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To delineate the ontogeny of the mammalian endoderm, we generated 112,217 single-cell transcriptomes representing all endoderm populations within the mouse embryo until midgestation. By using graph-based approaches, we modelled differentiating cells for spatio-temporal characterization of developmental trajectories and defined the transcriptional architecture that accompanies the emergence of the first (primitive or extra-embryonic) endodermal population and its sister pluripotent (embryonic) epiblast lineage. We uncovered a relationship between descendants of these two lineages, whereby epiblast cells differentiate into endoderm at two distinct time points, before and during gastrulation. Trajectories of endoderm cells were mapped as they acquired embryonic versus extra-embryonic fates, and as they spatially converged within the nascent gut endoderm; revealing them to be globally similar but retaining aspects of their lineage history. We observed the regionalized identity of cells along the anterior-posterior axis of the emergent gut tube, reflecting their embryonic or extra-embryonic origin, and their coordinate patterning into organ-specific territories.
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The three germ layers - mesoderm, endoderm and ectoderm - constituting the cellular blueprint for the tissues and organs that will form during embryonic development, are specified at gastrulation. Cel...
Following implantation, the epiblast (EPI) cells transit from the naive to primed pluripotency, accompanied by dynamic changes in X chromosome activity in females. To investigate the molecular attribu...
Studies in vertebrates have outlined conserved molecular control of definitive endoderm (END) development. However, recent work also shows that key molecular aspects of human END regulation differ eve...
The Erk mitogen-activated protein kinase plays diverse roles in animal development. Its widespread reuse raises a conundrum: when a single kinase like Erk is activated, how does a developing cell know...
Cell-cell communication via ligand-receptor signaling is a fundamental feature of complex organs. Despite this, the global landscape of intercellular signaling in mammalian liver has not been elucidat...
The investigators propose to conduct a pilot feasibility study of single agent afatinib in patients with previously untreated metastatic EGFR (epidermal growth factor receptor) mutant aden...
The investigators propose to conduct a retrospective study of single agent ceritinib in patients with previously untreated anaplastic lymphoma kinase (ALK) rearranged adenocarcinoma of the...
The aim of this study is to establish large tissue sections for 10 kinds of tumors. in order to observe the tumor landscape on microscope. The tumors including esophageal carcinoma,gastric...
Though cervical insufficiency is a common cause of second trimester pregnancy loss, the placement of an emergent cerclage in these patients is thought to improve perinatal outcomes. It is ...
Using sickle cell and thalassemia mouse models, researchers will evaluate the possibility of correcting these disorders by inserting healthy genetic material into the diseased blood cells....
A homeodomain protein and transcription regulator that functions in BLASTOCYST INNER CELL MASS and EMBRYONIC STEM CELL proliferation and CELL SELF RENEWAL. It confers pluripotency on embryonic stem cells and prevents their differentiation towards extraembryonic ENDODERM and trophectoderm (TROPHOBLAST) CELL LINEAGES.
PLURIPOTENT STEM CELLS derived from the BLASTOCYST INNER CELL MASS of day 3.5 mouse embryos.
High resolution imaging techniques that allow visualization of individual molecules of proteins, lipids, or nucleic acids within cells or tissues.
An imaging technique using compounds labelled with short-lived positron-emitting radionuclides (such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18) to measure cell metabolism. It has been useful in study of soft tissues such as CANCER; CARDIOVASCULAR SYSTEM; and brain. SINGLE-PHOTON EMISSION-COMPUTED TOMOGRAPHY is closely related to positron emission tomography, but uses isotopes with longer half-lives and resolution is lower.
Mouse strains constructed to possess identical genotypes except for a difference at a single gene locus.
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