Atlas; Bioinformatics; Bone; Limb; Morphogenesis; Single-cell; Transcriptome; Animals; Mice; Gene Expression Profiling; Atlases as Topic; Single-Cell Analysis/methods; Extremities/growth & development; Bone and Bones/cytology; Bone and Bones/metabolism; Bone and Bones; Extremities; Single-Cell Analysis; Multidisciplinary
Abstract :
[en] 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.
Disciplines :
Engineering, computing & technology: Multidisciplinary, general & others
Author, co-author :
Herpelinck, Tim; Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium ; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium
Ory, Liesbeth; Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium ; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium
Verbraeken, Tom; Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium ; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium
Nasello, Gabriele; Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium ; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium
Barzegari, Mojtaba; Biomechanics Section, Department of Mechanical Engineering, KU Leuven, Leuven, Belgium
Bolander, Johanna; Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, 7 NC, USA
Luyten, Frank P; Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium ; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium
Tylzanowski, Przemko; Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium ; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium ; Department of Biomedical Sciences, Laboratory of Molecular Genetics, Medical University of Lublin, Lublin, Poland
Geris, Liesbet ; Université de Liège - ULiège > Département d'aérospatiale et mécanique > Génie biomécanique ; Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium. liesbet.geris@kuleuven.be ; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium. liesbet.geris@kuleuven.be ; Biomechanics Section, Department of Mechanical Engineering, KU Leuven, Leuven, Belgium. liesbet.geris@kuleuven.be
Language :
English
Title :
A single-cell atlas of the murine limb skeleton integrating the developmental and adult stages.
FWO - Fonds Wetenschappelijk Onderzoek Vlaanderen EU - European Union ERC - European Research Council
Funding text :
We would like to thank Inge Van Hoven for assistance and Ronny Moreas for technical support in the deployment of the web app. Research was funded by the Research Foundation Flanders (FWO Vlaanderen) T.H.: 1S80021N, G.N.: 12C5923N, MatheMorphosis: G0D3420N, and FWO-INSITE: G085018N; by the European Union\u2019s Horizon 2020 Framework Program (H2020/2014-2021) ERC INSITE (772418) and SC1-DTH ISW (101016503); by the European Union\u2019s Horizon Europe Framework Program (HEU/2022-2027) ERC INSTant CARMA (101088919), as well as by the special research fund of the KU Leuven (C24/17/077). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript. This work is part of Prometheus, the KU Leuven R&D division for skeletal tissue engineering (http://www.kuleuven.be/prometheus).
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