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Nature Cell Biology Sep 2020Intestinal stem and progenitor cells replicate and differentiate in distinct compartments, influenced by Wnt, BMP, and other subepithelial cues. The cellular sources of... (Review)
Review
Intestinal stem and progenitor cells replicate and differentiate in distinct compartments, influenced by Wnt, BMP, and other subepithelial cues. The cellular sources of these signals were long obscure because intestinal mesenchyme was insufficiently characterised. In this Review, we discuss how recent mRNA profiles of mouse and human intestinal submucosa, coupled with fine-resolution microscopy and gene and cell disruptions, reveal a coherent picture of an organised tissue carrying cells with distinct molecular properties and functions.
Topics: Animals; Humans; Intestinal Mucosa; Mesoderm; RNA, Messenger; Stem Cell Niche; Wnt Proteins
PubMed: 32884148
DOI: 10.1038/s41556-020-0567-z -
Nature Communications Jan 2023Pancreatic cancer is characterized by abundant desmoplasia, a dense stroma composed of extra-cellular and cellular components, with cancer associated fibroblasts (CAFs)...
Pancreatic cancer is characterized by abundant desmoplasia, a dense stroma composed of extra-cellular and cellular components, with cancer associated fibroblasts (CAFs) being the major cellular component. However, the tissue(s) of origin for CAFs remains controversial. Here we determine the tissue origin of pancreatic CAFs through comprehensive lineage tracing studies in mice. We find that the splanchnic mesenchyme, the fetal cell layer surrounding the endoderm from which the pancreatic epithelium originates, gives rise to the majority of resident fibroblasts in the normal pancreas. In a genetic mouse model of pancreatic cancer, resident fibroblasts expand and constitute the bulk of CAFs. Single cell RNA profiling identifies gene expression signatures that are shared among the fetal splanchnic mesenchyme, adult fibroblasts and CAFs, suggesting a persistent transcriptional program underlies splanchnic lineage differentiation. Together, this study defines the phylogeny of the mesenchymal component of the pancreas and provides insights into pancreatic morphogenesis and tumorigenesis.
Topics: Mice; Animals; Pancreas; Pancreatic Neoplasms; Fibroblasts; Carcinogenesis; Cell Transformation, Neoplastic; Mesoderm; Homeostasis
PubMed: 36596776
DOI: 10.1038/s41467-022-34464-6 -
Current Topics in Developmental Biology 2020Mesoderm and endoderm internalization in the Xenopus embryo are based on a number of region-specific morphogenetic processes that co-act in the vegetal half of the... (Review)
Review
Mesoderm and endoderm internalization in the Xenopus embryo are based on a number of region-specific morphogenetic processes that co-act in the vegetal half of the gastrula. In the multilayered wall surrounding the blastocoel, the apical layer engages in bottle cell formation and associated invagination and involution movements, and in cell intercalation in the plane of the layer. Of these epithelial-type processes, only bottle cell formation has been analyzed mechanistically. In the deep layers of the blastocoel wall, cell-on-cell migration drives the internalization of mesoderm by various forms of involution and of the endodermal cell mass by vegetal rotation. In the mesoderm, cells migrate in a mesenchymal mode with the aid of locomotory protrusions, whereas cells of the vegetal cell mass resemble free bottle cells that engage in ingression-type amoeboid migration. Cells rearrange by differential migration leading to parallel or orthogonal forms of intercalation and respective types of convergent extension. The interaction of the various apical and deep layer processes gives rise to dorsal multilayer invagination, ventrolateral internal involution, peak involution and orthogonal convergent extension of the dorsal posterior mesoderm, vegetal rotation, and blastopore constriction. It is speculated how these multilayer gastrulation movements could be derived from mechanisms in invertebrate single-epithelium gastrulae.
Topics: Animals; Cell Movement; Embryo, Nonmammalian; Endoderm; Gene Expression Regulation, Developmental; Mesoderm; Morphogenesis; Signal Transduction; Xenopus Proteins; Xenopus laevis
PubMed: 31959290
DOI: 10.1016/bs.ctdb.2019.09.002 -
Journal of Visualized Experiments : JoVE Jan 2021Cell dissociation has been an essential procedure for studies at the individual-cell level and/or at a cell-population level (e.g., single cell RNA sequencing and...
