Effects of macrophage-conditioned medium on sika deer (Cervus nippon) antler stem cells
Zhen Wang A B , Datao Wang C , Tao Qin C , Hengxing Ba C , Guanning Wei C , Yong Li D , Wei Yu B E and Chunyi Li A C EA Changchun Sci-Tech University, 1699 Donghua Street, Changchun 130600, China.
B College of Life Sciences and Medicine, Zhejiang Sci-Tech University, 928 No. 2 Street, Xiasha Higher Education Park, Hangzhou 310018, China.
C Institute of Special Wild Economic Animals and Plants, Chinese Academy of Agricultural Sciences, 4899 Juye Street, Changchun 130112, China.
D Tangshan Eighth Hospital, 16 West Kiln Road, Tangshan 063000, China.
E Corresponding author. Email: yuwei@zstu.edu.cn; lichunyi1959@163.com
Animal Production Science 60(10) 1326-1333 https://doi.org/10.1071/AN19553
Submitted: 25 September 2019 Accepted: 7 December 2019 Published: 24 April 2020
Abstract
Context: Immune system has been claimed as the ‘main switch’ of tissue or organ regeneration. Among immune cells, macrophages stand out as important modulators in mutiple regeneration models, such as planarian, axolotl, mammalian hair and liver. As a unique model for mammals, deer antler is considered to ideal for studying complete mammalian organ regeneration. Studies have found that antler regeneration is a stem cell-based process and antler stem cells locate in the pedicle periosteum (PP). Although the regulatory roles of the immune system in other regeneration models have been extensively studied, they remain unstudied in antler regeneration.
Aims: To explore the possible role of macrophages in the PP cells (PPCs).
Methods: We treated PPCs with a macrophage-conditioned medium (MCM) and detected effects of MCM on proliferation, migration and apoptosis of the PPCs, and identified differentially expressed genes by using the RNA-seq technique.
Key results: We found that MCM enhanced proliferation rate and migration rate significantly and stimulated apoptosis of the PPCs. Using the RNA-seq technique, we identified 112 differentially expressed genes in the PPCs (38 downregulated and 74 upregulated) after the MCM treatment. Furthermore, gene-ontology annotation analyses showed that the upregulated genes were mainly involved in cell adhesion, chemotaxis, wound healing, growth factor-stimulated responses, and bone formation, and the downregulated genes were involved in regulation of biosynthesis.
Conclusions: MCM had a great influence on the antler stem cells, and macrophages might regulate antler regeneration through altering the microenvironment and gene-expression profiles of the PPCs.
Implications: We believe that the results of the present study would facilitate the discovery of the roles of immune system in antler stem cells and, thus, mammalian organ regeneration in general.
Additional keywords: antler regeneration, differentially expressed genes, macrophages, RNA-seq.
References
Anders S, Huber W (2010) Differential expression analysis for sequence count data. Genome Biology 11, R106| Differential expression analysis for sequence count data.Crossref | GoogleScholarGoogle Scholar | 20979621PubMed |
Araujo FM, Meola J, Rosa ESJC, Paz CCP, Ferriani RA, Nogueira AA (2017) Increased expression of ID2, PRELP and SMOC2 genes in patients with endometriosis. Brazilian Journal of Medical and Biological Research 50, e5782
| Increased expression of ID2, PRELP and SMOC2 genes in patients with endometriosis.Crossref | GoogleScholarGoogle Scholar | 28678915PubMed |
Ba H, Wang D, Li C (2016) MicroRNA profiling of antler stem cells in potentiated and dormant states and their potential roles in antler regeneration. Molecular Genetics and Genomics 291, 943–955.
Chen W, Ye L, Wen D, Chen F (2019) MiR-490-5p inhibits hepatocellular carcinoma cell proliferation, migration and invasion by directly regulating ROBO1. Pathology Oncology Research 25, 1–9.
| MiR-490-5p inhibits hepatocellular carcinoma cell proliferation, migration and invasion by directly regulating ROBO1.Crossref | GoogleScholarGoogle Scholar | 28924964PubMed |
Godwin JW, Pinto AR, Rosenthal NA (2013) Macrophages are required for adult salamander limb regeneration. Proceedings of the National Academy of Sciences, USA 110, 9415–9420.
| Macrophages are required for adult salamander limb regeneration.Crossref | GoogleScholarGoogle Scholar |
Hodgkinson CP, Gomez JA, Payne AJ, Zhang L, Wang X, Dal-Pra S, Pratt RE, Dzau VJ (2014) Abi3bp regulates cardiac progenitor cell proliferation and differentiation. Circulation Research 115, 1007–1016.
