Biology subjects

Lourenco, R.

Publications and source records attributed to Lourenco, R..

6 recordsLinked to original sources

bioRxiv2024

Metabolic reprogramming regulates histone lactylation during zebrafish caudal fin regeneration

Tissue regeneration relies on precise molecular mechanisms controlling cell fate transitions, with cell metabolism emerging as a key regulator. Lactate-derived histone lactylation has recently been identified as an important epigenetic modification involved in the regulation of gene expression across various biological processes. In this study, we report an increase in global histone lactylation and H3K18Lac levels in the mesenchyme and osteoblasts of the zebrafish caudal fin, during the early stages of regeneration. Our findings demonstrate that this epigenetic modification is functionally regulated by increased lactate levels, while inhibition of glycolysis and lactate production significantly reduces histone lactylation. These results suggest that metabolic reprogramming, in response to caudal fin injury, regulates histone lactylation, potentially modulating gene expression essential for cell plasticity and proliferation. This study expands our understanding of how metabolic-epigenetic interactions influence regenerative processes, providing valuable insights for the development of novel therapeutic strategies to enhance tissue repair. Summary statementLactate-derived histone lactylation plays a role in the early stages of zebrafish caudal fin regeneration, coupling metabolic adaptation with tissue repair mechanisms, through epigenetic regulation.

developmental biology↗

bioRxiv2022

Zebrafish caudal fin amputation induces a metabolic switch necessary for cell identity transitions and cell cycle re-entry to support blastema formation and bone regeneration

Regeneration depends on the ability of mature cells at the injury site to respond to injury, generating tissue-specific progenitors that incorporate the blastema and proliferate to reconstitute the original organ architecture. The metabolic microenvironment has been tightly connected to cell function and identity during development and tumorigenesis. Yet, the link between metabolism and cell identity at the mechanistic level in a regenerative context remains unclear. The adult zebrafish caudal fin, and bone cells specifically, have been crucial for the understanding of mature cell contribution to tissue regeneration. Here, we use this model to explore the relevance of glucose metabolism for the cell fate transitions preceding new osteoblast formation and blastema assembly. We show that injury triggers a shift in the metabolic profile at early stages of regeneration, enhancing glycolysis at the expense of mitochondrial oxidation. This metabolic switch mediates transcriptional changes that make mature osteoblast amenable to be reprogramed into pre-osteoblasts and induces cell cycle re-entry and progression. Manipulation of the metabolic profile led to severe reduction of the pre-osteoblast pool, diminishing their capacity to generate new osteoblasts, and to a complete abrogation of blastema formation. Overall, our data indicate that metabolic alterations have a powerful instructive role in regulating genetic programs that dictate fate decisions and stimulate proliferation, thereby providing a deeper understanding on the mechanisms regulating blastema formation and bone regeneration.

developmental biology↗

bioRxiv2021

Genomic bases of insularity and ecological divergence in barn owls (Tyto alba) of the Canary Islands

Islands, and the particular organisms that populate them, have long fascinated biologists. Due to their isolation, islands offer unique opportunities to study the effect of neutral and adaptive mechanisms in determining genomic and phenotypical divergence. In the Canary Islands, an archipelago rich in endemics, the barn owl (Tyto alba) is thought to have diverged into a subspecies (T. a. gracilirostris) on the eastern islands, Fuerteventura and Lanzarote. Taking advantage of 40 whole-genomes and modern population genomics tools, we provide the first look at the origin and genetic makeup of barn owls of this archipelago. We show that the Canaries hold diverse, long-standing and monophyletic populations with a neat distinction of gene pools from the different islands. Using new method, less sensitive to structure than classical FST, to detect regions involved in local adaptation to the insular environment, we identified a haplotype-like region likely under positive selection in all Canaries individuals. Genes in this region suggest morphological adaptations to insularity. In the eastern islands, where the subspecies T. a. gracilirostris is present, genomic traces of selection pinpoint signs of locally adapted body proportions and blood pressure, consistent with the smaller size of this population living in a hot arid climate. In turn, genomic regions under selection in the western barn owls from Tenerife showed an enrichment in genes linked to hypoxia, a potential response to inhabiting a small island with a marked altitudinal gradient. Our results illustrate the interplay of neutral and adaptive forces in shaping divergence and early onset speciation.

