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Cell Jul 2016Stem-cell differentiation to desired lineages requires navigating alternating developmental paths that often lead to unwanted cell types. Hence, comprehensive...
Stem-cell differentiation to desired lineages requires navigating alternating developmental paths that often lead to unwanted cell types. Hence, comprehensive developmental roadmaps are crucial to channel stem-cell differentiation toward desired fates. To this end, here, we map bifurcating lineage choices leading from pluripotency to 12 human mesodermal lineages, including bone, muscle, and heart. We defined the extrinsic signals controlling each binary lineage decision, enabling us to logically block differentiation toward unwanted fates and rapidly steer pluripotent stem cells toward 80%-99% pure human mesodermal lineages at most branchpoints. This strategy enabled the generation of human bone and heart progenitors that could engraft in respective in vivo models. Mapping stepwise chromatin and single-cell gene expression changes in mesoderm development uncovered somite segmentation, a previously unobservable human embryonic event transiently marked by HOPX expression. Collectively, this roadmap enables navigation of mesodermal development to produce transplantable human tissue progenitors and uncover developmental processes. VIDEO ABSTRACT.
Topics: Bone Morphogenetic Proteins; Bone and Bones; Heart; Homeodomain Proteins; Humans; Mesoderm; Myocytes, Cardiac; Pluripotent Stem Cells; Primitive Streak; Signal Transduction; Single-Cell Analysis; Somites; Stem Cells; Tumor Suppressor Proteins; Wnt Proteins
PubMed: 27419872
DOI: 10.1016/j.cell.2016.06.011 -
The International Journal of... 2018Striated muscle is the most abundant tissue in the body of vertebrates and it forms, together with the skeleton, the locomotory system required both for movement and the... (Review)
Review
Striated muscle is the most abundant tissue in the body of vertebrates and it forms, together with the skeleton, the locomotory system required both for movement and the creation of the specific body shape of a species. Research on the embryonic development of muscles has a long tradition both in classical embryology and in molecular developmental biology. While the gene networks regulating muscle development have been discovered mostly in the mouse through genetics, our knowledge on cell lineages, muscle morphogenesis and tissue interactions regulating their formation is to a large extent based on the use of the avian model. This review highlights present knowledge of the development of skeletal muscle in vertebrate embryos. Special focus will be placed on the contributions from chicken and quail embryo model systems.
Topics: Animals; Cell Differentiation; Cell Lineage; Chick Embryo; Chickens; Electroporation; Embryonic Development; Mesoderm; Mice; Morphogenesis; Muscle Development; Quail; Signal Transduction; Somites; Stem Cells
PubMed: 29616720
DOI: 10.1387/ijdb.170312cm -
ELife Jun 2022Advanced imaging techniques reveal details of the interactions between the two layers of the embryonic midgut that influence its ultimate shape.
Advanced imaging techniques reveal details of the interactions between the two layers of the embryonic midgut that influence its ultimate shape.
Topics: Animals; Drosophila; Endoderm; Gene Expression Regulation, Developmental; Mesoderm; Morphogenesis
PubMed: 35771125
DOI: 10.7554/eLife.80416 -
Seminars in Cell & Developmental Biology Jul 2022The discovery of mesoderm inducing signals helped usher in the era of molecular developmental biology, and today the mechanisms of mesoderm induction and patterning are... (Review)
Review
The discovery of mesoderm inducing signals helped usher in the era of molecular developmental biology, and today the mechanisms of mesoderm induction and patterning are still intensely studied. Mesoderm induction begins during gastrulation, but recent evidence in vertebrates shows that this process continues after gastrulation in a group of posteriorly localized cells called neuromesodermal progenitors (NMPs). NMPs reside within the post-gastrulation embryonic structure called the tailbud, where they make a lineage decision between ectoderm (spinal cord) and mesoderm. The majority of NMP-derived mesoderm generates somites, but also contributes to lateral mesoderm fates such as endothelium. The discovery of NMPs provides a new paradigm in which to study vertebrate mesoderm induction. This review will discuss mechanisms of mesoderm induction within NMPs, and how they have informed our understanding of mesoderm induction more broadly within vertebrates as well as animal species outside of the vertebrate lineage. Special focus will be given to the signaling networks underlying NMP-derived mesoderm induction and patterning, as well as emerging work on the significance of partial epithelial-mesenchymal states in coordinating cell fate and morphogenesis.
Topics: Animals; Body Patterning; Cell Differentiation; Gastrulation; Gene Expression Regulation, Developmental; Mesoderm; Somites
PubMed: 34840081
DOI: 10.1016/j.semcdb.2021.11.010 -
The Journal of Biological Chemistry Jun 2017Critical steps in the specification of embryonic cell lineages occur after implantation, but gaining insight into the molecular details of these cellular processes has... (Review)
Review
Critical steps in the specification of embryonic cell lineages occur after implantation, but gaining insight into the molecular details of these cellular processes has been challenging. Jin and co-workers now report the transcriptomic signatures and molecular heterogeneity of more than 600 single cells from mouse embryos at days 5.5 and 6.5, advancing our understanding of how early embryonic cells make cell-fate decisions into mesoderm and endoderm lineages.
Topics: Animals; Cell Lineage; Embryo, Mammalian; Endoderm; Mesoderm; Mice
PubMed: 28600307
DOI: 10.1074/jbc.H117.780585 -
Nature Communications Jun 2021Positional information driving limb muscle patterning is contained in connective tissue fibroblasts but not in myogenic cells. Limb muscles originate from somites, while...
