Biology subjects

Tamplin, O. J.

Publications and source records attributed to Tamplin, O. J..

3 recordsLinked to original sources

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↗

bioRxiv2025

GABA produced by multiple bone marrow cell types regulates hematopoietic stem and progenitor cells

Hematopoietic stem and progenitor cells (HSPCs) maintain homeostasis of the blood system by balancing proliferation and differentiation. Many extrinsic signals in the bone marrow (BM) microenvironment that regulate this balance are still unknown. We report gamma aminobutyric acid (GABA) metabolite produced in the BM as a regulator of HSPCs. Deletion of the glutamate decarboxylase enzymes (Gad1/2) that produce GABA in either B lineages or endothelial cells (ECs) leads to a moderate reduction in BM GABA levels and HSPC number, suggesting both cell types are GABA sources. However, simultaneous blockade of GABA production from both hematopoietic cells and ECs resulted in a greater reduction of both GABA levels and HSPC numbers. Lower GABA levels in the BM altered the gene expression profile of HSPCs, with expression reduced for proliferation-associated genes and increased for B lineage genes. Our findings suggest GABA from multiple sources coordinates to regulate HSPC activity. HighlightsO_LIGABA is produced by B cells and endothelial cells in the bone marrow C_LIO_LILower GABA level in the bone marrow reduces HSPC proliferation C_LIO_LILower GABA level primes HSPCs to upregulate B cell differentiation programs C_LI eTOC blurbTamplin and colleagues functionally test production of GABA metabolite in the bone marrow microenvironment as a regulator of hematopoietic stem and progenitor cells. Conditional deletion of GAD enzymes in B cells and endothelial cells demonstrated both are sources of GABA. Lower GABA level primed HSPCs to reduce proliferation and upregulate B cell differentiation programs. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/651482v2_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1db5c9forg.highwire.dtl.DTLVardef@9dfadcorg.highwire.dtl.DTLVardef@1c0b939org.highwire.dtl.DTLVardef@1c08a9b_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2020

Defining the ultrastructure of the hematopoietic stem cell niche by correlative light and electron microscopy

The blood system is supported by hematopoietic stem and progenitor cells (HSPCs) found in a specialized microenvironment called the niche. Many different niche cell types support HSPCs, however how they interact and their ultrastructure has been difficult to define. Here we show that single endogenous HSPCs can be tracked by light microscopy, then identified by serial block-face scanning electron microscopy (SBEM) at multiscale levels. Using the zebrafish larval kidney marrow (KM) niche as a model, we followed single fluorescently-labeled HSPCs by light sheet microscopy, then confirmed their exact location in a 3D SBEM dataset. Our approach allowed us to identify dopamine beta-hydroxylase (dbh) positive ganglia cells as a previously uncharacterized functional cell type in the HSPC niche. By integrating multiple imaging modalities, we could resolve the ultrastructure of single rare cells deep in live tissue and define all contacts between an HSPC and its surrounding niche cell types.

developmental biology↗