The Telomerase Activity of Adult Mouse Testis Resides in the Spermatogonial α6-Integrin-Positive Side Population Enriched in Germinal Stem Cells

Riou, Lydia; Bastos, Henri; Lassalle, Bruno; Coureuil, Mathieu; Testart, J; Boussin, François D.; Allemand, Isabelle; Fouchet, Pierre

doi:10.1210/en.2005-0502

Cited by 30 publications

(16 citation statements)

References 36 publications

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“…Previous studies attempting to localize telomerase expression within the germ cell lineage showed widely divergent results. A subset of the studies did find elevated expression in partially purified spermatogonia, which is consistent with our data (Ravindranath et al 1997;Kanatsu-Shinohara et al 2003;Riou et al 2005).…”

Section: The Tertsupporting

confidence: 91%

High telomerase is a hallmark of undifferentiated spermatogonia and is required for maintenance of male germline stem cells

et al. 2015

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Telomerase inactivation causes loss of the male germline in worms, fish, and mice, indicating a conserved dependence on telomere maintenance in this cell lineage. Here, using telomerase reverse transcriptase (Tert) reporter mice, we found that very high telomerase expression is a hallmark of undifferentiated spermatogonia, the mitotic population where germline stem cells reside. We exploited these high telomerase levels as a basis for purifying undifferentiated spermatogonia using fluorescence-activated cell sorting. Telomerase levels in undifferentiated spermatogonia and embryonic stem cells are comparable and much greater than in somatic progenitor compartments. Within the germline, we uncovered an unanticipated gradient of telomerase activity that also enables isolation of more mature populations. Transcriptomic comparisons of Tert High undifferentiated spermatogonia and Tert Low differentiated spermatogonia by RNA sequencing reveals marked differences in cell cycle and key molecular features of each compartment. Transplantation studies show that germline stem cell activity is confined to the Tert High cKit − population. Telomere shortening in telomerase knockout strains causes depletion of undifferentiated spermatogonia and eventual loss of all germ cells after undifferentiated spermatogonia drop below a critical threshold. These data reveal that high telomerase expression is a fundamental characteristic of germline stem cells, thus explaining the broad dependence on telomerase for germline immortality in metazoans.

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Section: The Tertsupporting

confidence: 91%

High telomerase is a hallmark of undifferentiated spermatogonia and is required for maintenance of male germline stem cells

et al. 2015

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“…It is generally accepted that only few normal cell types such as male germ-line spermatocytes and around 90% of all cancers exhibit telomerase activity [164,165]. In adult mice, telomerase was detected in a positive α6-integrin subpopulation containing spermatogonia and enriched in spermatogonial stem cells [166]. …”

Section: Hallmarking Cancermentioning

confidence: 99%

Integrins in the Spotlight of Cancer

Bianconi

Unseld

Prager

2016

IJMS

130

110

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Integrins are heterodimeric cell surface receptors that bind to different extracellular ligands depending on their composition and regulate all processes which enable multicellular life. In cancer, integrins trigger and play key roles in all the features that were once described as the Hallmarks of Cancer. In this review, we will discuss the contribution of integrins to these hallmarks, including uncontrolled and limitless proliferation, invasion of tumor cells, promotion of tumor angiogenesis and evasion of apoptosis and resistance to growth suppressors, by highlighting the latest findings. Further on, given the paramount role of integrins in cancer, we will present novel strategies for integrin inhibition that are starting to emerge, promising a hopeful future regarding cancer treatment.

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“…Today, Hoechst 33342 excluding cells are commonly referred to as side population cells. Such cells can be found in a wide variety of tissues, and the side population strategy has been useful for isolating cells with high regenerative capacity from hematopoietic (3, 5, 6), airway (7), pituitary (8), small intestine (9), and testicular (10) tissues. However, given the wide array of biological functions that ABC transporters serve, and the fact that they are sometimes induced in transporter-negative cells by substrate exposure, the caveat must be given that MDR expression does not unequivocally identify stem cells and conversely, its absence does not rule out the self-renewing capacity most characteristic of stemness.…”

Section: Introductionmentioning

confidence: 99%

Measurement of Multiple Drug Resistance Transporter Activity in Putative Cancer Stem/Progenitor Cells

Donnenberg

Meyer

Donnenberg

2009

Methods in Molecular Biology

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Summary Multiple drug resistance, mediated by the expression and activity of ABC-transporters, is a major obstacle to antineoplastic therapy. Normal tissue stem cells and their malignant counterparts share MDR transporter activity as a major mechanism of self-protection. Although MDR activity is upregulated in response to substrate chemotherapeutic agents, it is also constitutively expressed on both normal tissue stem cells and a subset of tumor cells prior to the initiation of therapy, representing a built-in obstacle to therapeutic ratio. Constitutive and induced MDR activity can be detected in cellular subsets of disaggregated tissues, using the fluorescent substrates Rhodamine 123 and Hoechst 33342 for ABCB1 (also known as P-gp and MDR1) and ABCG2 (BCRP1). In this chapter, we will describe the complete procedure for the detection of MDR activity, including: (1) Preparing single-cell suspensions from tumor and normal tissue specimens; (2) An efficient method to perform cell surface marker staining on large numbers of cells; (3) Flow cytometer setup and controls; (4) Simultaneous measurement of Hoechst 33342 and Rhodamine123 transport; and (5) Data acquisition and analysis.

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The Telomerase Activity of Adult Mouse Testis Resides in the Spermatogonial α6-Integrin-Positive Side Population Enriched in Germinal Stem Cells

Cited by 30 publications

References 36 publications

High telomerase is a hallmark of undifferentiated spermatogonia and is required for maintenance of male germline stem cells

High telomerase is a hallmark of undifferentiated spermatogonia and is required for maintenance of male germline stem cells

Integrins in the Spotlight of Cancer

Measurement of Multiple Drug Resistance Transporter Activity in Putative Cancer Stem/Progenitor Cells

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