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TGF-beta Sma/Mab signaling regulates a set of genes in oocytes associated with reproductive aging and another set in L4 associated with body size growth

ABSTRACT: Reproductive cessation is perhaps the earliest aging phenotypes humans experience. Similarly, C. elegans' reproduction ceases in mid-adulthood. Although somatic aging has been studied in both worms and humans, mechanisms regulating reproductive aging are not yet understood. Here we show that TGF-beta Sma/Mab activity regulates reproductive aging transcriptionally separable from its regulation of body size growth. This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE23509 | GEO | 2010/09/01

SECONDARY ACCESSION(S): PRJNA131083

REPOSITORIES: GEO

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TGF-beta Sma/Mab signaling regulates a set of genes in oocytes associated with reproductive aging and another set in L4 associated with body size growth

Project description:Reproductive cessation is perhaps the earliest aging phenotypes humans experience. Similarly, C. elegans' reproduction ceases in mid-adulthood. Although somatic aging has been studied in both worms and humans, mechanisms regulating reproductive aging are not yet understood. Here we show that TGF-beta Sma/Mab activity regulates reproductive aging transcriptionally separable from its regulation of body size growth. This SuperSeries is composed of the following subset Series: GSE23446: Reproductive aging: sma-2;fem-1 day 8 oocyte vs fem-1 day 8 oocyte GSE23447: Reproductive aging: fem-1 day 3 oocyte vs fem-1 day 8 oocyte GSE23448: Body size regulation and TGF-beta Sma/Mab pathway: sma L4 vs N2 L4 Refer to individual Series

2010-09-01 | E-GEOD-23509 | biostudies-arrayexpress

Body size regulation and TGF-beta Sma/Mab pathway: sma L4 vs N2 L4

Project description:To find genes downstream of the TGF-beta Sma/Mab pathway associated with body size regulation in C. elegans.

2010-09-01 | GSE23448 | GEO

Body size regulation and TGF-beta Sma/Mab pathway: sma L4 vs N2 L4

Project description:To find genes downstream of the TGF-beta Sma/Mab pathway associated with body size regulation in C. elegans. Three replicates comparing RNA from sma-2(e502) L4 whole animal with RNA from wild-type L4 whole animal, in which one is dye flipped. Plus one array comparing RNA from sma-4(e729) L4 whole animal with RNA from wild-type L4 whole animal.

2010-09-01 | E-GEOD-23448 | biostudies-arrayexpress

Reproductive aging: sma-2;fem-1 day 8 oocyte vs fem-1 day 8 oocyte

Project description:To find genes downstream of the TGF-beta Sma/Mab pathway in C. elegans oocytes associated with reproductive aging.

2010-09-01 | GSE23446 | GEO

Reproductive aging: sma-2;fem-1 day 8 oocyte vs fem-1 day 8 oocyte

Project description:To find genes downstream of the TGF-beta Sma/Mab pathway in C. elegans oocytes associated with reproductive aging. Eight replicates comparing RNA from oocyte samples collected from day 8 sma-2(e502);fem-1(hc17) animals with RNA from oocyte samples collected from day 8 fem-1(hc17) animals. Five out of eight are dye-flipped.

2010-09-01 | E-GEOD-23446 | biostudies-arrayexpress

TGF-beta Sma/Mab signaling mutations uncouple reproductive aging from somatic aging.

Project description:Female reproductive cessation is one of the earliest age-related declines humans experience, occurring in mid-adulthood. Similarly, Caenorhabditis elegans' reproductive span is short relative to its total life span, with reproduction ceasing about a third into its 15-20 day adulthood. All of the known mutations and treatments that extend C. elegans' reproductive period also regulate longevity, suggesting that reproductive span is normally linked to life span. C. elegans has two canonical TGF-beta signaling pathways. We recently found that the TGF-beta Dauer pathway regulates longevity through the Insulin/IGF-1 Signaling (IIS) pathway; here we show that this pathway has a moderate effect on reproductive span. By contrast, TGF-beta Sma/Mab signaling mutants exhibit a substantially extended reproductive period, more than doubling reproductive span in some cases. Sma/Mab mutations extend reproductive span disproportionately to life span and act independently of known regulators of somatic aging, such as Insulin/IGF-1 Signaling and Dietary Restriction. This is the first discovery of a pathway that regulates reproductive span independently of longevity and the first identification of the TGF-beta Sma/Mab pathway as a regulator of reproductive aging. Our results suggest that longevity and reproductive span regulation can be uncoupled, although they appear to normally be linked through regulatory pathways.

| S-EPMC2791159 | biostudies-literature

FIGfams: yet another set of protein families.

