Biology subjects

Moreira, L. M.

Publications and source records attributed to Moreira, L. M..

3 recordsLinked to original sources

bioRxiv2026

Convergent genetic evolution within Burkholderia multivorans chronic infections correlates with lung function decline in cystic fibrosis patients

The patterns and pathways of pathogen adaptation during chronic infections can reveal the gateways microbes must unlock to colonize and persist. In chronic lung infections of cystic fibrosis (CF) patients, a longtime goal has been to anticipate disease outcome and to improve treatment. Understanding of these processes for Burkholderia multivorans, the most prevalent CF pathogen of the Burkholderia cepacia complex, is limited. We investigate the evolution of seven different strains recovered from chronic airway infections of eight CF patients over 7-17 years. Despite divergent origins, each infecting population followed similar phylogenetic patterns of early diversification followed by the emergence of a dominant clade. The defining mutations of these prevalent lineages also affected the same set of global regulators, which altered clinically significant bacterial phenotypes in parallel directions. Mutated genes govern lipid metabolism, immune evasion, antibiotic resistance, biofilm production, and survival under oxygen limitation, and unite studies of chronic infections by different species of the B. cepacia complex. Most significantly, the phylodynamic signal that a dominant lineage had emerged within the infection, more so than any particular set of mutations, was associated with a more rapid decline in patient lung function. These findings reveal the importance of combining data from pathogen and host to link bacterial adaptation to disease progression, and ultimately to identify paths to reinforce host defense.

microbiology↗

bioRxiv2026

Transcriptomic Analysis Identifies Transient Mesendodermal State and Lineage Divergence in Human Pluripotent Stem Cell Differentiation

Human pluripotent stem cells serve as a vital model for studying early human lineage specification, yet conventional assessments relying on endpoint canonical markers of the three germ layers may overlook transient intermediate states and broader cellular programs. Here we combined directed differentiation of human induced pluripotent stem cells toward neuroectodermal, cardiac mesodermal, and hepatic endodermal lineages with comparative transcriptomic profiling across timepoints. Our analyses revealed a transient primitive streak-like mesendodermal state shared by mesodermal and endodermal trajectories, followed by lineage-specific divergence characterized by distinct transcriptional, metabolic, proliferative, and chromatin remodeling dynamics. Notably, endodermal differentiation exhibited rapid definitive endoderm commitment with enriched oxidative metabolism, whereas cardiac mesoderm differentiation showed progressive transcriptional remodeling and cardiac progenitor activation. These findings demonstrate that comparative transcriptomics can resolve developmental intermediates and cellular-state dynamics during human germ layer specification, providing a framework for evaluating lineage commitment beyond endpoint canonical marker expression, and to inform strategies for optimizing or redirecting differentiation.

bioengineering↗

bioRxiv2021

Transcriptome profiling of human pluripotent stem cell-derived cerebellar organoids reveals fastercommitment under dynamic conditions

Human induced pluripotent stem cells (iPSCs) have great potential for disease modeling. However, generating iPSC-derived models to study brain diseases remains a challenge. In particular, the ability to recapitulate cerebellar development in vitro is still limited. We presented a reproducible and scalable production of cerebellar organoids by using the novel Vertical-Wheel single-use bioreactors, in which functional cerebellar neurons were obtained. Here, we evaluate the global gene expression profiles by RNA sequencing (RNA-seq) across cerebellar differentiation, demonstrating a faster cerebellar commitment in this novel dynamic differentiation protocol. Furthermore, transcriptomic profiles suggest a significant enrichment of extracellular matrix (ECM) in dynamic-derived cerebellar organoids, which can better mimic the neural microenvironment and support a consistent neuronal network. Thus, an efficient generation of organoids with cerebellar identity was achieved for the first time in a continuous process using a dynamic system without the need of organoids encapsulation in ECM-based hydrogels, allowing the possibility of large-scale production and application in high-throughput processes. The presence of factors that favors angiogenesis onset was also detected in dynamic condition, which can enhance functional maturation of cerebellar organoids. We anticipate that large-scale production of cerebellar organoids may help developing models for drug screening, toxicological tests and studying pathological pathways involved in cerebellar degeneration.

bioengineering↗