Dynamic Hedgehog signalling pathway activity in germline stem cells

Zeliha Sahin, Anette Szczepny, Eileen Anne McLaughlin, Marvin L Meistrich, Wei Zhou, Ismail Ustunel, Katherine Ann Lakoski Loveland

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Although the contribution of Hedgehog (Hh) signalling to stem cell development and oncogenesis is well recognised, its importance for spermatogonial stem cells (SSCs) has not been established. Here we interrogate adult rat SSCs using an established model in which only undifferentiated spermatogonial cells remain in the testis at 15 weeks following irradiation, and spermatogonial differentiation is induced within 4 weeks by gonadotrophin-releasing hormone antagonist (GnRH-ant) administration. Synthesis of Hh pathway components in untreated adult rat testes was compared with that in irradiated testes prior to and after GnRH-ant exposure using in situ hybridization. In adult testes with complete spermatogenesis, the Desert Hedgehog ligand transcript, Dhh, was detected in Sertoli cells, some spermatogonia and in spermatocytes by in situ hybridization. Spermatogenic cells were identified as sites of Hh signalling through detection of transcripts encoding the Hh receptor, Ptc2 transcripts and proteins for the key downstream target of Hh signalling, Gli1 and the Hh transcriptional activator, Gli2. Remarkably, the undifferentiated spermatogonia present in irradiated adult rat testes contained Dhh in addition to Ptc2, Gli1 and Gli2, revealing the potential for an autocrine Hh signalling loop to sustain undifferentiated spermatogonial cells. These transcripts became undetectable by in situ hybridization following GnRH-ant induction of spermatogonial differentiation, however, detection of Gli1 protein in spermatogonia in all groups indicates that Hh signalling is sustained. This is the first evidence of active Hh signalling in mammalian male germline stem cells, as has been documented for some cancer stem cells.
Original languageEnglish
Pages (from-to)267 - 274
Number of pages8
JournalAndrology
Volume2
Issue number2
DOIs
Publication statusPublished - 2014

Cite this

Sahin, Z., Szczepny, A., McLaughlin, E. A., Meistrich, M. L., Zhou, W., Ustunel, I., & Loveland, K. A. L. (2014). Dynamic Hedgehog signalling pathway activity in germline stem cells. Andrology, 2(2), 267 - 274. https://doi.org/10.1111/j.2047-2927.2014.00187.x
Sahin, Zeliha ; Szczepny, Anette ; McLaughlin, Eileen Anne ; Meistrich, Marvin L ; Zhou, Wei ; Ustunel, Ismail ; Loveland, Katherine Ann Lakoski. / Dynamic Hedgehog signalling pathway activity in germline stem cells. In: Andrology. 2014 ; Vol. 2, No. 2. pp. 267 - 274.
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Sahin, Z, Szczepny, A, McLaughlin, EA, Meistrich, ML, Zhou, W, Ustunel, I & Loveland, KAL 2014, 'Dynamic Hedgehog signalling pathway activity in germline stem cells', Andrology, vol. 2, no. 2, pp. 267 - 274. https://doi.org/10.1111/j.2047-2927.2014.00187.x

Dynamic Hedgehog signalling pathway activity in germline stem cells. / Sahin, Zeliha; Szczepny, Anette; McLaughlin, Eileen Anne; Meistrich, Marvin L; Zhou, Wei; Ustunel, Ismail; Loveland, Katherine Ann Lakoski.

In: Andrology, Vol. 2, No. 2, 2014, p. 267 - 274.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Sahin, Zeliha

AU - Szczepny, Anette

AU - McLaughlin, Eileen Anne

AU - Meistrich, Marvin L

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AU - Ustunel, Ismail

AU - Loveland, Katherine Ann Lakoski

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UR - http://www.ncbi.nlm.nih.gov/pubmed/24574096

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Sahin Z, Szczepny A, McLaughlin EA, Meistrich ML, Zhou W, Ustunel I et al. Dynamic Hedgehog signalling pathway activity in germline stem cells. Andrology. 2014;2(2):267 - 274. https://doi.org/10.1111/j.2047-2927.2014.00187.x