Biology subjects

Liao, C.-W.

Publications and source records attributed to Liao, C.-W..

4 recordsLinked to original sources

bioRxiv2025

An early evolutionary stage of mutualistic endosymbiosis reveals a parasitic aspect of endosymbionts

Mutualistic endosymbiosis is a cornerstone of evolutionary innovation, enabling organisms to exploit diverse niches unavailable to individual species. However, our knowledge about the early evolutionary stage of this relationship remains limited. The association between the ciliate Tetrahymena utriculariae and its algal endosymbiont Micractinium tetrahymenae indicates an incipient stage of endosymbiosis. Although T. utriculariae cells rely on endosymbiotic algae to grow in low-oxygen conditions, they gradually lose the endosymbionts in aerobic conditions. Our comparative genomics reveals that the mitochondria-related genes of T. utriculariae are fast-evolving. Symbiotic cells display elongated mitochondria, which interact intimately with endosymbionts. Moreover, inhibiting mitochondrial fatty acid oxidation reduces host fitness but increases the endosymbiont population. Time-series transcriptomics reveal physiological fine-tuning of the host during day and night, underscoring adaptations for nutrient exchange and regulation. Notably, endosymbiotic algae downregulate photosynthesis-related genes compared with free-living cells, correlated with a substantially reduced chlorophyll content. These findings indicate that the endosymbionts exploit host metabolites to supplement reduced photosynthesis. Consistently, symbiotic Tetrahymena cells exhibit lower fitness under aerobic conditions than aposymbiotic cells. Our results support that mutualistic and parasitic relationships between symbiotic organisms are condition-dependent, especially at an early evolutionary stage.

evolutionary biology↗

bioRxiv2024

Intraplacental injection of human iPSC-derived PDX1+ pancreatic progenitors prolongs Pdx1-deficient mice survival

Interspecies chimeras comprising human tissues have potential for use in disease modeling and regenerative medicine. Here, we successfully transplanted human induced pluripotent stem cell (iPSC)-derived PDX1+ pancreatic progenitor cells into Pdx1-deficient mouse embryos via intraplacental injection. The engrafted human cells predominantly localized to the duodenum, produced insulin, and extended the lifespan of Pdx1-/- mice by up to 10 days after birth. Transcriptomic analyses confirmed human pancreatic gene expression in human cells engrafted into the mouse duodenum. Our findings demonstrated the feasibility of generating interspecies chimeras with functional human pancreatic cells through in utero transplantation of lineage-committed progenitors. This approach circumvents developmental barriers while minimizing ethical concerns associated with PSCs. However, the incomplete rescue of the Pdx1-/- phenotype highlights the need for further research to enhance human cell engraftment and tissue integration. Overall, this study provides a foundation for developing human-animal chimera models for studying human development and regenerative therapies.

cell biology↗

bioRxiv2022

Rapid compensatory evolution by secondary perturbation of a primary disrupted transcriptional network

The discrete steps of transcriptional rewiring have been proposed to occur neutrally to ensure steady gene expression under stabilizing selection over long time-scales, especially when a regulon is being transferred from one transcription factor (TF) to another. Cooperative DNA binding between redundant regulatory components at the intermediate transition stage is believed to mediate this process, enabling a conflict-free switch between two TFs without a disruptive change in gene expression. Here, we have performed an evolutionary repair experiment on the Lachancea kluyveri yeast sef1{Delta} mutant by means of a suppressor development strategy. Complete loss of SEF1 forced cells to activate a rewiring process to compensate for the pleiotropic defects arising from misexpression of multiple TCA cycle genes. Using different selective conditions, we identified one generalist and one specialist suppressive loss-of-function mutation of IRA1 and AZF1, respectively. Our subsequent analyses show that Azf1 is a weak transcriptional activator regulated by the Ras1-PKA pathway. Azf1 loss-of-function triggers extensive gene expression changes responsible for both the compensatory and trade-off phenotypes. Our results indicate that the pleiotropic effects of dual perturbation of transcriptional networks are a potential mechanism for rapid adaptive compensation, facilitating the process of incipient transcriptional rewiring, and formation of complex traits.

evolutionary biology↗

bioRxiv2020

Differential Hsp90-dependent gene expression is strain-specific and common among yeast strains

Enhanced phenotypic diversity increases the likelihood of a population surviving catastrophic conditions. It has been suggested that Hsp90, an essential molecular chaperone in eukaryotes, can suppress (i.e., buffer) or enhance (i.e., potentiate) the effects of genetic variation, enabling organisms to adjust their levels of phenotypic diversity in response to environmental cues. Many Hsp90-interacting proteins are involved in signaling transduction pathways and transcriptional regulation. However, it remains unclear if Hsp90-dependent differential gene expression is common in natural populations. By examining the gene expression profiles of five diverse yeast strains, we identified many genes exhibiting Hsp90-dependent strain-specific differential expression. We employed an analysis pipeline to identify transcription factors (TFs) potentially contributing to variable expression. We found that upon Hsp90 inhibition or heat stress, activities or abundances of Hsp90-dependent TFs varied among strains, resulting in differential strain-specific expression of their target genes, which consequently led to phenotypic diversity. We provide evidence that individual populations can readily display specific Hsp90-dependent gene expression, suggesting that the evolutionary impacts of Hsp90 are widespread in nature. HighlightsO_LIHsp90-dependent gene expression varies among different yeast strains. C_LIO_LIHsp90 differentially influences transcriptional activity or protein abundances of transcription factors among yeast strains. C_LIO_LIDifferential strain-specific gene expression is correlated with phenotypic variations upon Hsp90 inhibition. C_LIO_LIHsp90-mediated strain-specific regulation manifests under environmental stress. C_LI

evolutionary biology↗