Positional information driving limb muscle patterning is contained in connective tissue fibroblasts but not in myogenic cells. Limb muscles originate from somites, while connective tissues originate from lateral plate mesoderm. With cell and genetic lineage tracing we challenge this model and identify an unexpected contribution of lateral plate-derived fibroblasts to the myogenic lineage, preferentially at the myotendinous junction. Analysis of single-cell RNA-sequencing data from whole limbs at successive developmental stages identifies a population displaying a dual muscle and connective tissue signature. BMP signalling is active in this dual population and at the tendon/muscle interface. In vivo and in vitro gain- and loss-of-function experiments show that BMP signalling regulates a fibroblast-to-myoblast conversion. These results suggest a scenario in which BMP signalling converts a subset of lateral plate mesoderm-derived cells to a myogenic fate in order to create a boundary of fibroblast-derived myonuclei at the myotendinous junction that controls limb muscle patterning.
Topics: Animals; Body Patterning; Cell Lineage; Cells, Cultured; Chick Embryo; Extremities; Fibroblasts; Gene Expression Regulation, Developmental; Mesoderm; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Transgenic; Muscle Development; Muscle, Skeletal; Reverse Transcriptase Polymerase Chain Reaction; Somites; Mice
PubMed: 34158501
DOI: 10.1038/s41467-021-24157-x -
Current Opinion in Cell Biology Dec 2019The three germ layers - mesoderm, endoderm and ectoderm - constituting the cellular blueprint for the tissues and organs that will form during embryonic development, are... (Review)
Review
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. Cells of mesodermal origin are the most abundant in the human body, representing a great variety of cell types, including the musculoskeletal system (bone, cartilage and muscle), cardiovascular system (heart, blood and blood vessels), as well as the connective tissues found throughout our bodies. A long-standing question pertains how this panoply of mesodermal cell types arises in a stereotypical fashion in time and space. This review discusses the events associated with mesoderm specification, highlighting the reconstruction of putative developmental trajectories facilitated by recent single-cell 'omic' data. We will also discuss the potential of emergent organoid systems to emulate and interrogate the dynamics of lineage specification at cellular resolution.
Topics: Animals; Cell Differentiation; Cell Lineage; Ectoderm; Embryonic Development; Endoderm; Gastrulation; Humans; Mesoderm
PubMed: 31476530
DOI: 10.1016/j.ceb.2019.07.012 -
International Journal of Molecular... Aug 2021To ensure the formation of a properly patterned embryo, multiple processes must operate harmoniously at sequential phases of development. This is implemented by mutual... (Review)
Review
To ensure the formation of a properly patterned embryo, multiple processes must operate harmoniously at sequential phases of development. This is implemented by mutual interactions between cells and tissues that together regulate the segregation and specification of cells, their growth and morphogenesis. The formation of the spinal cord and paraxial mesoderm derivatives exquisitely illustrate these processes. Following early gastrulation, while the vertebrate body elongates, a population of bipotent neuromesodermal progenitors resident in the posterior region of the embryo generate both neural and mesodermal lineages. At later stages, the somitic mesoderm regulates aspects of neural patterning and differentiation of both central and peripheral neural progenitors. Reciprocally, neural precursors influence the paraxial mesoderm to regulate somite-derived myogenesis and additional processes by distinct mechanisms. Central to this crosstalk is the activity of the axial notochord, which, via sonic hedgehog signaling, plays pivotal roles in neural, skeletal muscle and cartilage ontogeny. Here, we discuss the cellular and molecular basis underlying this complex developmental plan, with a focus on the logic of sonic hedgehog activities in the coordination of the neural-mesodermal axis.
Topics: Animals; Cell Differentiation; Embryonic Stem Cells; Gene Expression Regulation, Developmental; Hedgehog Proteins; Humans; Mesoderm; Neural Tube
PubMed: 34502050
DOI: 10.3390/ijms22179141 -
Archives of Pathology & Laboratory... Sep 2014Placental mesenchymal dysplasia is a rare placental lesion characterized by stem villous cystic dilation and vesicle formation, placentomegaly, and vascular... (Review)
Review
Placental mesenchymal dysplasia is a rare placental lesion characterized by stem villous cystic dilation and vesicle formation, placentomegaly, and vascular abnormalities. It can be associated with growth restriction, stillbirth, Beckwith-Wiedemann syndrome, and some chromosomal abnormalities, and needs to be distinguished from its main differential diagnosis, hydatidiform mole.
Topics: Beckwith-Wiedemann Syndrome; Chromosome Aberrations; Diagnosis, Differential; Female; Fetal Growth Retardation; Humans; Hydatidiform Mole; Mesoderm; Placenta; Placenta Diseases; Pregnancy
PubMed: 25171710
DOI: 10.5858/arpa.2013-0399-RS -
Genetics Jun 2020Mesoderm migration in the embryo is a highly conserved, complex process that is required for the formation of specialized tissues and organs, including the somatic and... (Review)
Review
Mesoderm migration in the embryo is a highly conserved, complex process that is required for the formation of specialized tissues and organs, including the somatic and visceral musculature. In this FlyBook chapter, we will compare and contrast the specification and migration of cells originating from the trunk and caudal mesoderm. Both cell types engage in collective migrations that enable cells to achieve new positions within developing embryos and form distinct tissues. To start, we will discuss specification and early morphogenetic movements of the presumptive mesoderm, then focus on the coordinate movements of the two subtypes trunk mesoderm and caudal visceral mesoderm, ending with a comparison of these processes including general insights gained through study.
Topics: Animals; Cell Movement; Drosophila; Drosophila Proteins; Embryo, Nonmammalian; Gene Expression Regulation, Developmental; Mesoderm; Myoblasts
PubMed: 32487692
DOI: 10.1534/genetics.120.303258