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Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade (CRISPR_Screen)

ABSTRACT: Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade (CRISPR_Screen)

PROVIDER: PRJNA630237 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11684921_1.fastq.gz	Fastqsanger.gz
	SRR11684921_2.fastq.gz	Fastqsanger.gz
	SRR11684922_1.fastq.gz	Fastqsanger.gz
	SRR11684922_2.fastq.gz	Fastqsanger.gz
	SRR11684923_1.fastq.gz	Fastqsanger.gz

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Project description:Developmental mechanisms play an important role in determining the costs, limits, and evolutionary consequences of phenotypic plasticity. One issue central to these claims is the metaphor of developmental “decoupling,” where alternate morphs result from evolutionarily independent developmental pathways. We test this assumption through a microarray study that explores differences in gene expression between alternate morphs relative to differences between sexes, a classic example of developmental decoupling. We then examine whether morph-biased genes are less conserved, relative to morph-shared genes, as predicted if developmental decoupling relaxes pleiotropic constraints on divergence. We focus on the developing horns and brains of two species of horned beetles with spectacular sexual- and morph-dimorphism in the expression of horns and fighting behavior. We find that patterns of gene expression were as divergent between morphs as they were between sexes. However, overall patterns of gene expression were also highly correlated across morphs and sexes. Morph-biased genes were more evolutionarily divergent, suggesting a role of relaxed pleiotropic constraints or relaxed selection. Together these results suggest that alternate morphs are somewhat developmentally decoupled, and that this decoupling has significant evolutionary consequences. However, alternative morphs may not be as developmentally decoupled as sometimes assumed and such hypotheses of development should be revisited and refined. We compared gene expression in three focal epidermal tissues (head, prothorax, legs) relative to a "control" tissue (dorsal abdominal epidermis) without any outgrowths. We also surveyed gene expression in the brain, relative to ganglionic neural tissue. We compared such patterns of gene expression between two male morphs (horned, fighter and hornless, sneaker males) and between males and females. We focused our array analyses (N = 48 arrays) on Onthophagus taurus (the species for which the array was designed), but also ran 19 arrays on thoracic tissue of Onthophagus nigriventris, a species which expresses thoracic horns as adults (O. taurus expresses head horns). Finally, we included a small subset of arrays (N = 4) directly hybridizing head epidermis tissue of O. taurus male morphs to validate our overall estimates of morph-biased expression. For more detail, refer to Snell-Rood et al. 2010, Evolution.

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Therapeutic decoupling of MHC-I and PD-L1 expression increases the efficacy of immune checkpoint blockade (CRISPR_Screen)

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