Biology subjects

Enkhbayar, K.

Publications and source records attributed to Enkhbayar, K..

4 recordsLinked to original sources

bioRxiv2026

The endothelial scavenger receptor stab2 is required for proper hematopoietic stem and progenitor cell development in the fetal blood stem cell niche

Hematopoietic stem and progenitor cell (HSPC) niches support lifelong production of blood and immune cells. Recently, we identified a gene signature unique to HSPC niche endothelial cells that is highly conserved across species and developmental time and includes the scavenger receptors stab1/2 and mrc1a. Whether these receptors support HSPC development remains unclear. To investigate this, we used chemical inhibition and CRISPR mutagenesis in zebrafish and found that loss of stab2, and to a lesser degree stab1, reduced the number of embryonic runx1(+) HSPCs. Subsequent analyses of an additional HSPC marker (cd41) revealed an imbalance in the HSPC pool in stab2 mutants, with reductions in runx1(+)cd41(+) and runx1(+)cd41(-) sub-populations containing stem cells and erythroid progenitors, respectively, the latter of which was most decreased. Our findings suggest stabilin scavenger receptors support HSPC development in the fetal niche, which could inform clinical strategies for culturing and expanding HSPCs.

developmental biology↗

bioRxiv2026

TP53-mediated bidirectional lineage plasticity drives alveolar epithelial cell extrusion and tissue remodeling

Cell extrusion contributes to epithelial homeostasis, but its dysregulation can lead to tumorigenesis or degeneration. A fine balance in this process is therefore essential for tissue integrity. Yet the cell types and states vulnerable to extrusion, and the mechanisms that drive it, remain elusive. Here, using spatial maps of cell states in human idiopathic pulmonary fibrosis (IPF) we find that aberrant TP53 activation in alveolar epithelial cells drives cell extrusion. Genetic modulation of TP53 specifically in alveolar epithelial type 1 cells (AT1) was sufficient to induce plasticity and subsequent extrusion as demonstrated by lineage tracing and live imaging. Strikingly, single cell and bulk transcriptome profiling revealed aberrant TP53 drives AT1 cells to acquire a transitional state mirroring AT2-derived regeneration associated intermediate states. Critically, loss of AT1 derived transitional state triggers a compensatory AT2-derived regenerative response, establishing a bidirectional transitional state that activates myofibroblasts and remodels the alveolus. Together, our study implicates AT1 plasticity and their reversion as an unrecognized driver of epithelial cell loss and establishes bidirectional transitional state as a central mechanism underlying progression of fibrotic remodeling.

Cell Biology↗

bioRxiv2025

Vcam1 in endothelial and stromal cells regulates hematopoietic stem cell contact with the niche

Hematopoietic stem and progenitor cells (HSPCs) are essential for differentiation into all blood cell types. In mammals, the interaction between HSPCs and the fetal liver niche during development is critical for stem cell maturation. Integrin alpha 4 (Itga4) on HSPCs and vascular cell adhesion molecule (Vcam1) on niche cells are critical for HSPC colonization of the fetal liver (FL). Itga4 and Vcam1 also function in the zebrafish equivalent of the FL, the caudal hematopoietic tissue (CHT), however, the specific niche cells that express Vcam1 remain unclear. Using multiple approaches, including fluorescent in situ hybridization, we found Vcam1 is expressed in endothelial cells (ECs) and mesenchymal stromal cells (MSCs), but not macrophages. Time-lapse live imaging of itga4 mutants showed the Itga4-Vcam1 axis is required for HSPC retention in the CHT niche, but not homing or lodgment. Our results show that Itga4 on HSPCs and Vcam1 on ECs and MSCs are involved in retention in the CHT niche. SummaryBlood stem cell interaction with the niche microenvironment during development is critical for establishing a robust stem cell pool into adulthood. This study determines the niche cell types that present Vcam1 in the embryo and allow interaction with blood stem cells.

developmental biology↗

bioRxiv2021

Transcription factor induction of vascular blood stem cell niches in vivo

The hematopoietic niche is a supportive microenvironment comprised of distinct cell types, including specialized vascular endothelial cells that directly interact with hematopoietic stem and progenitor cells (HSPCs). The molecular factors that specify niche endothelial cells and orchestrate HSPC homeostasis remain largely unknown. Using multi-dimensional gene expression and chromatin accessibility analyses, we define a conserved gene expression signature and cis-regulatory landscape unique to sinusoidal endothelial cells in the HSPC niche. Using enhancer mutagenesis and transcription factor overexpression, we elucidate a transcriptional code involving members of the Ets, Sox and Nuclear Hormone Receptor families that is sufficient to induce ectopic niche endothelial cells that associate with mesenchymal stromal cells and support the recruitment, maintenance and division of HSPCs in vivo. These studies set forth an approach for generating synthetic HSPC niches, in vitro or in vivo, and for effective therapies to modulate the endogenous niche.

developmental biology↗