机构:[1]Center for Biomedical Digital Science, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China[2]University of Chinese Academy of Sciences, Beijing, China[3]Guangzhou National Laboratory, Guangzhou, China[4]State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China[5]Research Unit of Ocular Development and Regeneration, Chinese Academy of Medical Sciences, Beijing, China[6]Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China[7]GuangDong Engineering Technology Research Center of Biological Targeting Diagnosis, Therapy and Rehabilitation, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China[8]Guangdong Engineering Research Center of Early Clinical Trials of Biotechnology Drugs, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China[9]Bioland Laboratory, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China[10]Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong SAR, China
The transcriptomic profiling of scleral fibroblasts remains largely unexplored. To elucidate their heterogeneity, we performed single-cell RNA sequencing (scRNA-seq) on primary infant scleral fibroblasts.Primary scleral fibroblasts, cultured at passage 2 from the anterior, equatorial, and posterior regions of infant sclera (3 months to 2 years of age) were subjected to scRNA-seq using the 10x Genomics platform. In-depth analysis revealed distinct transcriptomic profiles between anterior and posterior scleral fibroblasts, including differential expression of dopamine (DA) receptors, which was subsequently validated both in vitro and in situ. Furthermore, the regulatory role of DA in scleral remodeling was assessed using an in vitro collagen gel contraction assay, and the involvement of DA receptor activity and expression in this process was further explored through pharmacological manipulation and gene silencing approaches.Infant scleral fibroblasts have anterior and posterior subpopulations, each exhibiting distinct transcriptomic profiles. Anterior scleral fibroblasts show increased expression of D1-like receptors, but posterior scleral fibroblasts exhibit elevated expression of D2-like receptors. D1-like receptor activity enhances the inhibitory effect of DA on scleral remodeling in anterior sclera, whereas D2-like receptor activity, particularly that of DRD2 in the posterior sclera, counteracts this effect. Gene silencing of DRD4 significantly enhances DA-mediated inhibition of scleral remodeling in the posterior sclera.To our knowledge, this study presents the first comprehensive transcriptomic profiling of infant scleral fibroblasts, revealing their heterogeneity. The investigation of the regulatory role of DA receptor activity and expression in DA-mediated inhibition of scleral fibroblast contraction provides new insights into how DA signaling modulates scleral remodeling.
基金:
Supported by grants from the Science and Technology Projects
in Guangzhou (202102080156, 2025A03J3233), Guangzhou
Municipal Science and Technology Bureau; the Open Research
Program of CAS Key Laboratory of Regenerative Biology,
Guangdong Provincial Key Laboratory of Stem Cell and Regenerative
Medicine, Guangzhou Institutes of Biomedicine and
Health, Chinese Academy of Sciences (KLRB202113); the
National Natural Science Foundation of China (32200461,
32370856, 82471386); CAMS Innovation Fund for Medical
Sciences (2019-I2M-5-005), the State Key Laboratory of Ophthalmology,
Zhongshan Ophthalmic Center, Sun Yat-sen University;
Key Laboratory of Guangdong Higher Education Institutes
(2021KSYS009); the Research Funds from Health@InnoHK
Program launched by Innovation Technology Commission of
the Hong Kong SAR, P. R. China; and the Major Project of
Guangzhou National Laboratory (GZNL2024A03012).
语种:
外文
PubmedID:
中科院(CAS)分区:
出版当年[2025]版:
大类|2 区医学
小类|2 区眼科学
最新[2025]版:
大类|2 区医学
小类|2 区眼科学
第一作者:
第一作者机构:[1]Center for Biomedical Digital Science, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China[2]University of Chinese Academy of Sciences, Beijing, China
共同第一作者:
通讯作者:
推荐引用方式(GB/T 7714):
Guan Jiali,Hong Guangliang,Liu Zhong,et al.Distinct Transcriptomic Profiles of Cultured Anterior and Posterior Populations of Human Infant Scleral Fibroblasts: Including Dopamine Receptors[J].Investigative Ophthalmology & Visual Science.2025,66(5):29.doi:10.1167/iovs.66.5.29.
APA:
Guan Jiali,Hong Guangliang,Liu Zhong,Zheng Yingfeng,He Jiangping...&Li He.(2025).Distinct Transcriptomic Profiles of Cultured Anterior and Posterior Populations of Human Infant Scleral Fibroblasts: Including Dopamine Receptors.Investigative Ophthalmology & Visual Science,66,(5)
MLA:
Guan Jiali,et al."Distinct Transcriptomic Profiles of Cultured Anterior and Posterior Populations of Human Infant Scleral Fibroblasts: Including Dopamine Receptors".Investigative Ophthalmology & Visual Science 66..5(2025):29