Biology subjects

Perder, B.

Publications and source records attributed to Perder, B..

5 recordsLinked to original sources

bioRxiv2026

Large-scale endoplasmic reticulum membrane solidification spatially organizes proteins under thermal or metabolic stress

Organelle homeostasis is a key determinant of cellular fitness, yet how cells remodel their membranes in response to environmental change remains unclear. Here, we identify a temperature- and lipid saturation-dependent transformation of endoplasmic reticulum membranes into giant, rigid, multilamellar tubes in cells and in vivo. These rods emerge from demixing of saturated lipids into solid-like domains - a previously unrecognised, large-scale endomembrane phase behaviour, fundamentally distinct from the transient liquid-ordered nanodomains of the plasma membrane. ER-tubulating reticulon-homology proteins are excluded from rods; their segregation drives progressive membrane flattening and ultimately multilayered wrapping. Surfactant-producing alveolar type-II lung cells, enriched in saturated lipids, form rods even at 37{degrees}C, demonstrating that native lipid metabolism can induce this transformation. This spatially organizing lipid-protein domain interplay may tune the ER tubule/sheet balance and provide a homeoviscous mechanism to preserve fluidity in the cholesterol-poor ER under thermal or metabolic stress.

cell biology↗

bioRxiv2026

Hypoxia-activated scleraxis a mediates epicardial progenitor differentiation into a unique cardiac perivascular cell type

The epicardium is a crucial source of progenitor cells and paracrine signals that support heart development and regeneration. However, the molecular mechanisms that guide epicardial cell fate decisions remain incompletely understood. Here, we identify the transcription factor Scleraxis a (encoded by scxa) as a key regulator of epicardial progenitor differentiation in zebrafish. Through single-cell transcriptomics, genetic lineage tracing, and cardiac injury models, we show that scxa is transiently induced in activated epicardial progenitor cells (aEPCs) during both heart regeneration and developmental coronary angiogenesis. scxa+ epicardial cells primarily give rise to a previously uncharacterized cardiac population of perivascular cells marked by col18a1a, molecularly distinct from classical pericytes and vascular smooth muscle cells. We refer to this population as epicardial-derived perivascular mesenchymal cells (Epi-PMCs). These Epi-PMCs closely associate with coronary vessels and may contribute to vascular stabilization and remodeling, potentially through the anti-angiogenic but vessel-stabilizing activity of endostatin derived from collagen XVIII. Loss of scxa increases coronary vessel density. Mechanistically, we identify hypoxia and Hif1a signaling as upstream regulators of scxa, with systemic hypoxia or Hif factor stabilization robustly inducing scxa expression in the epicardium. Together, these findings uncover a hypoxia-responsive Scxa-Col18a1a axis that drives epicardial differentiation toward a vascular-supportive fate, offering new insight into the regulation of coronary vessel development and the regenerative potential of the epicardium.

developmental biology↗

bioRxiv2025

Zebrafish otic vesicle and mouse epididymis as model systems for studying columnar epithelial cell division

Epithelial cell division maintains tissue architecture through coordinated nuclear migration, cell shape changes, and spindle orientation. In columnar epithelia, interkinetic nuclear migration (INM) involves apical nuclear translocation in G2 phase and basal return post-mitosis, yet its regulation remains incompletely understood in vertebrates, in part due to limited in vivo live-imaging models. In this methodological study, we adapted the zebrafish embryonic otic vesicle as an in vivo model to investigate cell division dynamics in simple columnar epithelium using high-resolution live imaging and genetic tools. We demonstrated that apical INM initiates in mid-to-late G2 and is driven by dynein, not myosin II. Mitotic rounding is achieved via actomyosin-mediated basolateral constriction while maintaining basal attachment. Inhibiting myosin II impairs rounding and planar division, causing apical retention of daughter cells, suggesting planar division ensures proper integration. We additionally analyzed the mouse epididymal epithelium, a simple columnar epithelial tissue, to allow cross-species comparison of nuclear migration dynamics. Together, these optimized in vivo vertebrate models uncover conserved and tissue-specific mechanisms underlying epithelial organization and function, and importantly, provide tools for deeper mechanistic dissection in the future.

cell biology↗

bioRxiv2023

Cross-species single-cell comparison of systemic and cardiac inflammatory responses after cardiac injury

The immune system coordinates the response to cardiac injury and is known to control regenerative and fibrotic scar outcomes in the heart and subsequent chronic low-grade inflammation associated with heart failure. Here we profiled the inflammatory response to heart injury using single cell transcriptomics to compare and contrast two experimental models with disparate outcomes. We used adult mice, which like humans lack the ability to fully recover and zebrafish which spontaneously regenerate after heart injury. The extracardiac reaction to cardiomyocyte necrosis was also interrogated to assess the specific peripheral tissue and immune cell reaction to chronic stress. Cardiac macrophages are known to play a critical role in determining tissue homeostasis by healing versus scarring. We identified distinct transcriptional clusters of monocytes/macrophages in each species and found analogous pairs in zebrafish and mice. However, the reaction to myocardial injury was largely disparate between mice and zebrafish. The dichotomous response to heart damage between the mammalian and zebrafish monocytes/macrophages may underlie the impaired regenerative process in mice, representing a future therapeutic target.

cell biology↗

bioRxiv2022

Activation of an injury-associated transient progenitor state in the epicardium is required for zebrafish heart regeneration

The epicardium, a mesothelial cell tissue that encompasses vertebrate hearts, supports heart regeneration after injury through paracrine effects and as a source of multipotent progenitors. However, the progenitor state in the adult epicardium has yet to be defined. Through single-cell RNA-sequencing of isolated epicardial cells from uninjured and regenerating adult zebrafish hearts, we defined the epithelial and mesenchymal subsets of the epicardium. We further identified a transiently activated epicardial progenitor cell (aEPC) subpopulation marked by ptx3a and col12a1b expression. Upon cardiac injury, aEPCs emerge from the epithelial epicardium, migrate to enclose the wound, undergo epithelial-mesenchymal transition (EMT), and differentiate into mural cells and pdgfra+hapln1a+ mesenchymal epicardial cells. These EMT and differentiation processes are regulated by the Tgf{beta} pathway. Conditional ablation of aEPCs blocked heart regeneration through reduced Nrg1 expression and mesenchymal cell number. Our findings identify a transient progenitor population of the adult epicardium that is indispensable for heart regeneration and highlight it as a potential target for enhancing cardiac repair.

developmental biology↗