Browsing by Subject "Mouse embryo"

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    Ectopic Noggin in a Population of Nfatc1 Lineage Endocardial Progenitors Induces Embryonic Lethality
    (MDPI AG (Basel, Switzerland), 2014-11-20) Snider, Paige; Simmons, Olga; Wang, Jian; Hoang, Chinh Q.; Conway, Simon J.; Department of Pediatrics, IU School of Medicine
    The initial heart is composed of a myocardial tube lined by endocardial cells. The TGFβ superfamily is known to play an important role, as BMPs from the myocardium signal to the overlying endocardium to create an environment for EMT. Subsequently, BMP and TGFβ signaling pathways synergize to form primitive valves and regulate myocardial growth. In this study, we investigated the requirement of BMP activity by transgenic over-expression of extracellular BMP antagonist Noggin. Using Nfatc1Cre to drive lineage-restricted Noggin within the endocardium, we show that ectopic Noggin arrests cardiac development in E10.5-11 embryos, resulting in small hearts which beat poorly and die by E12.5. This is coupled with hypoplastic endocardial cushions, reduced trabeculation and fewer mature contractile fibrils in mutant hearts. Moreover, Nfatc1Cre -mediated diphtheria toxin fragment-A expression in the endocardium resulted in genetic ablation and a more severe phenotype with lethality at E11 and abnormal linear hearts. Molecular analysis demonstrated that endocardial Noggin resulted in a specific alteration of TGFβ/BMP-mediated signal transduction, in that, both Endoglin and ALK1 were downregulated in mutant endocardium. Combined, these results demonstrate the cell-autonomous requirement of the endocardial lineage and function of unaltered BMP levels in facilitating endothelium-cardiomyocyte cross-talk and promoting endocardial cushion formation.
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    Long-Term Engraftment of ESC-Derived B-1 Progenitor Cells Supports HSC-Independent Lymphopoiesis
    (Elsevier, 2019-03-05) Lin, Yang; Kobayashi, Michihiro; Portilho, Nathalia Azevedo; Mishra, Akansha; Gao, Hongyu; Liu, Yunlong; Wenzel, Pamela; Davis, Brian; Yoder, Mervin C.; Yoshimoto, Momoko; Pediatrics, School of Medicine
    It is generally considered that mouse embryonic stem cell (ESC) differentiation into blood cells in vitro recapitulates yolk sac (YS) hematopoiesis. As such, similar to YS-derived B-progenitors, we demonstrate here that ESC-derived B-progenitors differentiate into B-1 and marginal zone B cells, but not B-2 cells in immunodeficient mice after transplantation. ESC-derived B-1 cells were maintained in the recipients for more than 6 months, secreting natural IgM antibodies in vivo. Gene expression profiling displayed a close relationship between ESC- and YS-derived B-1 progenitors. Because there are no hematopoietic stem cells (HSCs) detectable in our ESC differentiation culture, successful long-term engraftment of ESC-derived functional B-1 cells supports the presence of HSC-independent B-1 cell development.