Biology subjects

Petentler, K.

Publications and source records attributed to Petentler, K..

3 recordsLinked to original sources

bioRxiv2026

In situ identification of pre-hematopoietic stem cells and their niche

Definitive hematopoietic stem cells (HSCs) emerge predominantly along the ventral surface of the dorsal aorta in the embryonic aorta-gonad-mesonephros (AGM) region, yet the spatial organization of the niche underlying this developmental asymmetry remains poorly understood. Defining the native niche of pre-HSCs has also been hindered by their rarity, transient nature and lack of a single definitive marker for their identification in situ. Here, we integrated single-cell and spatial transcriptomics to construct a spatiotemporal atlas of the niche in the AGM. Neural cells and chondrogenic mesenchyme predominated dorsally, whereas N-cadherin mesenchymal stromal cells (N-cad+ MSCs) formed a ventral layer between the aortic endothelium and mesonephric cells. BMP and SHH signaling showed overall dorsal enrichment, whereas WNT, NOTCH and KIT signaling were enriched ventrally, with these cellular and signaling patterns dynamically remodeled across HSC ontogeny. Imaging-based spatial transcriptomics validated the findings and further enabled the identification of individual pre-HSCs in situ and revealed a multicellular niche comprising endothelial cells, N-cad+ MSCs, intra-aortic hematopoietic cluster cells and macrophages. TGF{beta} and NOTCH signals were primarily supplied locally, whereas major sources of BMP and WNT were more distant. Functional perturbation identified niche-derived CD200 as an immune-regulatory signal promoting HSC development, validating a spatially predicted niche interaction. Together, our findings link tissue-scale spatial organization with the local multicellular niche supporting the preferential development of HSCs along the ventral aorta.

developmental biology↗

bioRxiv2026

Minicollagen expression dynamics reveal a transcriptional program for cnidogenesis in the sea anemone Nematostella vectensis

Cnidae are explosive harpoon-like organelles localized within stinging cells, or cnidocytes, of the phylum Cnidaria (jellyfish, hydroids, sea anemones, and corals). These unique Golgi-derived vesicular structures define the phylum and are prominent examples of an evolutionary cellular novelty. While recent studies have focused on the developmental specification and regulation of cnidocytes more broadly, less is understood about gene expression patterns, structural variations, and toxin repertoires within distinct cnidae subtypes. Here, we determine the transcriptional profile of two major cnidae subtypes in the sea anemone Nematostella vectensis, nematocytes and spirocytes, using the cnidae-specific structural family of proteins called minicollagens. We first define the in vivo expression patterns for three known and three uncharacterized minicollagen orthologs. We show that four minicollagens are broadly expressed throughout ectodermal cnidocytes in developing larvae and primary polyps while two others are restricted to tentacular cnidocytes. Leveraging whole adult scRNA-seq data and two novel transgenic reporter lines, we then demonstrate that the tentacle-restricted cnidocytes are developing spirocytes that are distinguished by expression of the minicollagen NvNcol5. To deepen our analysis of cnidocyte gene expression, we used a customized RNA-FACS-seq pipeline to determine global transcriptional differences between these two subtypes. This approach identified a suite of differentially expressed genes, illuminating spatial and temporal gene expression dynamics across both developing nematocytes and spirocytes. Altogether, our experiments provide fundamental and novel insights into the specialization of cnidarian stinging cells while establishing a rich set of resources for further investigation.

evolutionary biology↗

bioRxiv2024

Characterization of Multicellular Niches Supporting Hematopoietic Stem Cells Within Distinct Zones

Previous studies of hematopoietic stem cells (HSCs) primarily focused on single cell-based niche models, yielding fruitful but conflicting findings1-5. Here we report our investigation on the fetal liver (FL) as the primary fetal hematopoietic site using spatial transcriptomics. Our study reveals two distinct niches: the portal-vessel (PV) niche and the sinusoidal niche. The PV niche, composing N-cadherin (N-cad)HiPdgfr+ mesenchymal stromal cells (MSCs), endothelial cells (ECs), and N-cadLoAlbumin+ hepatoblasts, maintains quiescent and multipotential FL-HSCs. Conversely, the sinusoidal niche, comprising ECs, hepatoblasts and hepatocytes, as well as potential macrophages and megakaryocytes, supports proliferative FL-HSCs biased towards myeloid lineages. Unlike prior reports on the role of Cxcl12, with its depletion from vessel-associated stromal cells leading to 80% of HSCs reduction in the adult bone marrow (BM)6,7, depletion of Cxcl12 via Cdh2CreERT (encoding N-cad) induces altered localization of HSCs from the PV to the sinusoidal niches, resulting in an increase of HSC number but with myeloid-bias. Similarly, we discovered that adult BM encompasses two niches within different zones, each composed of multi-cellular components: trabecular bone area (TBA, or metaphysis) supporting deep-quiescent HSCs, and central marrow (CM, or diaphysis) fostering heterogenous proliferative HSCs. This study transforms our understanding of niches by shifting from single cell-based to multicellular components within distinct zones, illuminating the intricate regulation of HSCs tailored to their different cycling states.

developmental biology↗