white regulates proliferative homeostasis of intestinal stem cells during ageing in Drosophila

Sasaki, A; Nishimura, Takashi; Takano, Tomomi; Naito, Saki; Yoo, Sa Kan

doi:10.1038/s42255-021-00375-x

Cited by 34 publications

(30 citation statements)

References 52 publications

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“…In parallel with pathological changes analysed by imaging, gut barrier function can be assessed using well-described methods to detect the onset of gut leakiness 34,35 . As previously reported 16,28,29 , females treated with rapamycin showed a strong attenuation of dysplastic epithelial 37 .…”

Section: Age-related Gut Pathology Is Reduced In Females Treated With Rapamycinsupporting

confidence: 86%

Sexual identity of enterocytes regulates rapamycin-mediated intestinal homeostasis and lifespan extension

Regan

Ureña

et al. 2021

Preprint

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Pharmacological attenuation of mTOR by rapamycin and other compounds presents a promising route for delay of ageing-related pathologies, including intestinal cancers. Here, we show that rapamycin treatment in Drosophila extends lifespan in females but not in males. Female-specific, age-related gut pathology and impaired intestinal barrier function are both markedly slowed by rapamycin treatment, mediated by increased autophagy. Upon rapamycin treatment, female intestinal enterocytes increase autophagy, via the H3/H4 histone-Bchs axis, while male enterocytes show high basal levels of autophagy that do not increase further upon rapamycin treatment. Sexual identity of enterocytes alone, determined by the expression of transformerFemale, dictates sexually dimorphic cell size, H3/H4-Bchs expression, basal rates of autophagy, fecundity, intestinal homeostasis and extension of lifespan in response to rapamycin. This study highlights that tissue sex determines regulation of metabolic processes by mTOR and the efficacy of mTOR-targeted, anti-ageing drug treatments.

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Section: Age-related Gut Pathology Is Reduced In Females Treated With Rapamycinsupporting

confidence: 86%

Sexual identity of enterocytes regulates rapamycin-mediated intestinal homeostasis and lifespan extension

Regan

Ureña

et al. 2021

Preprint

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“…However, the ability of white to form multiple functional heterodimers indicates that this protein could potentially affect many different cellular processes. White has been implicated in the transport of pyruvate, riboflavin, xanthine, guanosine, and zinc [ 46 , 47 , 73 , 74 , 75 , 76 ]. In most of these cases, white is involved in concentrating these compounds into vesicles [ 46 , 47 , 74 , 75 ].…”

Section: Discussionmentioning

confidence: 99%

Mutants of the white ABCG Transporter in Drosophila melanogaster Have Deficient Olfactory Learning and Cholesterol Homeostasis

Myers

Porter

Narwold

et al. 2021

IJMS

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Drosophila’s white gene encodes an ATP-binding cassette G-subfamily (ABCG) half-transporter. White is closely related to mammalian ABCG family members that function in cholesterol efflux. Mutants of white have several behavioral phenotypes that are independent of visual defects. This study characterizes a novel defect of white mutants in the acquisition of olfactory memory using the aversive olfactory conditioning paradigm. The w1118 mutants learned slower than wildtype controls, yet with additional training, they reached wildtype levels of performance. The w1118 learning phenotype is also found in the wapricot and wcoral alleles, is dominant, and is rescued by genomic white and mini-white transgenes. Reducing dietary cholesterol strongly impaired olfactory learning for wildtype controls, while w1118 mutants were resistant to this deficit. The w1118 mutants displayed higher levels of cholesterol and cholesterol esters than wildtype under this low-cholesterol diet. Increasing levels of serotonin, dopamine, or both in the white mutants significantly improved w1118 learning. However, serotonin levels were not lower in the heads of the w1118 mutants than in wildtype controls. There were also no significant differences found in synapse numbers within the w1118 brain. We propose that the w1118 learning defect may be due to inefficient biogenic amine signaling brought about by altered cholesterol homeostasis.

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“…Sometimes, more or less gratuitous genetic markers are employed in crosses of fruit flies in order to ease the trace back of mutant alleles of the genes of interest. In our case, both γCOP 14a / γCOP 14a and γCOP S057302 /TM6B males have constitutively hemizygous mutations for white , a gene located in the X chromosome and recently reported to be involved not only in red eye pigmentation, but also in the response to some metabolic and cellular stresses [ 36 , 37 ]. To date, there is no information indexed in FlyBase to support or suggest that white is involved either in the immune response of flies or in interactions with γCOP or COPI.…”

Section: Discussionmentioning

confidence: 72%

Mutations of γCOP Gene Disturb Drosophila melanogaster Innate Immune Response to Pseudomonas aeruginosa

Chifiriuc

Bologa

Rațiu

et al. 2022

IJMS

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Drosophila melanogaster (the fruit fly) is a valuable experimental platform for modeling host–pathogen interactions. It is also commonly used to define innate immunity pathways and to understand the mechanisms of both host tolerance to commensal microbiota and response to pathogenic agents. Herein, we investigate how the host response to bacterial infection is mirrored in the expression of genes of Imd and Toll pathways when D. melanogaster strains with different γCOP genetic backgrounds are infected with Pseudomonas aeruginosa ATCC 27853. Using microarray technology, we have interrogated the whole-body transcriptome of infected versus uninfected fruit fly males with three specific genotypes, namely wild-type Oregon, γCOPS057302/TM6B and γCOP14a/γCOP14a. While the expression of genes pertaining to Imd and Toll is not significantly modulated by P. aeruginosa infection in Oregon males, many of the components of these cascades are up or downregulated in both infected and uninfected γCOPS057302/TM6B and γCOP14a/γCOP14a males. Thus, our results suggest that a γCOP genetic background modulates the gene expression profiles of Imd and Toll cascades involved in the innate immune response of D. melanogaster, inducing the occurrence of immunological dysfunctions in γCOP mutants.

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white regulates proliferative homeostasis of intestinal stem cells during ageing in Drosophila

Cited by 34 publications

References 52 publications

Sexual identity of enterocytes regulates rapamycin-mediated intestinal homeostasis and lifespan extension

Sexual identity of enterocytes regulates rapamycin-mediated intestinal homeostasis and lifespan extension

Mutants of the white ABCG Transporter in Drosophila melanogaster Have Deficient Olfactory Learning and Cholesterol Homeostasis

Mutations of γCOP Gene Disturb Drosophila melanogaster Innate Immune Response to Pseudomonas aeruginosa

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