Deciphering postnatal limb development at single-cell resolution

Manman Gao; Xizhe Liu; Peng Guo; Jianmin Wang; Junhong Li; Wentao Wang; Martin J Stoddart; Sibylle Grad; Zhen Li; Huachuan Wu; Baoliang Li; Zhongyuan He; Guangqian Zhou; Shaoyu Liu; Weimin Zhu; Dafu Chen; Xuenong Zou; Zhiyu Zhou

doi:10.1016/j.isci.2022.105808

Deciphering postnatal limb development at single-cell resolution

iScience. 2022 Dec 13;26(1):105808. doi: 10.1016/j.isci.2022.105808. eCollection 2023 Jan 20.

Authors

Manman Gao^{1

2

3

4}, Xizhe Liu³, Peng Guo^{1

3}, Jianmin Wang^{1

3}, Junhong Li^{1

3}, Wentao Wang^{1

3}, Martin J Stoddart⁵, Sibylle Grad⁵, Zhen Li⁵, Huachuan Wu^{1

3}, Baoliang Li^{1

3}, Zhongyuan He^{1

3}, Guangqian Zhou⁴, Shaoyu Liu^{1

3}, Weimin Zhu^{2

4}, Dafu Chen⁶, Xuenong Zou³, Zhiyu Zhou^{1

3}

Affiliations

¹ Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.
² Department of Sport Medicine, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, China.
³ Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
⁴ Shenzhen Key Laboratory of Anti-aging and Regenerative Medicine, Department of Medical Cell Biology and Genetics, Health Sciences Center, Shenzhen University, Shenzhen 518071, China.
⁵ AO Research Institute Davos, Davos 7270, Switzerland.
⁶ Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical Materials, Beijing Research Institute of Orthopaedics and Traumatology, Beijing JiShuiTan Hospital, Beijing 100035, China.

Abstract

The early postnatal limb developmental progression bridges embryonic and mature stages and mirrors the pathological remodeling of articular cartilage. However, compared with multitudinous research on embryonic limb development, the early postnatal stage seems relatively unnoticed. Here, a systematic work to portray the postnatal limb developmental landscape was carried out by characterization of 19,952 single cells from murine hindlimbs at 4 postnatal stages using single-cell RNA sequencing technique. By delineation of cell heterogeneity, the candidate progenitor sub-clusters marked by Cd34 and Ly6e were discovered in articular cartilage and enthesis, and three cellular developmental branches marked by Col10a1, Spp1, and Tnni2 were reflected in growth plate. The representative transcriptomes and developmental patterns were intensively explored, and the key regulation mechanisms as well as evolvement in osteoarthritis were discussed. Above all, these results expand horizons of postnatal limb developmental biology and reach the interconnections between limb development, remodeling, and regeneration.

Keywords: Biological sciences; Omics; Transcriptomics.