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整合发育阶段和成年阶段的小鼠四肢骨骼单细胞图谱。

A single-cell atlas of the murine limb skeleton integrating the developmental and adult stages.

作者信息

Herpelinck Tim, Ory Liesbeth, Verbraeken Tom, Nasello Gabriele, Barzegari Mojtaba, Bolander Johanna, Luyten Frank P, Tylzanowski Przemko, Geris Liesbet

机构信息

Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium.

Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium.

出版信息

Sci Rep. 2025 Jul 2;15(1):22514. doi: 10.1038/s41598-025-05277-6.

DOI:10.1038/s41598-025-05277-6
PMID:40596066
Abstract

The recent growth of single-cell transcriptomics has made single-cell RNA sequencing (scRNA-seq) into a near-routine technique. Breakthroughs in scalability have led to the creation of organism-wide transcriptomic datasets, aiming to comprehensively profile the cell types and states within an organism throughout its lifecycle. However, the skeleton remains an underrepresented organ system in organism-wide atlases. Given the skeleton's critical role as the central framework of the vertebrate body, its function in housing the hematopoietic niche, and its involvement in metabolic and homeostatic processes, its underrepresentation presents a significant gap in current reference atlas projects. To address this issue, we integrated ten separate murine, publicly available scRNA-seq datasets, which include limb skeletal cells and their developmental precursors, resulting in an atlas of 133,332 cells. This limb skeletal cell atlas describes cells within the mesenchymal lineage, focusing on the process from limb induction to adult bone formation, and encompasses 39 well-characterized cell types and states. By expanding the repertoire of time points and cell types within a single dataset, we enable more complete analyses of cell-cell communication or in silico perturbation studies. Together, these efforts present a valuable resource for researchers in skeletal biology, metabolism, and regenerative medicine, filling an important gap in current atlas mapping projects.

摘要

近年来,单细胞转录组学的发展使单细胞RNA测序(scRNA-seq)成为一种近乎常规的技术。在可扩展性方面的突破促使了全生物体转录组数据集的创建,旨在全面描绘生物体在其整个生命周期内的细胞类型和状态。然而,在全生物体图谱中,骨骼仍然是一个代表性不足的器官系统。鉴于骨骼作为脊椎动物身体的中央框架所起的关键作用、其在容纳造血微环境中的功能以及其参与代谢和稳态过程,其代表性不足在当前的参考图谱项目中构成了一个重大缺口。为了解决这个问题,我们整合了十个独立的、公开可用的小鼠scRNA-seq数据集,这些数据集包括肢体骨骼细胞及其发育前体,从而生成了一个包含133,332个细胞的图谱。这个肢体骨骼细胞图谱描述了间充质谱系中的细胞,重点关注从肢体诱导到成年骨形成的过程,涵盖了39种特征明确的细胞类型和状态。通过在单个数据集中扩展时间点和细胞类型的范围,我们能够对细胞间通讯或计算机模拟扰动研究进行更全面的分析。这些努力共同为骨骼生物学、代谢和再生医学领域的研究人员提供了宝贵的资源,填补了当前图谱绘制项目中的一个重要空白。

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