Opposing JAK-STAT and Wnt signaling gradients define a stem cell domain by regulating differentiation at two borders DOI Creative Commons
David Melamed, Daniel Kalderon

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Nov. 2, 2020

Many adult stem cell communities are maintained by population asymmetry, where stochastic behaviors of multiple individual cells collectively result in a balance between division and differentiation. We investigated how this is achieved for Drosophila Follicle Stem Cells (FSCs) spatially-restricted niche signals. FSCs produce transit-amplifying (FCs) from their posterior face quiescent Escort (ECs) to anterior. show that JAK-STAT pathway activity, which declines anterior, dictates the pattern divisions over FSC domain, promotes more locations conversion FCs, while opposing EC production. Wnt activity anterior production, opposes FC The pathways combine define domain through concerted effects on differentiation ECs FCs at either end signaling gradients, impose proliferation matches derivative production.Adult organisms contain variety routinely replaced using can generate specific tissue. These often clustered into small groups, combinations chemical signals nearby encourage each divide or ‘differentiate’ another type cell. different must somehow maintain size shape community. ovary an fruit fly contains group called follicle cells, short. support continual production eggs supplying two types opposite faces cluster: dividing emerge back cluster guide late egg development, non-dividing escort come front early development. Two control graded cluster. strongest territory gradually towards front, absent cells. However, it was unclear gradients these formation To answer question, Melamed Kalderon used genetic engineering modify strength experiments measured affected rate converted found dictated rates, may explain why varies across do not all. also stimulated become opposed Conversely, stronger favored inhibited transitioning This suggests relative helps thecorrect number balancing JAK-STAT, other development many organisms, including humans, have been linked cancer. Therefore, principles mechanisms uncovered apply Furthermore, work highlights changes allow mutant amplify take entire community, play role cancer illnesses.

Language: Английский

Opposing Action of Hedgehog and Insulin Signaling Balances Proliferation and Autophagy to Determine Follicle Stem Cell Lifespan DOI Creative Commons
Tanu Singh, Eric H. Lee, Tiffiney R. Hartman

et al.

Developmental Cell, Journal Year: 2018, Volume and Issue: 46(6), P. 720 - 734.e6

Published: Sept. 1, 2018

Language: Английский

Citations

26

Non‐apoptotic caspase activation ensures the homeostasis of ovarian somatic stem cells DOI Creative Commons
Alessia Galasso, Derek Xu, Claire Hill

et al.

EMBO Reports, Journal Year: 2023, Volume and Issue: 24(6)

Published: April 11, 2023

Current evidence has associated caspase activation with the regulation of basic cellular functions without causing apoptosis. Malfunction non-apoptotic activities may contribute to specific neurological disorders, metabolic diseases, autoimmune conditions and cancers. However, our understanding remains limited. Here, we show that prevents intracellular accumulation Patched receptor in autophagosomes subsequent Patched-dependent induction autophagy Drosophila follicular stem cells. These events ultimately sustain Hedgehog signalling physiological properties ovarian somatic cells their progeny under moderate thermal stress. Importantly, key findings are partially conserved human origin. observations attribute caspases a pro-survival role certain conditions.

Language: Английский

Citations

7

Interkinetic nuclear migration and basal tethering facilitates post-mitotic daughter separation in intestinal organoids DOI Creative Commons
Thomas Carroll,

Alistair Langlands,

James M. Osborne

et al.

Journal of Cell Science, Journal Year: 2017, Volume and Issue: 130(22), P. 3862 - 3877

Published: Oct. 12, 2017

Homeostasis of renewing tissues requires balanced proliferation, differentiation and movement. This is particularly important in the intestinal epithelium where lineage tracing suggests that stochastic choices are intricately coupled to position a cell relative niche. To determine how achieved, we followed proliferating cells organoids discovered behaviour mitotic sisters predicted long-term positioning. We found that, normally, 70% remain neighbours, while 30% lose contact separate after cytokinesis. These post-mitotic placements predict longer term differences positions assumed by sisters: adjacent reach similar over time; pair separating sisters, one remains close its birthplace other displaced upward. Computationally modelling crypt dynamics confirmed separation leads reaching different compartments. show interkinetic nuclear migration, size asymmetric tethering process extending from basal side contribute separations. processes altered adenomatous polyposis coli (Apc) mutant epithelia lost. conclude placement contributes niche exit and, when defective, supports clonal expansion Apc cells.

Language: Английский

Citations

23

Collective Cell Sorting Requires Contractile Cortical Waves in Germline Cells DOI Creative Commons
Soline Chanet, Jean‐René Huynh

Current Biology, Journal Year: 2020, Volume and Issue: 30(21), P. 4213 - 4226.e4

Published: Sept. 10, 2020

Language: Английский

Citations

20

Opposing JAK-STAT and Wnt signaling gradients define a stem cell domain by regulating differentiation at two borders DOI Creative Commons
David Melamed, Daniel Kalderon

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Nov. 2, 2020

Many adult stem cell communities are maintained by population asymmetry, where stochastic behaviors of multiple individual cells collectively result in a balance between division and differentiation. We investigated how this is achieved for Drosophila Follicle Stem Cells (FSCs) spatially-restricted niche signals. FSCs produce transit-amplifying (FCs) from their posterior face quiescent Escort (ECs) to anterior. show that JAK-STAT pathway activity, which declines anterior, dictates the pattern divisions over FSC domain, promotes more locations conversion FCs, while opposing EC production. Wnt activity anterior production, opposes FC The pathways combine define domain through concerted effects on differentiation ECs FCs at either end signaling gradients, impose proliferation matches derivative production.Adult organisms contain variety routinely replaced using can generate specific tissue. These often clustered into small groups, combinations chemical signals nearby encourage each divide or ‘differentiate’ another type cell. different must somehow maintain size shape community. ovary an fruit fly contains group called follicle cells, short. support continual production eggs supplying two types opposite faces cluster: dividing emerge back cluster guide late egg development, non-dividing escort come front early development. Two control graded cluster. strongest territory gradually towards front, absent cells. However, it was unclear gradients these formation To answer question, Melamed Kalderon used genetic engineering modify strength experiments measured affected rate converted found dictated rates, may explain why varies across do not all. also stimulated become opposed Conversely, stronger favored inhibited transitioning This suggests relative helps thecorrect number balancing JAK-STAT, other development many organisms, including humans, have been linked cancer. Therefore, principles mechanisms uncovered apply Furthermore, work highlights changes allow mutant amplify take entire community, play role cancer illnesses.

Language: Английский

Citations

19