Cell dissociation has been an essential procedure for studies at the individual-cell level and/or at a cell-population level (e.g., single cell RNA sequencing and primary cell culture). Yielding viable, healthy cells in large quantities is critical, and the optimal conditions to do so are tissue dependent. Cell populations in the tongue epithelium and underlying mesenchyme/connective tissue are heterogeneous and tissue structures vary in different regions and at different developmental stages. We have tested protocols for isolating cells from the mouse tongue epithelium and mesenchyme/connective tissue in the early developmental [embryonic day 12.5 (E12.5)] and young adult (8-week) stages. A clean separation between the epithelium and underlying mesenchyme/connective tissue was easy to accomplish. However, to further process and isolate cells, yielding viable healthy cells in large quantities, and careful selection of enzymatic digestion buffer, incubation time, and centrifugation speed and time are critical. Incubation of separated epithelium or underlying mesenchyme/connective tissue in 0.25% Trypsin-EDTA for 30 min at 37 °C, followed by centrifugation at 200 x g for 8 min resulted in a high yield of cells at a high viability rate (>90%) regardless of the mouse stages and tongue regions. Moreover, we found that both dissociated epithelial and mesenchymal/connective tissue cells from embryonic and adult tongues could survive in the cell culture-based medium for at least 3 h without a significant decrease of cell viability. The protocols will be useful for studies that require the preparation of isolated cells from mouse tongues at early developmental (E12.5) and young adult (8-week) stages requiring cell dissociation from different tissue compartments.
Topics: Animals; Cell Count; Cell Survival; Connective Tissue; Embryo, Mammalian; Epithelial Cells; Epithelium; Image Processing, Computer-Assisted; Mesoderm; Mice, Inbred C57BL; Tongue; Mice
PubMed: 33554964
DOI: 10.3791/62163 -
Current Topics in Developmental Biology 2024The salivary gland undergoes branching morphogenesis to elaborate into a tree-like structure with numerous saliva-secreting acinar units, all joined by a hierarchical... (Review)
Review
The salivary gland undergoes branching morphogenesis to elaborate into a tree-like structure with numerous saliva-secreting acinar units, all joined by a hierarchical ductal system. The expansive epithelial surface generated by branching morphogenesis serves as the structural basis for the efficient production and delivery of saliva. Here, we elucidate the process of salivary gland morphogenesis, emphasizing the role of mechanics. Structurally, the developing salivary gland is characterized by a stratified epithelium tightly encased by the basement membrane, which is in turn surrounded by a mesenchyme consisting of a dense network of interstitial matrix and mesenchymal cells. Diverse cell types and extracellular matrices bestow this developing organ with organized, yet spatially varied mechanical properties. For instance, the surface epithelial sheet of the bud is highly fluidic due to its high cell motility and weak cell-cell adhesion, rendering it highly pliable. In contrast, the inner core of the bud is more rigid, characterized by reduced cell motility and strong cell-cell adhesion, which likely provide structural support for the tissue. The interactions between the surface epithelial sheet and the inner core give rise to budding morphogenesis. Furthermore, the basement membrane and the mesenchyme offer mechanical constraints that could play a pivotal role in determining the higher-order architecture of a fully mature salivary gland.
Topics: Salivary Glands; Animals; Morphogenesis; Humans; Basement Membrane; Cell Movement; Biomechanical Phenomena; Mesoderm; Cell Adhesion
PubMed: 38937029
DOI: 10.1016/bs.ctdb.2024.05.002 -
Seminars in Cell & Developmental Biology Mar 2023Of all the cell types arising from the neural crest, ectomesenchyme is likely the most unusual. In contrast to the neuroglial cells generated by neural crest throughout... (Review)
Review
Of all the cell types arising from the neural crest, ectomesenchyme is likely the most unusual. In contrast to the neuroglial cells generated by neural crest throughout the embryo, consistent with its ectodermal origin, cranial neural crest-derived cells (CNCCs) generate many connective tissue and skeletal cell types in common with mesoderm. Whether this ectoderm-derived mesenchyme (ectomesenchyme) potential reflects a distinct developmental origin from other CNCC lineages, and/or epigenetic reprogramming of the ectoderm, remains debated. Whereas decades of lineage tracing studies have defined the potential of CNCC ectomesenchyme, these are being revisited by modern genetic techniques. Recent work is also shedding light on the extent to which intrinsic and extrinsic cues determine ectomesenchyme potential, and whether maintenance or reacquisition of CNCC multipotency influences craniofacial repair.
