title: Single-cell analysis reveals a nestin+tendon stem/progenitor cell population with strong tenogenic potentiality.
abstract: The repair of injured tendons remains a formidable clinical challenge because of our limited understanding of tendon stem cells and the regulation of tenogenesis. With single-cell analysis to characterize the gene expression profiles of individual cells isolated from tendon tissue, a subpopulation of nestin+tendon stem/progenitor cells (TSPCs) was identified within the tendon cell population. Using Gene Expression Omnibus datasets and immunofluorescence assays, we found that nestin expression was activated at specific stages of tendon development. Moreover, isolated nestin+TSPCs exhibited superior tenogenic capacity compared to nestin-TSPCs. Knockdown of nestin expression in TSPCs suppressed their clonogenic capacity and reduced their tenogenic potential significantly both in vitro and in vivo. Hence, these findings provide new insights into the identification of subpopulations of TSPCs and illustrate the crucial roles of nestin in TSPC fate decisions and phenotype maintenance, which may assist in future therapeutic strategies to treat tendon disease.
authors.affiliation: Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, China.; China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jia-Jie
authors.initials: JJ
authors.lastname: Hu
authors.affiliation: Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Long
authors.identifier: 0000-0003-2597-4859
authors.initials: L
authors.lastname: Yang
authors.affiliation: Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Ze-Feng
authors.identifier: 0000-0002-2532-5675
authors.initials: ZF
authors.lastname: Zheng
authors.affiliation: Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Cheng-Rui
authors.initials: CR
authors.lastname: An
authors.affiliation: Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Bing-Bing
authors.initials: BB
authors.lastname: Wu
authors.affiliation: Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Can
authors.initials: C
authors.lastname: Zhang
authors.affiliation: China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou, China.; Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Wei-Liang
authors.identifier: 0000-0001-8131-325X
authors.initials: WL
authors.lastname: Shen
authors.affiliation: Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Liu
authors.affiliation: Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Chen
authors.affiliation: Faculty of Dentistry, University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Boon Chin
authors.initials: BC
authors.lastname: Heng
authors.affiliation: Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Guo-Ji
authors.initials: GJ
authors.lastname: Guo
authors.affiliation: Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, China.; China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, China.; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, China.; China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou, China.; Department of Sports Medicine, School of Medicine, Zhejiang University, Hangzhou, China.; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Ouyang
mesh_terms: D000818:Animals; D030561:Databases, Nucleic Acid; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D064231:Nestin / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013710:Tendons / Q000166:cytology / Q000378:metabolism*
chemical_list: C577485:Nes protein, mouse; D064231:Nestin
keywords: Tendons stem/progenitor cells; nestin; single-cell gene analysis; tenogenesis