Generation and characterization of inducible KRAB-dCas9 iPSCs from primates for cross-species CRISPRi

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 110090 - 110090

Published: May 23, 2024

Comparisons of molecular phenotypes across primates provide unique information to understand human biology and evolution, single-cell RNA-seq CRISPR interference (CRISPRi) screens are a powerful approach analyze them. Here, we generate validate three human, gorilla, two cynomolgus iPS cell lines that carry dox-inducible KRAB-dCas9 construct at the AAVS1 locus. We show despite variable expression levels among lines, comparable downregulation target genes phenotypic effects observed in CRISPRi screen. Hence, valuable resources for performing further extending non-human primates.

Language: Английский

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Using a comprehensive atlas and predictive models to reveal the complexity and evolution of brain-active regulatory elements

Science Advances, Journal Year: 2024, Volume and Issue: 10(21)

Published: May 23, 2024

Most genetic variants associated with psychiatric disorders are located in noncoding regions of the genome. To investigate their functional implications, we integrate epigenetic data from PsychENCODE Consortium and other published sources to construct a comprehensive atlas candidate brain cis-regulatory elements. Using deep learning, model these elements' sequence syntax predict how binding sites for lineage-specific transcription factors contribute cell type-specific gene regulation various types glia neurons. The evolutionary history suggests that new regulatory information emerges primarily via smaller mutations within conserved mammalian elements rather than entirely human- or primate-specific sequences. However, elements, particularly those active during fetal development excitatory neurons astrocytes, implicated heritability brain-related human traits. Additionally, introduce PsychSCREEN, web-based platform offering interactive visualization PsychENCODE-generated diverse individuals healthy controls.

Language: Английский

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Chiropterans Are a Hotspot for Horizontal Transfer of DNA Transposons in Mammalia

Molecular Biology and Evolution, Journal Year: 2023, Volume and Issue: 40(5)

Published: April 18, 2023

Abstract Horizontal transfer of transposable elements (TEs) is an important mechanism contributing to genetic diversity and innovation. Bats (order Chiroptera) have repeatedly been shown experience horizontal TEs at what appears be a high rate compared with other mammals. We investigated the occurrence horizontally transferred (HT) DNA transposons involving bats. found over 200 putative HT within bats; 16 were shared across distantly related mammalian clades, 2 fish two lizard species. Our results indicate that bats are hotspot for transposons. These events broadly coincide diversification several bat supporting hypothesis transposon invasions contributed

Language: Английский

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Comparative genomics of monotremes provides insights into the early evolution of mammalian epidermal differentiation genes

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 16, 2024

Abstract The function of the skin as a barrier against environment depends on differentiation epidermal keratinocytes into highly resilient corneocytes that form outermost layer. Many genes encoding structural components are clustered in complex (EDC), which has been described placental and marsupial mammals well non-mammalian tetrapods. Here, we analyzed genomes platypus ( Ornithorhynchus anatinus ) echidna Tachyglossus aculeatus to determine gene composition EDC basal clade mammals, monotremes. We report mammal-specific subfamilies small proline-rich proteins (SPRRs) late cornified envelope single-copy such involucrin conserved monotremes, suggesting they have originated stem mammals. Monotremes at least one homologous group filaggrin FLG ), FLG2 hornerin HRNR but no clear one-to-one pairwise ortholog either , or . Caspase-14, keratinocyte differentiation-associated protease implicated processing filaggrin, is encoded by 3 copies echidna. Our results reveal evolutionarily clade-specific features genetic regulation

Language: Английский

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Genetic load and viability of a future restored northern white rhino population

Evolutionary Applications, Journal Year: 2024, Volume and Issue: 17(4)

Published: April 1, 2024

Abstract As biodiversity loss outpaces recovery, conservationists are increasingly turning to novel tools for preventing extinction, including cloning and in vitro gametogenesis of biobanked cells. However, restoration populations can be hindered by low genetic diversity deleterious load. The persistence the northern white rhino ( Ceratotherium simum cottoni ) now depends on cryopreserved cells 12 individuals. These banked genomes have higher than southern rhinos C. s. ), a sister subspecies that successfully recovered from severe bottleneck, but potential impact load is unknown. We estimated how demographic history has shaped genome‐wide nine 13 rhinos. bottleneck left with more fixed homozygous alleles longer runs homozygosity, whereas retained masked heterozygosity. To gauge fitness population restored cells, we simulated recovery using as benchmark viable population. Unlike traditional restoration, cell‐derived founders reintroduced subsequent generations boost lost relieve inbreeding. In simulations repeated reintroduction into population, cost remained lower borne Without reintroductions, rapid growth (>20–30% per generation) would needed maintain comparable fitness. Our results suggest inbreeding depression not necessarily barrier demonstrate relieves some constraints conventional limited founder pool. Established conservation methods protect healthy will remain paramount, emerging technologies hold promise bolster these combat extinction crisis.

Language: Английский

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