Opposing Action of Hedgehog and Insulin Signaling Balances Proliferation and Autophagy to Determine Follicle Stem Cell Lifespan

Singh, Tanu; Lee, Eric H.; Hartman, Tiffiney R.; Ruiz-Whalen, Dara M.; O’Reilly, Alana M.

doi:10.1016/j.devcel.2018.08.008

Cited by 21 publications

(43 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6J). These observations provide further confirmation of our current FSC model and are clearly not consistent with either the original models postulating just two FSCs in a single layer (Fadiga and Nystul, 2019;Margolis and Spradling, 1995;Spradling, 2007, 2010) or recent postulates of an intermediate model where FSCs occupy the full circumference of the germarium but only in layer 2 (Singh et al, 2018).…”

Section: Verification Of the Organization Of Fscscontrasting

confidence: 72%

Opposing JAK-STAT and Wnt signaling gradients define a stem cell domain by regulating differentiation at two borders

Melamed

Kalderon

2020

eLife

View full text Add to dashboard Cite

Many adult stem cell communities are maintained by population asymmetry, where stochastic behaviors of multiple individual cells collectively result in a balance between stem cell division and differentiation. We investigated how this is achieved for Drosophila Follicle Stem Cells (FSCs) by spatially-restricted niche signals. FSCs produce transit-amplifying Follicle Cells (FCs) from their posterior face and quiescent Escort Cells (ECs) to their anterior. We show that JAK-STAT pathway activity, which declines from posterior to anterior, dictates the pattern of divisions over the FSC domain, promotes more posterior FSC locations and conversion to FCs, while opposing EC production. Wnt pathway activity declines from the anterior, promotes anterior FSC locations and EC production, and opposes FC production. The pathways combine to define a stem cell domain through concerted effects on FSC differentiation to ECs and FCs at either end of opposing signaling gradients, and impose a pattern of proliferation that matches derivative production.

show abstract

Section: Verification Of the Organization Of Fscscontrasting

confidence: 72%

Opposing JAK-STAT and Wnt signaling gradients define a stem cell domain by regulating differentiation at two borders

Melamed

Kalderon

2020

eLife

View full text Add to dashboard Cite

show abstract

“…Whereas the activation of autophagy reduces the intracellular levels of Ref2P/p62, its inhibition facilitates Ref2P/p62 accumulation 44 . In agreement with the previous literature 14,42 , the expression of Ref2P increased in a genetic condition that modestly reduced Ptc protein levels ( ptc -Gal4/+) (Figs. 6a-c).…”

Section: Resultssupporting

confidence: 93%

“…In addition to the Hh-regulatory role, Ptc can induce autophagy in ovarian somatic cells from Drosophila and mammals 14,42 . Therefore, we investigated whether Ptc aggregates observed in our mutant conditions were able to induce autophagy.…”

Section: Resultsmentioning

confidence: 99%

“…Beyond repressing Hh-signalling, the accumulation of Ptc in Dronc mutant follicular cells can induce autophagy 14,42 (Fig. 6).…”

Section: Discussionmentioning

confidence: 99%

“…As opposed to Hh-signalling deprivation 6,8,10 , the overactivation of Hh-pathway facilitates cell proliferation and cell differentiation in the follicular stem cells and their progeny 8,11,13,14 . Beyond the developmental requirements, Hh-signalling also prevents the excess of Ptc-induced autophagy under stress conditions, thus ensuring the homeostasis of ovarian somatic cells 14,15 . Importantly, the pro-proliferative and differentiating roles of Hh-pathway are largely conserved in human ovarian cells with somatic origin 16–19 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Non-apoptotic caspase activation sustains ovarian somatic stem cell functions by modulating Hedgehog-signalling and autophagy

Galasso

Iakovleva²,

Baena‐López

2019

Preprint

View full text Add to dashboard Cite

ABSTRACTThere is increasing evidence associating the activity of caspases with the regulation of basic cellular functions beyond apoptosis. Accordingly, the dysregulation of these novel non-apoptotic functions often sits at the origin of neurological disorders, metabolic defects, autoimmunity, and cancer. However, the molecular interplay between caspases and the signalling networks active in non-apoptotic cellular scenarios remains largely unknown. Our experiments show that non-apoptotic caspase activation is critical to modulate Hedgehog-signalling and autophagy in ovarian somatic cells from both Drosophila and humans under moderate stress. We also demonstrate that these novel caspase functions are key to sustain stem cell proliferation and differentiation without inducing apoptosis. Finally, we molecularly link these caspase-dependent effects to the fine-tuning of the Hedgehog-receptor, Patched. Together, these findings confer a pro-survival role to the caspases, as opposed to the widely held apoptotic function assigned to these enzymes for many years.

show abstract

MicroRNA‐524‐5p suppresses the progression of papillary thyroid carcinoma cells via targeting on FOXE1 and ITGA3 in cell autophagy and cycling pathways

Liu

Chen

Lin

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

MicroRNAs are beneficial for cancer therapy as they can simultaneously downregulate multiple targets involved in diverse biological pathways related to tumor development. In papillary thyroid cancer, many microRNAs were identified as differentially expressed factors in tumor tissues. In another way, recent studies revealed cell proliferation, cell cycling, apoptosis, and autophagy are critical pathways controlling papillary thyroid cancer development and progression. As miR‐524‐5p was approved as a cancer suppressor targeting multiple genes in several types of cancer cells, this study aims to characterize the role of miR‐524‐5p in the thyroid cancer cell. The expression of miR‐524‐5p was decreased in the papillary thyroid cancer tissues and cell lines, while forkhead box E1 (FOXE1) and ITGA3 were increased. In the clinical case, expression of miR‐524‐5p, FOXE1, and ITGA3 were significantly correlated with papillary thyroid cancer development and progression. FOXE1 and ITGA3 were approved as direct targets of miR‐524‐5p. miR‐524‐5p could inhibit papillary thyroid cancer cell viability, migration, invasion, and apoptosis through targeting FOXE1 and ITGA3. Cell cycling and autophagy pathways were disturbed by downregulation of FOXE1 and ITGA3, respectively. Collectively, miR‐524‐5p targeting on FOXE1 and ITGA3 prevents thyroid cancer progression through different pathways including cell cycling and autophagy.

show abstract

Opposing Action of Hedgehog and Insulin Signaling Balances Proliferation and Autophagy to Determine Follicle Stem Cell Lifespan

Cited by 21 publications

References 69 publications

Opposing JAK-STAT and Wnt signaling gradients define a stem cell domain by regulating differentiation at two borders

Opposing JAK-STAT and Wnt signaling gradients define a stem cell domain by regulating differentiation at two borders

Non-apoptotic caspase activation sustains ovarian somatic stem cell functions by modulating Hedgehog-signalling and autophagy

MicroRNA‐524‐5p suppresses the progression of papillary thyroid carcinoma cells via targeting on FOXE1 and ITGA3 in cell autophagy and cycling pathways

Contact Info

Product

Resources

About