Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, 410081 Changsha, Hunan, China.
Tulane Center of Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Front Biosci (Landmark Ed). 2022 Oct 31;27(10):295. doi: 10.31083/j.fbl2710295.
Recently, single-cell RNA sequencing (scRNA-seq) technology was increasingly used to study transcriptomics at a single-cell resolution, scRNA-seq analysis was complicated by the "dropout", where the data only captures a small fraction of the transcriptome. This phenomenon can lead to the fact that the actual expressed transcript may not be detected. We previously performed osteoblast subtypes classification and dissection on freshly isolated human osteoblasts.
Here, we used the scImpute method to impute the missing values of dropout genes from a scRNA-seq dataset generated on freshly isolated human osteoblasts.
Based on the imputed gene expression patterns, we discovered three new osteoblast subtypes. Specifically, these newfound osteoblast subtypes are osteoblast progenitors, and two undetermined osteoblasts. Osteoblast progenitors showed significantly high expression of proliferation related genes ( and ). Analysis of each subtype showed that in addition to bone formation, these undetermined osteoblasts may involve osteoclast and adipocyte differentiation and have the potential function of regulate immune activation.
Our findings provided a new perspective for studying the osteoblast heterogeneity and potential biological functions of these freshly isolated human osteoblasts at the single-cell level, which provides further insight into osteoblasts subtypes under various (pathological) physiological conditions.
最近，单细胞 RNA 测序（scRNA-seq）技术越来越多地用于研究单细胞分辨率的转录组学，scRNA-seq 分析受到“缺失”的影响，数据仅捕获了转录组的一小部分。这种现象可能导致实际表达的转录本无法被检测到。我们之前对新鲜分离的人成骨细胞进行了成骨细胞亚型分类和剖析。
在这里，我们使用 scImpute 方法从新鲜分离的人成骨细胞生成的 scRNA-seq 数据集估算缺失基因的缺失值。
基于估算的基因表达模式，我们发现了三种新的成骨细胞亚型。具体而言，这些新发现的成骨细胞亚型是成骨细胞祖细胞和两种未确定的成骨细胞。成骨细胞祖细胞表现出与增殖相关的基因的显著高表达（和）。对每种亚型的分析表明，除了骨形成外，这些未确定的成骨细胞可能涉及破骨细胞和脂肪细胞分化，并具有调节免疫激活的潜在功能。
我们的研究结果为在单细胞水平上研究成骨细胞异质性和这些新鲜分离的人成骨细胞的潜在生物学功能提供了新的视角，这为各种（病理）生理条件下的成骨细胞亚型提供了更深入的了解。
