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Spatial regulation of Drosophila ovarian Follicle Stem Cell division rates and cell cycle transitions

Drosophila ovarian Follicle Stem Cells (FSCs) present a favorable paradigm for understanding how stem cell division and differentiation are balanced in communities where those activities are independent. FSCs also allow exploration of how this balance is integrated with spatial stem cell heterogenei...

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Autores principales: Melamed, David, Choi, Aaron, Reilein, Amy, Tavaré, Simon, Kalderon, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10553835/
https://www.ncbi.nlm.nih.gov/pubmed/37747936
http://dx.doi.org/10.1371/journal.pgen.1010965
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author Melamed, David
Choi, Aaron
Reilein, Amy
Tavaré, Simon
Kalderon, Daniel
author_facet Melamed, David
Choi, Aaron
Reilein, Amy
Tavaré, Simon
Kalderon, Daniel
author_sort Melamed, David
collection PubMed
description Drosophila ovarian Follicle Stem Cells (FSCs) present a favorable paradigm for understanding how stem cell division and differentiation are balanced in communities where those activities are independent. FSCs also allow exploration of how this balance is integrated with spatial stem cell heterogeneity. Posterior FSCs become proliferative Follicle Cells (FCs), while anterior FSCs become quiescent Escort Cells (ECs) at about one fourth the frequency. A single stem cell can nevertheless produce both FCs and ECs because it can move between anterior and posterior locations. Studies based on EdU incorporation to approximate division rates suggested that posterior FSCs divide faster than anterior FSCs. However, direct measures of cell cycle times are required to ascertain whether FC output requires a net flow of FSCs from anterior to posterior. Here, by using live imaging and FUCCI cell-cycle reporters, we measured absolute division rates. We found that posterior FSCs cycle more than three times faster than anterior FSCs and produced sufficient new cells to match FC production. H2B-RFP dilution studies supported different cycling rates according to A/P location and facilitated live imaging, showing A/P exchange of FSCs in both directions, consistent with the dynamic equilibrium inferred from division rate measurements. Inversely graded Wnt and JAK-STAT pathway signals regulate FSC differentiation to ECs and FCs. JAK-STAT promotes both differentiation to FCs and FSC cycling, affording some coordination of these activities. When JAK-STAT signaling was manipulated to be spatially uniform, the ratio of posterior to anterior division rates was reduced but remained substantial, showing that graded JAK-STAT signaling only partly explains the graded cycling of FSCs. By using FUCCI markers, we found a prominent G2/M cycling restriction of posterior FSCs together with an A/P graded G1/S restriction, that JAK-STAT signaling promotes both G1/S and G2/M transitions, and that PI3 kinase signaling principally stimulates the G2/M transition.
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spelling pubmed-105538352023-10-06 Spatial regulation of Drosophila ovarian Follicle Stem Cell division rates and cell cycle transitions Melamed, David Choi, Aaron Reilein, Amy Tavaré, Simon Kalderon, Daniel PLoS Genet Research Article Drosophila ovarian Follicle Stem Cells (FSCs) present a favorable paradigm for understanding how stem cell division and differentiation are balanced in communities where those activities are independent. FSCs also allow exploration of how this balance is integrated with spatial stem cell heterogeneity. Posterior FSCs become proliferative Follicle Cells (FCs), while anterior FSCs become quiescent Escort Cells (ECs) at about one fourth the frequency. A single stem cell can nevertheless produce both FCs and ECs because it can move between anterior and posterior locations. Studies based on EdU incorporation to approximate division rates suggested that posterior FSCs divide faster than anterior FSCs. However, direct measures of cell cycle times are required to ascertain whether FC output requires a net flow of FSCs from anterior to posterior. Here, by using live imaging and FUCCI cell-cycle reporters, we measured absolute division rates. We found that posterior FSCs cycle more than three times faster than anterior FSCs and produced sufficient new cells to match FC production. H2B-RFP dilution studies supported different cycling rates according to A/P location and facilitated live imaging, showing A/P exchange of FSCs in both directions, consistent with the dynamic equilibrium inferred from division rate measurements. Inversely graded Wnt and JAK-STAT pathway signals regulate FSC differentiation to ECs and FCs. JAK-STAT promotes both differentiation to FCs and FSC cycling, affording some coordination of these activities. When JAK-STAT signaling was manipulated to be spatially uniform, the ratio of posterior to anterior division rates was reduced but remained substantial, showing that graded JAK-STAT signaling only partly explains the graded cycling of FSCs. By using FUCCI markers, we found a prominent G2/M cycling restriction of posterior FSCs together with an A/P graded G1/S restriction, that JAK-STAT signaling promotes both G1/S and G2/M transitions, and that PI3 kinase signaling principally stimulates the G2/M transition. Public Library of Science 2023-09-25 /pmc/articles/PMC10553835/ /pubmed/37747936 http://dx.doi.org/10.1371/journal.pgen.1010965 Text en © 2023 Melamed et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Melamed, David
Choi, Aaron
Reilein, Amy
Tavaré, Simon
Kalderon, Daniel
Spatial regulation of Drosophila ovarian Follicle Stem Cell division rates and cell cycle transitions
title Spatial regulation of Drosophila ovarian Follicle Stem Cell division rates and cell cycle transitions
title_full Spatial regulation of Drosophila ovarian Follicle Stem Cell division rates and cell cycle transitions
title_fullStr Spatial regulation of Drosophila ovarian Follicle Stem Cell division rates and cell cycle transitions
title_full_unstemmed Spatial regulation of Drosophila ovarian Follicle Stem Cell division rates and cell cycle transitions
title_short Spatial regulation of Drosophila ovarian Follicle Stem Cell division rates and cell cycle transitions
title_sort spatial regulation of drosophila ovarian follicle stem cell division rates and cell cycle transitions
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10553835/
https://www.ncbi.nlm.nih.gov/pubmed/37747936
http://dx.doi.org/10.1371/journal.pgen.1010965
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