22;20(10):e1011319. doi: 10.1371/journal.pgen.1011319. eCollection 2024 Oct.
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.
成骨细胞是负责骨形成和维持骨骼完整性的关键细胞，来源于多种祖细胞。然而，这些多能祖细胞向成骨细胞分化的机制仍知之甚少。为了解决这一知识空白，我们开发了一个全面的框架，从多个尺度研究成骨细胞分化，包括细胞、基因和基因模块。我们构建了一个专注于分化的参考图谱，其中包含了各种成骨前体细胞，并提供了一个七级细胞分类法。为了重建分化过程，我们开发了一种模型，用于识别不同成骨前体细胞中参与分化的转录因子和途径。我们认识到年龄和组织类型等协变量可能会影响分化，因此创建了一种算法，用于检测整个分化过程中差异表达的基因。此外，我们还实施了方法来识别多个样本中保守的拟时基因模块。总的来说，我们的框架系统地解决了从不同来源观察到的成骨细胞分化中的异质性问题，为骨形成的复杂性提供了新的见解，并成为理解成骨作用的有价值资源。
