Biology subjects

Giselbrecht, S.

Publications and source records attributed to Giselbrecht, S..

4 recordsLinked to original sources

bioRxiv2026

Sex-differentiated hormonal microenvironments recapitulate in vivo liver metabolism in human iPSC-derived organoids

Bioengineers strive to recreate in vivo microenvironments in vitro to reduce our use of animal models and provide insights into human biology. While liver models show promise, sex differences in liver biology remain largely neglected in preclinical studies. Despite the 2014 EU mandate for the inclusion of women in clinical trials, decoupling of research data by sex is historically rare, with only 11% of papers disaggregating data by sex. This gap contributes to women being more susceptible to drug-induced liver injury (DILI) and being underserved in drug development, as well as to costly drug attrition levels. Here we present a novel approach to modelling sex differences in vitro. Human induced pluripotent stem cells (iPSCs) from both male (XY) and female (XX) donors, were differentiated into hepatocyte liver spheroids and exposed to in vivo-mimicking levels of testosterone, progesterone, and oestrogen in high-throughput microwell format. We successfully recapitulated sex-specific metabolic profiles and demonstrated significant differences in CYP1A2 and CYP3A4 drug metabolism and gene expression patterns consistent with reported in vivo observations, without compromising cell viability. These findings validate the utility of sex-differentiated microenvironments in early-stage research, offering a pathway to refine animal and clinical trials and improve therapeutic outcomes for all sexes.

cell biology↗

bioRxiv2026

Microphysiological Flow Batteries For Dynamic EDC Screening Of mESC-derived Thyroid Organoids

Endocrine disrupting chemicals (EDCs) are ubiquitous environmental contaminants capable of dysregulating the production of thyroid hormones. Traditional thyroid toxicological assays rely on 2D cell cultures and animal models, both of which fail to accurately recapitulate human thyroid physiology and provide limited mechanistic insight into EDC toxicity. To overcome these limitations, we report a novel thyroid-on-chip platform integrating mouse embryonic stem cell-derived thyroid organoids with advanced organ-on-chip (OoC) technology and downstream multi-omics analysis. The platform leverages a reversibly-sealed microphysiological flow battery (MFB) to allow scale up of dynamic organoid culture and controlled chemical exposure while reducing operational complexity. Upon EDC exposure, transcriptomic and proteomic analysis revealed new molecular signatures of thyroid disruption across four different EDC classes, even at very low EDC concentrations (1nM), validating the capacity of this system to mechanistically dissect EDC-induced responses. This represents an integrated platform consists of an advanced physiologically relevant assay framework for next-generation endocrine toxicity testing, bridging the gap between in vitro screening and in vivo thyroid physiology.

bioengineering↗

bioRxiv2026

Microfluidic bioprinting of a physiologically relevant thyroid three-dimensional in vitro model

Endocrine disruptors (EDs) are an exogenous group of compounds associated with thyroid malfunctioning in the human body. Nonetheless, there are currently no adequate in vivo or in vitro models for the preclinical testing of these compounds since both animal and two-dimensional (2D) cell-based models are not able to mimic thyroid physiological conditions from both functional and three-dimensional (3D) organization perspective. Recently, bioprinting technologies emerged as an innovative tool in the field of regenerative medicine and advanced 3D in vitro models that allow the creation of 3D well-organized structures able to mirror physiologically relevant tissue and organ architectures. In this study, we evaluated microfluidic bioprinting as a biofabrication technology to develop a 3D in vitro model of the thyroid gland. We studied the fundamental parameters to obtain a fine control over the bioprinted fibres for different biomaterials. Then, we assessed the possibility to bioprint single thyroid cells, thyroid spheroids and finally mouse embryonic stem cell-derived thyroid follicles. The different cell types maintained high viability and metabolic activity. The bioprinted thyroid model showed high expression of different early and late functional markers and to be responsive to ED exposure. These bioprinted thyroid constructs could provide a new set of advanced 3D in vitro models to test potential EDs and possible adverse outcomes that may be associated with their administration or exposure.

bioengineering↗

bioRxiv2026

A dual role for CTCF in development

CTCF is an essential DNA binding protein whose absence leads to embryonic lethality. CTCF is primarily known for its role in 3D genome organization where its N-terminal domain interacts with cohesin to anchor chromatin loops. How CTCF facilitates proper embryonic development remains unclear, necessitating temporal control to resolve its stage-specific functions. By combining gastruloids, an in vitro model of embryonic development, with a degron system to rapidly deplete CTCF at defined timepoints, we show that early CTCF depletion impairs early gastruloid morphogenesis. Surprisingly, ATAC-seq and time-resolved RNA-seq revealed that differentiation was unaffected. CTCF binding is strongly enriched at promoters of downregulated genes. Re-expression of a CTCF variant with an N-terminal truncation, incapable of looping, was sufficient to rescue the expression of CTCF-promoter bound genes and the defects in morphogenesis. However, extended culture (up to 168 hours) of gastruloids reconstituted with N-terminal truncated CTCF led to their collapse. Our work shows that CTCF has a dual function in early mammalian development: at early stages CTCF regulates developmentally important genes through promoter binding, while at later stages its looping function is required for correct development. HighlightsO_LICTCF is essential for gastruloid morphogenesis but dispensable for cell differentiation C_LIO_LICTCF activates genes through promoter binding C_LIO_LICTCF promoter target regulation drives in vitro gastrulation C_LIO_LIPost-gastrulation development in vitro is driven by CTCFs looping function C_LI

genomics↗