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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 -
Cells Nov 2020Pancreatic ductal adenocarcinoma (PDA) is characterized by an extensive fibroinflammatory microenvironment that accumulates from the onset of disease progression.... (Review)
Review
Pancreatic ductal adenocarcinoma (PDA) is characterized by an extensive fibroinflammatory microenvironment that accumulates from the onset of disease progression. Cancer-associated fibroblasts (CAFs) are a prominent cellular component of the stroma, but their role during carcinogenesis remains controversial, with both tumor-supporting and tumor-restraining functions reported in different studies. One explanation for these contradictory findings is the heterogeneous nature of the fibroblast populations, and the different roles each subset might play in carcinogenesis. Here, we review the current literature on the origin and function of pancreatic fibroblasts, from the developing organ to the healthy adult pancreas, and throughout the initiation and progression of PDA. We also discuss clinical approaches to targeting fibroblasts in PDA.
Topics: Animals; Cancer-Associated Fibroblasts; Embryonic Development; Fibroblasts; Humans; Mesoderm; Pancreas; Pancreatic Neoplasms
PubMed: 33198201
DOI: 10.3390/cells9112464 -
FEBS Letters Dec 2019The haematopoietic system is established during embryonic life through a series of developmental steps that culminates with the generation of haematopoietic stem cells.... (Review)
Review
The haematopoietic system is established during embryonic life through a series of developmental steps that culminates with the generation of haematopoietic stem cells. Characterisation of the transcriptional network that regulates blood cell emergence has led to the identification of transcription factors essential for this process. Among the many factors wired within this complex regulatory network, ETV2, SCL and RUNX1 are the central components. All three factors are absolutely required for blood cell generation, each one controlling a precise step of specification from the mesoderm germ layer to fully functional blood progenitors. Insight into the transcriptional control of blood cell emergence has been used for devising protocols to generate blood cells de novo, either through reprogramming of somatic cells or through forward programming of pluripotent stem cells. Interestingly, the physiological process of blood cell generation and its laboratory-engineered counterpart have very little in common.
Topics: Blood Cells; Cell Differentiation; Cellular Reprogramming; Core Binding Factor Alpha 2 Subunit; Hematopoietic Stem Cells; Humans; Mesoderm; Pluripotent Stem Cells; T-Cell Acute Lymphocytic Leukemia Protein 1; Transcription Factors; Transcriptional Activation
PubMed: 31432499
DOI: 10.1002/1873-3468.13585 -
ELife Jan 2022During the development of the vertebrate embryo, segmented structures called somites are periodically formed from the presomitic mesoderm (PSM) and give rise to the...
During the development of the vertebrate embryo, segmented structures called somites are periodically formed from the presomitic mesoderm (PSM) and give rise to the vertebral column. While somite formation has been studied in several animal models, it is less clear how well this process is conserved in humans. Recent progress has made it possible to study aspects of human paraxial mesoderm (PM) development such as the human segmentation clock using human pluripotent stem cells (hPSCs); however, somite formation has not been observed in these monolayer cultures. Here, we describe the generation of human PM organoids from hPSCs (termed Somitoids), which recapitulate the molecular, morphological, and functional features of PM development, including formation of somite-like structures . Using a quantitative image-based screen, we identify critical parameters such as initial cell number and signaling modulations that reproducibly yielded formation of somite-like structures in our organoid system. In addition, using single-cell RNA-sequencing and 3D imaging, we show that PM organoids both transcriptionally and morphologically resemble their counterparts and can be differentiated into somite derivatives. Our organoid system is reproducible and scalable, allowing for the systematic and quantitative analysis of human spine development and disease .
Topics: Animals; Cell Differentiation; Humans; Mesoderm; Organoids; Pluripotent Stem Cells; Somites
PubMed: 35088712
DOI: 10.7554/eLife.68925 -
Developmental Cell Mar 2022Human pluripotent stem cells (hPSCs) can self-renew indefinitely or can be induced to differentiate. We previously showed that exogenous glutamine (Gln) withdrawal...
