Biology subjects

Lambiase, G.

Publications and source records attributed to Lambiase, G..

3 recordsLinked to original sources

bioRxiv2025

A Conserved Venous Remodeling Program Governs Inferior Vena Cava Formation in Zebrafish

The Inferior Vena Cava (IVC), the largest venous conduit in mammals, forms through complex remodeling of the embryonic cardinal veins (CVs), a process prone to congenital anomalies, with significant clinical implications. However, the mechanisms underlying IVC formation remain unclear. Here, we identify a conserved IVC in zebrafish that emerges during metamorphosis through remodeling of the embryonic CVs, mirroring the mammalian process. Using in vivo imaging and clonal lineage tracing, we identify the cellular origins and molecular mechanisms controlling IVC formation and demonstrate that the transition from CV to IVC represents a shift from a multifunctional embryonic vein to a specialized adult conduit adapted for high-volume blood return. Overall, our findings illuminate conserved mechanisms of venous remodeling and establish a foundation for investigating congenital venous anomalies.

developmental biology↗

bioRxiv2024

Identification of Cellular Signatures Associated with Chinese Hamster Ovary (CHO) Cell Adaptation for Secretion of Antibodies

The secretory capacity of Chinese hamster ovary (CHO) cells remains a fundamental bottleneck in the manufacturing of protein-based therapeutics. Unconventional biological drugs with complex structures and processing requirements are particularly problematic. Although engineered vector DNA elements can achieve rapid and high-level therapeutic protein production, a high metabolic and protein folding burden is imposed on the host cell. Cellular adaptations to these conditions include differential gene expression profiles that can in turn influence the productivity and quality control of recombinant proteins. In this study, we used quantitative transcriptomics and proteomics analyses to investigate how biological pathways change with antibody titre. Gene and protein expression profiles of CHO pools and clones producing a panel of different monoclonal and bispecific antibodies were analysed during fed-batch production. Antibody-expressing CHO pools were heterogeneous, resulting in few discernible genetic signatures. Clonal lines derived from these pools, selected for high and low production, yielded a small number of differentially expressed proteins that correlated with productivity and were shared across biotherapeutics. However, the dominant feature associated with higher protein production was transgene copy number and resulting mRNA expression level. Moreover, variability between clones suggested that the process of cellular adaptation is variable with diverse cellular changes associated with individual adaptation events.

bioengineering↗

bioRxiv2021

Generation of specialized blood vessels through transdifferentiation of lymphatic endothelial cells

The lineage and developmental trajectory of a cell are key determinants of cellular identity. Yet, the functional relevance of deriving a specific cell type from ontologically distinct progenitors, remains an open question. In the case of the vascular system, blood and lymphatic vessels are composed of endothelial cells (ECs) that differentiate and diversify to cater the different physiological demands of each organ. While lymphatic vessels have been shown to originate from multiple cell sources, lymphatic ECs (LECs) themselves seem to have a unipotent cell fate. In this work we uncover a novel mechanism of blood vessel formation through transdifferentiation of LECs. Using advanced long-term reiterative imaging and lineage-tracing of ECs in zebrafish, from embryonic development through adulthood, we reveal a hitherto unknown process of LEC-to-BEC transdifferentiation, underlying vascularization of the anal fin (AF). Moreover, we demonstrate distinct functional implications for deriving AF vessels from either LECs or BECs, uncovering for the first time a clear link between cell ontogeny and functionality. Molecularly, we identify Sox17 as a negative regulator of lymphatic fate specification, whose specific expression in AF LECs suppresses its lymphatic cell fate. Finally, we show that akin to the developmental process, during adult AF regeneration the vasculature is re-derived from lymphatics, demonstrating that LECs in the mature fish retain both potency and plasticity for generating specialized blood vessels. Overall, our work highlights a novel mechanism of blood vessel formation through LEC trans-differentiation, and provides the first in vivo evidence for a link between cell ontogeny and functionality in ECs.

developmental biology↗