Amoyel, M;
Hillion, K-H;
Margolis, SR;
Bach, EA;
(2016)
Somatic stem cell differentiation is regulated by PI3K/Tor signaling in response to local cues.
Development
, 143
(21)
pp. 3914-3925.
10.1242/dev.139782.
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Abstract
Stem cells reside in niches that provide signals to maintain self-renewal, and differentiation is viewed as a passive process that depends on loss of access to these signals. Here, we demonstrate that the differentiation of somatic cyst stem cells (CySCs) in the Drosophila testis is actively promoted by PI3K/Tor signaling, as CySCs lacking PI3K/Tor activity cannot differentiate properly. We find that an insulin peptide produced by somatic cells immediately outside of the stem cell niche acts locally to promote somatic differentiation through Insulin-like receptor (InR) activation. These results indicate that there is a local ‘differentiation' niche that upregulates PI3K/Tor signaling in the early daughters of CySCs. Finally, we demonstrate that CySCs secrete the Dilp-binding protein ImpL2, the Drosophila homolog of IGFBP7, into the stem cell niche, which blocks InR activation in CySCs. Thus, we show that somatic cell differentiation is controlled by PI3K/Tor signaling downstream of InR and that the local production of positive and negative InR signals regulates the differentiation niche. These results support a model in which leaving the stem cell niche and initiating differentiation are actively induced by signaling.
| Type: | Article |
|---|---|
| Title: | Somatic stem cell differentiation is regulated by PI3K/Tor signaling in response to local cues |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1242/dev.139782 |
| Publisher version: | https://doi.org/10.1242/dev.139782 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Developmental Biology, PI3K, Tor, Insulin, Stem cell differentiation, Drosophila, Testis, DROSOPHILA INSULIN-RECEPTOR, SELF-RENEWAL, GROWTH-CONTROL, MAMMALIAN TARGET, TUMOR-SUPPRESSOR, SUPPORT CELLS, LIFE-SPAN, GERMLINE, NICHE, RAPAMYCIN |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10059399 |
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