Human pluripotent stem cells (hPSCs) can self-renew indefinitely or can be induced to differentiate. We previously showed that exogenous glutamine (Gln) withdrawal biased hPSC differentiation toward ectoderm and away from mesoderm. We revealed that, although all three germ lineages are capable of de novo Gln synthesis, only ectoderm generates sufficient Gln to sustain cell viability and differentiation, and this finding clarifies lineage fate restrictions under Gln withdrawal. Furthermore, we found that Gln acts as a signaling molecule for ectoderm that supersedes lineage-specifying cytokine induction. In contrast, Gln in mesoderm and endoderm is the preferred precursor of α-ketoglutarate without a direct signaling role. Our work raises a question about whether the nutrient environment functions directly in cell differentiation during development. Interestingly, transcriptome analysis of a gastrulation-stage human embryo shows that unique Gln enzyme-encoding gene expression patterns may also distinguish germ lineages in vivo. Together, our study suggests that intracellular Gln may help coordinate differentiation of the three germ layers.
Topics: Cell Differentiation; Cell Lineage; Endoderm; Germ Layers; Glutamine; Humans; Mesoderm; Pluripotent Stem Cells
PubMed: 35216682
DOI: 10.1016/j.devcel.2022.02.003 -
Mechanisms of Development Sep 2020Gastrulation is generally understood as the morphogenetic processes that result in the spatial organization of the blastomere into the three germ layers, ectoderm,... (Review)
Review
Gastrulation is generally understood as the morphogenetic processes that result in the spatial organization of the blastomere into the three germ layers, ectoderm, mesoderm and endoderm. This review summarizes our current knowledge of the morphogenetic mechanisms in Drosophila gastrulation. In addition to the events that drive mesoderm invagination and germband elongation, we pay particular attention to other, less well-known mechanisms including midgut invagination, cephalic furrow formation, dorsal fold formation, and mesoderm layer formation. This review covers topics ranging from the identification and functional characterization of developmental and morphogenetic control genes to the analysis of the physical properties of cells and tissues and the control of cell and tissue mechanics of the morphogenetic movements in the gastrula.
Topics: Animals; Biomechanical Phenomena; Drosophila melanogaster; Ectoderm; Embryo, Nonmammalian; Endoderm; Gastrula; Gastrulation; Gene Expression Regulation, Developmental; Mesoderm; Morphogenesis
PubMed: 32615151
DOI: 10.1016/j.mod.2020.103629 -
Cold Spring Harbor Protocols Nov 2022Marginal zone explants from embryos can be used to expose cell behaviors and tissue movements that normally operate in dorsal tissues. Dorsal explants comprise the...
Marginal zone explants from embryos can be used to expose cell behaviors and tissue movements that normally operate in dorsal tissues. Dorsal explants comprise the diverse set of progenitor cells found in dorsal tissues including mesendoderm, head mesoderm, prechordal mesoderm, endoderm with bottle cells, axial mesoderm of the prospective notochord, paraxial mesoderm of the somites, lateral plate mesoderm, neural ectoderm, and ectoderm. Unlike an organoid, the dorsal marginal zone (DMZ) explant is "organotypic" in that microsurgery does not disrupt native tissue organization beyond manipulations needed to dissect the tissue from the embryo. An organotypic early gastrula DMZ explant preserves boundaries and close tissue associations in the native marginal zone. Depending on the stage, patterning and cell identities can be maintained in explants and tissue isolates. Local cell movements and behaviors may also be preserved; however, the large-scale biomechanical impact of their collective movements may be altered from those in the native marginal zone. For instance, involution is typically inhibited in the DMZ explant, precluding the two-layer association of mesoderm and prospective neural ectoderm normally achieved during gastrulation. DMZ explants may be mounted and imaged in a variety of ways, exposing interesting cell behaviors or collective movements such as mediolateral cell intercalation in the axial and paraxial mesoderm, apical constriction of bottle cells, and directional migration of mesendoderm. The flattened DMZ explant can also be used to study emergence of new tissue-defining boundaries such as the notochord-somite boundary, the ectoderm-mesoderm boundary, and the mesendoderm-mesoderm boundary.