Project description:We present FIGfams, a new collection of over 100,000 protein families that are the product of manual curation and close strain comparison. Using the Subsystem approach the manual curation is carried out, ensuring a previously unattained degree of throughput and consistency. FIGfams are based on over 950,000 manually annotated proteins and across many hundred Bacteria and Archaea. Associated with each FIGfam is a two-tiered, rapid, accurate decision procedure to determine family membership for new proteins. FIGfams are freely available under an open source license. These can be downloaded at ftp://ftp.theseed.org/FIGfams/. The web site for FIGfams is http://www.theseed.org/wiki/FIGfams/

| S-EPMC2777423 | biostudies-other

Single-oocyte transcriptome analysis reveals aging-associated effects influenced by life stage and calorie restriction

Project description:Chromosome segregation errors in oocytes lead to the production of aneuploid eggs, which are the leading cause of pregnancy loss and of several congenital diseases such as Down syndrome. The frequency of chromosome segregation errors in oocytes increases with maternal age, especially at a late stage of reproductive life. How aging at various life stages affects oocytes differently remains poorly understood. In this study, we describe aging-associated changes in the transcriptome profile of mouse oocytes throughout reproductive life. Our single-oocyte comprehensive RNA sequencing using RamDA-seq revealed that oocytes undergo transcriptome changes at a late reproductive stage, whereas their surrounding cumulus cells exhibit transcriptome changes at an earlier stage. Calorie restriction, a paradigm that reportedly prevents aging-associated egg aneuploidy, promotes a transcriptome shift in oocytes with the up-regulation of genes involved in chromosome segregation. This shift is accompanied by the improved maintenance of chromosomal cohesin, the loss of which is a hallmark of oocyte aging and causes chromosome segregation errors. These findings have implications for understanding how oocytes undergo aging-associated functional decline throughout their reproductive life in a context-dependent manner.

2021-08-02 | GSE159281 | GEO

SMA-10 Is a Non-Canonical Member of the TGF-β Sma/Mab Pathway and Immunity Regulator via the DAF-2 Insulin Receptor in Caenorhabditis elegans.

Project description:Transforming growth factor β (TGF-β) signalling pathways are highly conserved across metazoa and play essential roles not only during development but also in adult tissue maintenance. Alterations of these pathways usually result in a plethora of pathologies. In the nematode Caenorhabditis elegans, the TGF-β Sma/Mab (small/male abnormal) pathway regulates various worm phenotypes such as body size, immune response, ageing, matricide and reproductive span. SMA-10 has been described as a positive modulator of worm body size through the TGF-β Sma/Mab pathway. To better understand if SMA-10 is a core component of the pathway, we use gene epistatic analysis to assess the contribution of SMA-10 to various phenotypes regulated by TGF-β Sma/Mab. We confirm that SMA-10 controls body size and find that it also affects the matricide and reproductive span of the nematodes. However, neither male tail formation (previously reported) nor ageing appeared altered. Lastly, although null sma-10 worms are more susceptible to Pseudomonas aeruginosa infections than wild-types, this response does not depend on TGF-β Sma/Mab but on the insulin receptor DAF-2. We also show that the expression of sma-10 in either hypodermis or intestine fully rescues the wild-type immune response. Our results contribute to understanding the role of SMA-10 as a context-dependent component of TGF-β Sma/Mab, and reveal a function of SMA-10 in immunity in association to the Insulin/insulin-like growth factor signalling (IIS) pathway.

| S-EPMC7827673 | biostudies-literature

Akirin Is Required for Muscle Function and Acts Through the TGF-? Sma/Mab Signaling Pathway in Caenorhabditis elegans Development.

Project description:Akirin, a conserved metazoan protein, functions in muscle development in flies and mice. However, this was only tested in the rodent and fly model systems. Akirin was shown to act with chromatin remodeling complexes in transcription and was established as a downstream target of the NF?B pathway. Here we show a role for Caenorhabditis elegans Akirin/AKIR-1 in the muscle and body length regulation through a different pathway. Akirin localizes to somatic tissues throughout the body of C. elegans, including muscle nuclei. In agreement with its role in other model systems, Akirin loss of function mutants exhibit defects in muscle development in the embryo, as well as defects in movement and maintenance of muscle integrity in the C. elegans adult. We also have determined that Akirin acts downstream of the TGF-? Sma/Mab signaling pathway in controlling body size. Moreover, we found that the loss of Akirin resulted in an increase in autophagy markers, similar to mutants in the TGF-? Sma/Mab signaling pathway. In contrast to what is known in rodent and fly models, C. elegans Akirin does not act with the SWI/SNF chromatin-remodeling complex, and is instead involved with the NuRD chromatin remodeling complex in both movement and regulation of body size. Our studies define a novel developmental role (body size) and a new pathway (TGF-? Sma/Mab) for Akirin function, and confirmed its evolutionarily conserved function in muscle development in a new organism.

| S-EPMC6945016 | biostudies-literature

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