| Abi3bp regulates cardiac progenitor cell proliferation and differentiation.Crossref | GoogleScholarGoogle Scholar | 25296984PubMed |
Hwang JR, Cho YJ, Lee Y, Park Y, Han HD, Ahn HJ, Lee JH, Lee JW (2016) The C-terminus of IGFBP-5 suppresses tumor growth by inhibiting angiogenesis. Scientific Reports 6, 39334
| The C-terminus of IGFBP-5 suppresses tumor growth by inhibiting angiogenesis.Crossref | GoogleScholarGoogle Scholar | 28008951PubMed |
Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nature Immunology 11, 373–384.
| The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors.Crossref | GoogleScholarGoogle Scholar | 20404851PubMed |
Li C, Suttie JM (2003) Tissue collection methods for antler research. European Journal of Morphology 41, 23–30.
| Tissue collection methods for antler research.Crossref | GoogleScholarGoogle Scholar | 15121545PubMed |
Li C, Mackintosh CG, Martin SK, Clark DE (2007) Identification of key tissue type for antler regeneration through pedicle periosteum deletion. Cell and Tissue Research 328, 65–75.
| Identification of key tissue type for antler regeneration through pedicle periosteum deletion.Crossref | GoogleScholarGoogle Scholar | 17120051PubMed |
Li C, Yang F, Sheppard A (2009) Adult stem cells and mammalian epimorphic regeneration: insights from studying annual renewal of deer antlers. Current Stem Cell Research & Therapy 4, 237–251.
| Adult stem cells and mammalian epimorphic regeneration: insights from studying annual renewal of deer antlers.Crossref | GoogleScholarGoogle Scholar |
Li C, Harper A, Puddick J, Wang W, McMahon C (2012) Proteomes and signalling pathways of antler stem cells. PLoS One 7, e30026
| Proteomes and signalling pathways of antler stem cells.Crossref | GoogleScholarGoogle Scholar | 23285183PubMed |
Mathiyalagan P, Liang Y, Kim D, Misener S, Thorne T, Kamide CE, Klyachko E, Losordo DW, Hajjar RJ, Sahoo S (2017) Angiogenic mechanisms of human CD34(+) stem cell exosomes in the repair of ischemic hindlimb. Circulation Research 120, 1466–1476.
| Angiogenic mechanisms of human CD34(+) stem cell exosomes in the repair of ischemic hindlimb.Crossref | GoogleScholarGoogle Scholar | 28298297PubMed |
Simkin J, Sammarco MC, Marrero L, Dawson LA, Yan M, Tucker C, Cammack A, Muneoka K (2017) Macrophages are required to coordinate mouse digit tip regeneration. Development 144, 3907–3916.
| Macrophages are required to coordinate mouse digit tip regeneration.Crossref | GoogleScholarGoogle Scholar | 28935712PubMed |
Song YJ, Li G, He JH, Guo Y, Yang L (2015) Bioinformatics-based identification of microRNA-regulated and rheumatoid arthritis-associated genes. PLoS One 10, e0137551
| Bioinformatics-based identification of microRNA-regulated and rheumatoid arthritis-associated genes.Crossref | GoogleScholarGoogle Scholar | 26540392PubMed |
Wang W, Mou S, Wang L, Zhang M, Shao X, Fang W, Lu R, Qi C, Fan Z, Cao Q, Wang Q, Fang Y, Ni Z (2015) Up-regulation of serum miR-130b-3p level is associated with renal damage in early lupus nephritis. Scientific Reports 5, 12644
| Up-regulation of serum miR-130b-3p level is associated with renal damage in early lupus nephritis.Crossref | GoogleScholarGoogle Scholar | 26316103PubMed |
Wang D, Berg D, Ba H, Sun H, Wang Z, Li C (2019) Deer antler stem cells are a novel type of cells that sustain full regeneration of a mammalian organ – deer antler. Cell Death & Disease 10, 443
| Deer antler stem cells are a novel type of cells that sustain full regeneration of a mammalian organ – deer antler.Crossref | GoogleScholarGoogle Scholar |
Yang H, Han Y, Wu L, Wu C (2017) Diagnostic and prognostic value of serum interleukin-16 in patients with gastric cancer. Molecular Medicine Reports 16, 9143–9148.
| Diagnostic and prognostic value of serum interleukin-16 in patients with gastric cancer.Crossref | GoogleScholarGoogle Scholar | 28990054PubMed |
Yu L, Yu L, Pham Q, Wang TTY (2018) Transcriptional and translational-uncoupling in regulation of the CXCL12 and its receptors CXCR4, 7 in THP-1 monocytes and macrophages. Immunity, Inflammation and Disease 6, 106–116.
| Transcriptional and translational-uncoupling in regulation of the CXCL12 and its receptors CXCR4, 7 in THP-1 monocytes and macrophages.Crossref | GoogleScholarGoogle Scholar | 29105376PubMed |