Topics: Animals; Gastrula; Prospective Studies; Mesoderm; Xenopus laevis; Ectoderm
PubMed: 35577522
DOI: 10.1101/pdb.prot097360 -
Cells & Development Dec 2021In vertebrate embryos the presomitic mesoderm becomes progressively segmented into somites at the anterior end while extending along the anterior-posterior axis. A...
In vertebrate embryos the presomitic mesoderm becomes progressively segmented into somites at the anterior end while extending along the anterior-posterior axis. A commonly adopted model to explain how this tissue elongates is that of posterior growth, driven in part by the addition of new cells from uncommitted progenitor populations in the tailbud. However, in zebrafish, much of somitogenesis is associated with an absence of overall volume increase, and posterior progenitors do not contribute new cells until the final stages of somitogenesis. Here, we perform a comprehensive 3D morphometric analysis of the paraxial mesoderm and reveal that extension is linked to a volumetric decrease and an increase in cell density. We also find that individual cells decrease in volume over successive somite stages. Live cell tracking confirms that much of this tissue deformation occurs within the presomitic mesoderm progenitor zone and is associated with non-directional rearrangement. Taken together, we propose a compaction-extension mechanism of tissue elongation that highlights the need to better understand the role tissue intrinsic and extrinsic forces in regulating morphogenesis.
Topics: Animals; Embryonic Development; Mesoderm; Morphogenesis; Somites; Zebrafish
PubMed: 34597846
DOI: 10.1016/j.cdev.2021.203748 -
Cell Reports Aug 2022Embryonic stem cells (ESCs) can adopt lineage-specific gene-expression programs by stepwise exposure to defined factors, resulting in the generation of functional cell...
Embryonic stem cells (ESCs) can adopt lineage-specific gene-expression programs by stepwise exposure to defined factors, resulting in the generation of functional cell types. Bulk and single-cell-based assays were employed to catalog gene expression, histone modifications, chromatin conformation, and accessibility transitions in ESC populations and individual cells acquiring a presomitic mesoderm fate and undergoing further specification toward myogenic and neurogenic lineages. These assays identified cis-regulatory regions and transcription factors presiding over gene-expression programs occurring at defined ESC transitions and revealed the presence of heterogeneous cell populations within discrete ESC developmental stages. The datasets were employed to identify previously unappreciated genomic elements directing the initial activation of Pax7 and myogenic and neurogenic gene-expression programs. This study provides a resource for the discovery of genomic and transcriptional features of pluripotent, mesoderm-induced ESCs and ESC-derived cell lineages.
Topics: Cell Differentiation; Embryonic Stem Cells; Gene Expression Regulation, Developmental; Mesoderm; Regulatory Sequences, Nucleic Acid; Transcriptome
PubMed: 35977485
DOI: 10.1016/j.celrep.2022.111219 -
The EMBO Journal Apr 2022Mesoderm arises at gastrulation and contributes to both the mouse embryo proper and its extra-embryonic membranes. Two-photon live imaging of embryos bearing a keratin...
Mesoderm arises at gastrulation and contributes to both the mouse embryo proper and its extra-embryonic membranes. Two-photon live imaging of embryos bearing a keratin reporter allowed recording filament nucleation and elongation in the extra-embryonic region. Upon separation of amniotic and exocoelomic cavities, keratin 8 formed apical cables co-aligned across multiple cells in the amnion, allantois, and blood islands. An influence of substrate rigidity and composition on cell behavior and keratin content was observed in mesoderm explants. Embryos lacking all keratin filaments displayed a deflated extra-embryonic cavity, a narrow thick amnion, and a short allantois. Single-cell RNA sequencing of sorted mesoderm cells and micro-dissected amnion, chorion, and allantois, provided an atlas of transcriptomes with germ layer and regional information. It defined the cytoskeleton and adhesion expression profile of mesoderm-derived keratin 8-enriched cells lining the exocoelomic cavity. Those findings indicate a novel role for keratin filaments in the expansion of extra-embryonic structures and suggest mechanisms of mesoderm adaptation to the environment.
Topics: Animals; Embryo, Mammalian; Extraembryonic Membranes; Gastrulation; Keratins; Mesoderm; Mice
PubMed: 35266581
DOI: 10.15252/embj.2021108747