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Abstract Different modes of non‐genetic inheritance are expected to affect population persistence in fluctuating environments. We here analyseCaenorhabditis elegansdensity‐independent per capita growth rate time series on 36 populations experiencing six controlled sequences of challenging oxygen level fluctuations across 60 generations, and parameterise competing models of non‐genetic inheritance in order to explain observed dynamics. Our analysis shows that phenotypic plasticity and anticipatory maternal effects are sufficient to explain growth rate dynamics, but that a carryover model where ‘epigenetic’ memory is imperfectly transmitted and might be reset at each generation is a better fit to the data. We further find that this epigenetic memory is asymmetric since it is kept for longer when populations are exposed to the more challenging environment. Our analysis suggests that population persistence in fluctuating environments depends on the non‐genetic inheritance of phenotypes whose expression is regulated across multiple generations.
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Overview of the Special Issue “Protein-Based Infection, Inheritance, and Memory”
The Special Issue “Protein-Based Infection, Inheritance, and Memory” includes a set of experimental and review papers covering different aspects of protein memory, infection, and inheritance [...]
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- Award ID(s):
- 1817976
- PAR ID:
- 10434040
- Date Published:
- Journal Name:
- International Journal of Molecular Sciences
- Volume:
- 24
- Issue:
- 14
- ISSN:
- 1422-0067
- Page Range / eLocation ID:
- 11280
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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The female reproductive tract (FRT) is the most common site of infection during HIV transmission to women, but viral remodeling complicates characterization of cells targeted for infection. Here, we report extensive phenotypic analyses of HIV-infected endometrial cells by CyTOF, and use a ‘nearest neighbor’ bioinformatics approach to trace cells to their original pre-infection phenotypes. Like in blood, HIV preferentially targets memory CD4+ T cells in the endometrium, but these cells exhibit unique phenotypes and sustain much higher levels of infection. Genital cell remodeling by HIV includes downregulating TCR complex components and modulating chemokine receptor expression to promote dissemination of infected cells to lymphoid follicles. HIV also upregulates the anti-apoptotic protein BIRC5, which when blocked promotes death of infected endometrial cells. These results suggest that HIV remodels genital T cells to prolong viability and promote viral dissemination and that interfering with these processes might reduce the likelihood of systemic viral spread.more » « less
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Abstract Quantifying the inheritance of regulatory networks among proteins during asymmetric cell division remains a challenge due to the complexity of these systems and the lack of robust mathematical definitions for inheritance. We propose a novel statistical framework called ODEinherit to measure how much a mother cell’s regulatory network explains its daughter’s trajectories, addressing this gap. Using time-lapse microscopy, we tracked the expression dynamics of six proteins across 85 dividingS. cerevisiaecells, observed over eight hours at 12-minute intervals. Our framework employs a two-step approach. First, we estimate an ordinary differential equation (ODE) system for each cell to characterize protein interactions, introducing novel adjustments for non-oscillatory time series and leveraging multi-cell data. Second, we assess inheritance by clustering cells based on cycling markers and quantifying how well a mother’s regulatory network predicts her daughter’s. Preliminary findings suggest stage-dependent differences in inheritance rates, paving the way for applications in cellular stress response and cell-fate prediction studies across generations.more » « less
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Interspecific hybridization is a common and effective strategy for producing disease resilient citrus cultivars, including those with tolerance to Huanglongbing (HLB) disease. Several HLB-tolerant cultivars have been developed through hybridization of mandarins (Citrus reticulata) with their wild relativePoncirus trifoliata. One such cultivar, ‘US-897’, exhibits robust tolerance to the bacteria causing HLB disease,Candidatus Liberibacter asiaticus(CLas). To explore the genetic architecture of the early transcriptional response toCandidatusLiberibacter asiaticus (CLas) infection in ‘US-897’, we performed transcriptomic analysis of the hybrid and its parents, ‘Cleopatra’ (C. reticulata) and ‘Flying Dragon’ (P. trifoliata). A haplotype-resolved genome for ‘US-897’ was generated using PacBio HiFi sequencing reads to support quantification of the expression of both theCitrus and Poncirusalleles. By profiling gene expression in this parent-offspring trio, we were able to determine the mode of inheritance for genes differentially expressed between parents (‘Cleopatra’ and ‘Flying Dragon’) and their interspecific hybrid (‘US-897’), with the majority genes exhibiting non-additive patterns of gene expression inheritance. Additionally, analysis of allele-specific expression in the hybrid ‘US-897’ revealed the contribution of cis- versus trans-acting regulatory variants on genes with additive and non-additive modes of inheritance. A strong correlation between differential expression between parents and allele-specific expression in ‘US-897’ suggests that cis-regulatory variation is a significant source of expression divergence between species. Finally, genes responsive to infection withCLas were identified to explore how gene regulation associated with tolerance to HLB was rewired betweenCitrusand its relativePoncirus.more » « less
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Abstract The mechanism surrounding chromosome inheritance during cell division has been well documented, however, organelle inheritance during mitosis is less understood. Recently, the endoplasmic reticulum (ER) has been shown to reorganize during mitosis, dividing asymmetrically in proneuronal cells prior to cell fate selection, indicating a programmed mechanism of inheritance. ER asymmetric partitioning in proneural cells relies on the highly conserved ER integral membrane protein, Jagunal (Jagn). Knockdown of Jagn in the compound Drosophila eye displays a pleotropic rough eye phenotype in 48% of the progeny. To identify genes involved in Jagn dependent ER partitioning pathway, we performed a dominant modifier screen of the 3rd chromosome for enhancers and suppressors of this Jagn-RNAi-induced rough eye phenotype. We screened through 181 deficiency lines covering the 3L and 3R chromosomes and identified 12 suppressors and 10 enhancers of the Jagn-RNAi phenotype. Based on the functions of the genes covered by the deficiencies, we identified genes that displayed a suppression or enhancement of the Jagn-RNAi phenotype. These include Division Abnormally Delayed (Dally), a heparan sulfate proteoglycan, the γ-secretase subunit Presenilin, and the ER resident protein Sec63. Based on our understanding of the function of these targets, there is a connection between Jagn and the Notch signaling pathway. Further studies will elucidate the role of Jagn and identified interactors within the mechanisms of ER partitioning during mitosis.more » « less
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/ijms241411280
