Secretome Analysis of Testicular Peritubular Cells: A Window into the Human Testicular Microenvironment and the Spermatogonial Stem Cell Niche in Man

被引：49

作者：

Flenkenthaler, Florian ^{[1
]}

Windschuettl, Stefanie ^{[2
]}

Froehlich, Thomas ^{[1
]}

Schwarzer, J. Ullrich ^{[3
]}

Mayerhofer, Artur ^{[2
]}

Arnold, Georg J. ^{[1
]}

机构：

[1] Univ Munich, Gene Ctr, Lab Funct Genome Anal LAFUGA, Munich, Germany

[2] Univ Munich, Fac Med, Munich, Germany

[3] Androl Ctr Munchen, Munich, Germany

来源：

JOURNAL OF PROTEOME RESEARCH | 2014年 / 13卷 / 03期

关键词：

human testis; mass spectrometry; peritubular cells; secretome; spermatogenesis; stem cell niche; UNDIFFERENTIATED SPERMATOGONIA; EXTRACELLULAR-MATRIX; SERTOLI-CELLS; MYOID CELLS; NEUROTROPHIC FACTOR; ADHESION MOLECULES; STATISTICAL-MODEL; GENE ONTOLOGY; HUMAN TESTIS; PROTEIN;

D O I：

10.1021/pr400769z

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Spermatogonial stem cells (SSCs) are vital for lifelong spermatogenesis in man. In their niches, a special growth factor milieu and structural support by surrounding cells are thought to ensure their maintenance. In man, the cells of the wall of seminiferous tubules, human testicular peritubular cells (HTPCs), are considered to contribute to this microenvironment and the overall testicular microenvironment via secreted proteins. Therefore, the secretome of cultured HTPCs from five individual men was analyzed by LC-MS/MS. Quantification and comparison to the proteome of HTPC lysates revealed 263 out of 660 identified secretome proteins to be at least 5-fold enriched in the culture media. To obtain additional evidence for secretion, signal peptide and gene ontology (GO) enrichment analyses were applied. The latter revealed besides extracellular matrix (ECM) components a significant over-representation of chemokines and growth factors acting in signaling pathways that appear critical for SSC maintenance. Immunohistochemistry, performed with human testicular sections, depicted expression of selected proteins in vivo. The significant enrichment of proteins related to cell adhesion and migration may indicate their involvement in SSC regulation. Our data strongly support the hypothesis of a crucial role of HTPCs in the composition of SSC niches in man.

引用

页码：1259 / 1269

页数：11

共 69 条

[1] Decorin is a part of the ovarian extracellular matrix in primates and may act as a signaling molecule [J].

Adam, M. ;

Saller, S. ;

Stroebl, S. ;

Hennebold, J. D. ;

Dissen, G. A. ;

Ojeda, S. R. ;

Stouffer, R. L. ;

Berg, D. ;

Berg, U. ;

Mayerhofer, A. .

HUMAN REPRODUCTION, 2012, 27 (11) :3249-3258

[2] High levels of the extracellular matrix proteoglycan decorin are associated with inhibition of testicular function [J].

Adam, M. ;

Urbanski, H. F. ;

Garyfallou, V. T. ;

Welsch, U. ;

Koehn, F. M. ;

Schwarzer, J. Ullrich ;

Strauss, L. ;

Poutanen, M. ;

Mayerhofer, A. .

INTERNATIONAL JOURNAL OF ANDROLOGY, 2012, 35 (04) :550-561

[3] Mast cell tryptase stimulates production of decorin by human testicular peritubular cells: possible role of decorin in male infertility by interfering with growth factor signaling [J].

Adam, M. ;

Schwarzer, J. U. ;

Koehn, F. M. ;

Strauss, L. ;

Poutanen, M. ;

Mayerhofer, A. .

HUMAN REPRODUCTION, 2011, 26 (10) :2613-2625

[4] Isolation and cultivation of human testicular peritubular cells: A new model for the investigation of fibrotic processes in the human testis and male infertility [J].

Albrecht, M ;

Raemsch, R ;

Koehn, FM ;

Schwarzer, JU ;

Mayerhofer, A .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2006, 91 (05) :1956-1960

[5] Insights into the nature of human testicular peritubular cells [J].

Albrecht, Martin .

ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, 2009, 191 (06) :532-540

[6] Quantitation of proteins using a dye-metal-based colorimetric protein assay [J].

Antharavally, Babu S. ;

Mallia, Krishna A. ;

Rangaraj, Priya ;

Haney, Paul ;

Bell, Peter A. .

ANALYTICAL BIOCHEMISTRY, 2009, 385 (02) :342-345

[7] Gene Ontology: tool for the unification of biology [J].

Ashburner, M ;

Ball, CA ;

Blake, JA ;

Botstein, D ;

Butler, H ;

Cherry, JM ;

Davis, AP ;

Dolinski, K ;

Dwight, SS ;

Eppig, JT ;

Harris, MA ;

Hill, DP ;

Issel-Tarver, L ;

Kasarskis, A ;

Lewis, S ;

Matese, JC ;

Richardson, JE ;

Ringwald, M ;

Rubin, GM ;

Sherlock, G .

NATURE GENETICS, 2000, 25 (01) :25-29

[8] Activins and inhibins in mammalian testis development: New models, new insights [J].

Barakat, B. ;

Itman, C. ;

Mendis, S. H. ;

Loveland, K. L. .

MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2012, 359 (1-2) :66-77

[9] The pattern recognition receptor PTX3 is recruited at the synapse between dying and dendritic cells, and edits the cross-presentation of self, viral, and tumor antigens [J].

Baruah, P ;

Propato, A ;

Dumitriu, IE ;

Rovere-Querini, P ;

Russo, V ;

Fontana, R ;

Accapezzato, D ;

Peri, G ;

Mantovani, A ;

Barnaba, V ;

Manfredi, AA .

BLOOD, 2006, 107 (01) :151-158

[10] ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks [J].

Bindea, Gabriela ;

Mlecnik, Bernhard ;

Hackl, Hubert ;

Charoentong, Pornpimol ;

Tosolini, Marie ;

Kirilovsky, Amos ;

Fridman, Wolf-Herman ;

Pages, Franck ;

Trajanoski, Zlatko ;

Galon, Jerome .

BIOINFORMATICS, 2009, 25 (08) :1091-1093

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