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Integrated Local and Systemic Communication Factors Regulate Nascent Hematopoietic Progenitor Escape During Developmental Hematopoiesis.
Int J Mol Sci
December 2024
Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Mammalian blood cells originate from specialized 'hemogenic' endothelial (HE) cells in major arteries. During the endothelial-to-hematopoietic transition (EHT), nascent hematopoietic stem cells (HSCs) bud from the arterial endothelial wall and enter circulation, destined to colonize the fetal liver before ultimately migrating to the bone marrow. Mechanisms and processes that facilitate EHT and the release of nascent HSCs are incompletely understood, but may involve signaling from neighboring vascular endothelial cells, stromal support cells, circulating pre-formed hematopoietic cells, and/or systemic factors secreted by distal organs.
View Article and Find Full Text PDFIP6K1 rewires LKB1 signaling to mediate hyperglycemic endothelial senescence.
Diabetes
January 2025
Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Diabetes is a major risk factor for cardiovascular disease, but the molecular mechanisms underlying diabetic vasculopathy have been elusive. Here we report that inositol hexakisphosphate kinase 1 (IP6K1) mediates hyperglycemia-induced endothelial senescence by rewiring the liver kinase B1 (LKB1) signaling from activating the adenosine monophosphate-activated protein kinase (AMPK) pathway to the p53 pathway. We found that hyperglycemia upregulated IP6K1, which disrupts the Hsp/Hsc70 and carboxyl terminus of Hsc70-interacting protein (CHIP)-mediated LKB1 degradation, leading to increased expression levels of LKB1.
View Article and Find Full Text PDFPancreatic organogenesis mapped through space and time.
Exp Mol Med
January 2025
Program in Developmental Biology, Baylor College of Medicine, Houston, TX, USA.
The spatial organization of cells within a tissue is dictated throughout dynamic developmental processes. We sought to understand whether cells geometrically coordinate with one another throughout development to achieve their organization. The pancreas is a complex cellular organ with a particular spatial organization.
View Article and Find Full Text PDFTopology-based segmentation of 3D confocal images of emerging hematopoietic stem cells in the zebrafish embryo.
Biol Imaging
November 2024
Biological Image Analysis Unit, Institut Pasteur, Université Paris Cité, Paris, France.
We develop a novel method for image segmentation of 3D confocal microscopy images of emerging hematopoietic stem cells. The method is based on the theory of persistent homology and uses an optimal threshold to select the most persistent cycles in the persistence diagram. This enables the segmentation of the image's most contrasted and representative shapes.
View Article and Find Full Text PDFSpatiotemporal dynamics of fetal liver hematopoietic niches.
J Exp Med
February 2025
Immunology Department, Unit of Lymphocytes and Immunity, Institut Pasteur, Paris, France.
Embryonic hematopoietic cells develop in the fetal liver (FL), surrounded by diverse non-hematopoietic stromal cells. However, the spatial organization and cytokine production patterns of the stroma during FL development remain poorly understood. Here, we characterized and mapped the hematopoietic and stromal cell populations at early (E12.
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