evolutionary biology↗

bioRxiv2021

Landscape and climatic variations of the Quaternary shaped multiple secondary contacts among barn owls (Tyto alba) of the Western Palearctic

The combined actions of climatic variations and landscape barriers shape the history of natural populations. When organisms follow their shifting niches, obstacles in the landscape can lead to the splitting of populations, on which evolution will then act independently. When two such populations are reunited, secondary contact occurs in a broad range of admixture patterns, from narrow hybrid zones to the complete dissolution of lineages. A previous study suggested that barn owls colonized the Western Palearctic after the last glaciation in a ring-like fashion around the Mediterranean Sea, and conjectured an admixture zone in the Balkans. Here, we take advantage of whole-genome sequences of 94 individuals across the Western Palearctic to reveal the complex history of the species in the region using observational and modeling approaches. Even though our results confirm that two distinct lineages colonized the region, one in Europe and one in the Levant, they suggest that it predates the last glaciation and identify a narrow secondary contact zone between the two in Anatolia. Nonetheless, we also show that barn owls re-colonized Europe after the glaciation from two distinct glacial refugia: a western one in Iberia and an eastern one in Italy. Both glacial lineages now communicate via eastern Europe, in a wide and permeable contact zone. This complex history of populations enlightens the taxonomy of Tyto alba in the region, highlights the key role played by mountain ranges and large water bodies as barriers and illustrates the power of population genomics in uncovering intricate demographic patterns.

evolutionary biology↗

bioRxiv2021

Unexpected post-glacial colonisation route explains the white colour of barn owls (Tyto alba) from the British Isles

The climate fluctuations of the Quaternary shaped the movement of species in and out of glacial refugia. In Europe, the majority of species followed one of the described traditional postglacial recolonization routes from the southern peninsulas towards the north. Like most organisms, barn owls are assumed to have colonized the British Isles by crossing over Doggerland, a land bridge that connected Britain to northern Europe. However, while they are dark rufous in northern Europe, barn owls in the British Isles are conspicuously white, a contrast that could suggest selective forces are at play on the islands. However, analysis of known candidate genes involved in colouration found no signature of selection. Instead, using whole genome sequences and species distribution modelling, we found that owls colonised the British Isles soon after the last glaciation, directly from a white coloured refugium in the Iberian Peninsula, before colonising northern Europe. They would have followed a yet unknown post-glacial colonization route to the Isles over a westwards path of suitable habitat in now submerged land in the Bay of Biscay, thus not crossing Doggerland. As such, they inherited the white colour of their Iberian founders and maintained it through low gene flow with the mainland that prevents the import of rufous alleles. Thus, we contend that neutral processes likely explain this contrasting white colour compared to continental owls. With the barn owl being a top predator, we expect future research will show this unanticipated route was used by other species from its paleo community.

evolutionary biology↗

bioRxiv2019

Deconstructing the structural conservation of distantly related bacterial nucleoid-associated proteins using functional chimeras

Nucleoid-associated proteins (NAPs) are DNA-binding proteins critical for the organization and function of the bacterial chromosome. A subclass of NAPs, including Caulobacter crescentus GapR and Escherichia coli H-NS, preferentially bind AT-rich regions of the nucleoid, but phylogenetic groups that encode GapR rarely encode H-NS. Here, utilizing genetic, biochemical, and biophysical studies of GapR in light of a recent DNA-bound crystal structure of GapR (Guo et al, 2018), we show that although evolutionarily distant, GapR and H-NS possess two regions that are structurally and functionally conserved. These regions are involved in self-association and DNA-binding, even though the two proteins oligomerize and regulate transcription differently. Functional analysis of GapR and H-NS protein chimeras identified structural elements present in H-NS but absent in GapR that rationalize differences in transcriptional regulation. In addition, we identified a sequence element unique to GapR that enables assembly into its tetrameric state. Using fluid-atomic force microscopy, we showed that GapR is capable of bridging DNA molecules in vitro. Together, these results demonstrate that two distantly related NAPs utilize evolutionarily conserved structural elements to serve specialized cellular roles via distinct mechanisms.

molecular biology↗