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Mitochondria-selective primate cell fusions reveal functional consequences of mitochondrial divergence

ABSTRACT: Mitochondria-selective primate cell fusions reveal functional consequences of mitochondrial divergence

PROVIDER: PRJNA1124971 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29441170_1.fastq.gz	Fastqsanger.gz
	SRR29441170_2.fastq.gz	Fastqsanger.gz
	SRR29441171_1.fastq.gz	Fastqsanger.gz
	SRR29441171_2.fastq.gz	Fastqsanger.gz
	SRR29441172_1.fastq.gz	Fastqsanger.gz

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Mitochondria-selective primate cell fusions reveal functional consequences of mitochondrial divergence

Project description:Interspecies composite cell lines (or hybrid cells) are powerful tools to study genomic divergence between species. However, to date, the only pluripotent composite lines to exist are between human and chimpanzee. In addition, while these human-chimp composite lines contain the nuclear genomes from both species, they only contain the mitochondrial genome from one: human. Here we describe the generation of multiple composite pluripotent stem cell (PSC) lines between human and all other species of great apes (chimpanzee [Pan troglodytes], bonobo [Pan paniscus], gorilla [Gorilla gorilla], and orangutan [Pongo abelii]). In addition, we utilized a strategy based on enforced mitophagy to generate human-great ape composite PSCs that contain either the human or the non-human primate (NHP) mitochondrial genomes.

2025-06-03 | GSE270085 | GEO

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Primate cell fusion disentangles gene regulatory divergence in neural development

Project description:Among primates, humans display a unique trajectory of development responsible for the many traits specific to our species. However, the inaccessibility of human and chimpanzee primary tissues has limited our ability to study human evolution. Comparative in vitro approaches using primate-derived induced pluripotent stem cells have begun to reveal species differences on the cellular and molecular levels. In particular, brain organoids have emerged as a promising platform to study primate neural development in vitro, although cross-species comparisons of organoids are complicated by differences in developmental timing and variability of differentiation. Here, we developed a new platform to address these limitations. We first generated a panel of tetraploid hybrid stem cells by fusing human and chimpanzee induced pluripotent stem cells. We next applied this approach to study species divergence in cerebral cortical development by differentiating them into neural organoids. We found that hybrid organoids provide a controlled system for disentangling cis- and trans-acting gene expression divergence across cell types and developmental stages, revealing a signature of selection on astrocyte-related genes. In addition, we identified an up-regulation of human somatostatin receptor 2 (SSTR2), which regulates neuronal calcium signaling and is associated with neuropsychiatric disorders. We discovered a human-specific response to modulation of SSTR2 function in cortical neurons, underscoring the potential of this unique platform to reveal the molecular basis of human evolution.

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Primate transcript and protein expression levels evolve under compensatory selection pressures

Project description:Variation in gene regulation is thought to have played an important role in the evolution of primates, and many studies have documented differences in mRNA expression levels across primate species. However, it is not yet known to what extent measurements of divergence in mRNA levels reflect divergence in protein expression levels, which are more directly tied to phenotypic differences. To address this question, we used high-resolution, quantitative mass spectrometry to collect thousands of protein expression measurements from human, chimpanzee, and rhesus macaque lymphoblastoid cell lines (LCLs). We also used RNA sequencing to collect transcript expression data from the same samples. Considering the two datasets jointly we found that there is much more inter-species divergence at the mRNA level than at the protein level. Remarkably, we found dozens of genes with significant expression differences between species at the mRNA level yet little or no difference in protein expression. Overall, our data suggest a much stronger evolutionary constraint on protein expression levels than on mRNA levels. We conclude that inter-species mRNA expression differences may often have limited functional consequences due to either buffering or compensatory changes in post-transcriptional or posttranslational regulation of proteins. Gene expression patterns were compared between human, chimpanzee, and rhesus macaque lymphoblastoid cell lines (5 individuals from each species) using RNA-Seq. These gene expression patterns were also compared to protein expression patterns based on mass-spec data, which are available separately (see publication for details).

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Project description:camelus dromedarius mitochondria

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