Biology subjects

Barbiero, S.

Publications and source records attributed to Barbiero, S..

4 recordsLinked to original sources

bioRxiv2025

Cell heterogeneity and fate bistability drive tissue patterning during intestinal regeneration

Tissue regeneration relies on the ability of cells to undergo de novo patterning. While tissue patterning has been viewed as the transition from initially identical un-patterned cells to an arrangement of different cell types, recent evidence suggests that initial heterogeneities between cells modulate tissue-scale pattern formation. Yet, how such heterogeneities arise and, thereafter, regulate cell type emergence in a population of cells is poorly understood. Using in vivo and in vitro mouse regenerative systems, we identify a critical tissue density that is required to induce heterogeneous inactivation of the mechanosensor YAP1. Experimental and biophysical approaches demonstrate that YAP1 cell-to-cell heterogeneity pre-patterns the first cell fate decision, via both chromatin remodelling and a supracellular feedback between FOXA1 and Delta-Notch signalling. This feedback motif induces cell fate bistability endowing memory to the system and the maintenance of patterns during homeostasis. These findings reveal a generalisable framework in which transient cell-to-cell heterogeneity, regulated by tissue-scale properties, serves as a critical control parameter for the emergence of cell fate and stable patterning during regeneration.

cell biology↗

bioRxiv2023

Dynamics and plasticity of stem cells in the regenerating human colonic epithelium

The human intestinal epithelium is a tissue with rapid turnover. Its complex regenerative process and differentiation trajectories have been challenging to study due to its inaccessibility and lack of temporal sampling. To this end, we developed a workflow to culture adult stem cell-derived human intestinal organoids from single cells to maturation. Extensive characterization of our model system indicated a transient regenerative response, followed by differentiation into all mature cell lineages. This switch is accompanied by a transition between two stem cell states. High-content screening and comparison to in vivo studies revealed that an initial fetal-like state is crucial for achieving successful regeneration, while the subsequent adult-like state is vital for maintaining a balance of cell lineages and continuous support of crypt-morphogenesis. Taken together, this study highlights the extensive plasticity of the intestinal epithelium and paves the way for further studies of human intestinal regeneration and its deregulation in pathologies.

cell biology↗

bioRxiv2023

An integrated transcriptomic cell atlas of human endoderm-derived organoids

Human stem cells can generate complex, multicellular epithelial tissues of endodermal origin in vitro that recapitulate aspects of developing and adult human physiology. These tissues, also called organoids, can be derived from pluripotent stem cells or tissue-resident fetal and adult stem cells. However, it has remained difficult to understand the precision and accuracy of organoid cell states through comparison with primary counterparts, and to comprehensively assess the similarity and differences between organoid protocols. Advances in computational single-cell biology now allow the integration of datasets with high technical variability. Here, we integrate single-cell transcriptomes from 218 samples covering organoids of diverse endoderm-derived tissues including lung, pancreas, intestine, liver, biliary system, stomach, and prostate to establish an initial version of a human endoderm organoid cell atlas (HEOCA). The integration includes nearly one million cells across diverse conditions, data sources and protocols. We align and compare cell types and states between organoid models, and harmonize cell type annotations by mapping the atlas to primary tissue counterparts. To demonstrate utility of the atlas, we focus on intestine and lung, and clarify ontogenic cell states that can be modeled in vitro. We further provide examples of mapping novel data from new organoid protocols to expand the atlas, and showcase how integrating organoid models of disease into the HEOCA identifies altered cell proportions and states between healthy and disease conditions. The atlas makes diverse datasets centrally available, and will be valuable to assess organoid fidelity, characterize perturbed and diseased states, and streamline protocol development.

cell biology↗

bioRxiv2020

Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology

Between 6-20% of the cellular proteome is under circadian control to tune cell function with cycles of environmental change. For cell viability, and to maintain volume within narrow limits, the osmotic pressure exerted by changes in the soluble proteome must be compensated. The mechanisms and consequences underlying compensation are not known. Here, we show in cultured mammalian cells and in vivo that compensation requires electroneutral active transport of Na+, K+, and Cl- through differential activity of SLC12A family cotransporters. In cardiomyocytes ex vivo and in vivo, compensatory ion fluxes alter their electrical activity at different times of the day. Perturbation of soluble protein abundance has commensurate effects on ion composition and cellular function across the circadian cycle. Thus, circadian regulation of the proteome impacts ion homeostasis with substantial consequences for the physiology of electrically active cells such as cardiomyocytes.

cell biology↗