Topics: Neural Crest; Mesoderm; Ectoderm; Embryo, Mammalian
PubMed: 35331627
DOI: 10.1016/j.semcdb.2022.03.018 -
Three-axis classification of mouse lung mesenchymal cells reveals two populations of myofibroblasts.Development (Cambridge, England) Mar 2022The mesenchyme consists of heterogeneous cell populations that support neighboring structures and are integral to intercellular signaling, but are poorly defined...
The mesenchyme consists of heterogeneous cell populations that support neighboring structures and are integral to intercellular signaling, but are poorly defined morphologically and molecularly. Leveraging single-cell RNA-sequencing, 3D imaging and lineage tracing, we classify the mouse lung mesenchyme into three proximal-distal axes that are associated with the endothelium, epithelium and interstitium, respectively. From proximal to distal: the vascular axis includes vascular smooth muscle cells and pericytes that transition as arterioles and venules ramify into capillaries; the epithelial axis includes airway smooth muscle cells and two populations of myofibroblasts - ductal myofibroblasts, surrounding alveolar ducts and marked by CDH4, HHIP and LGR6, which persist post-alveologenesis, and alveolar myofibroblasts, surrounding alveoli and marked by high expression of PDGFRA, which undergo developmental apoptosis; and the interstitial axis, residing between the epithelial and vascular trees and sharing the marker MEOX2, includes fibroblasts in the bronchovascular bundle and the alveolar interstitium, which are marked by IL33/DNER/PI16 and Wnt2, respectively. Single-cell imaging reveals a distinct morphology of mesenchymal cell populations. This classification provides a conceptual and experimental framework applicable to other organs.
Topics: Animals; Lung; Mesenchymal Stem Cells; Mesoderm; Mice; Myofibroblasts; Pulmonary Alveoli
PubMed: 35302583
DOI: 10.1242/dev.200081 -
Developmental Dynamics : An Official... Sep 2021Before limbs or fins, can be patterned and grow they must be initiated. Initiation of the limb first involves designating a portion of lateral plate mesoderm along the... (Review)
Review
Before limbs or fins, can be patterned and grow they must be initiated. Initiation of the limb first involves designating a portion of lateral plate mesoderm along the flank as the site of the future limb. Following specification, a myriad of cellular and molecular events interact to generate a bud that will grow and form the limb. The past three decades has provided a wealth of understanding on how those events generate the limb bud and how variations in them result in different limb forms. Comparatively, much less attention has been given to the earliest steps of limb formation and what impacts altering the position and initiation of the limb have had on evolution. Here, we first review the processes and pathways involved in these two phases of limb initiation, as determined from amniote model systems. We then broaden our scope to examine how variation in the limb initiation module has contributed to biological diversity in amniotes. Finally, we review what is known about limb initiation in fish and amphibians, and consider what mechanisms are conserved across vertebrates.
Topics: Animals; Biological Evolution; Extremities; Gene Expression Regulation, Developmental; Limb Buds; Mesoderm; Vertebrates
PubMed: 33522040
DOI: 10.1002/dvdy.308 -
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 -
Cellular and Molecular Life Sciences :... May 2020Vertebrate cranial mesoderm is a discrete developmental unit compared to the mesoderm below the developing neck. An extraordinary feature of the cranial mesoderm is that... (Review)
Review
Vertebrate cranial mesoderm is a discrete developmental unit compared to the mesoderm below the developing neck. An extraordinary feature of the cranial mesoderm is that it includes a common progenitor pool contributing to the chambered heart and the craniofacial skeletal muscles. This striking developmental potential and the excitement it generated led to advances in our understanding of cranial mesoderm developmental mechanism. Remarkably, recent findings have begun to unravel the origin of its distinct developmental characteristics. Here, we take a detailed view of the ontogenetic trajectory of cranial mesoderm and its regulatory network. Based on the emerging evidence, we propose that cranial and posterior mesoderm diverge at the earliest step of the process that patterns the mesoderm germ layer along the anterior-posterior body axis. Further, we discuss the latest evidence and their impact on our current understanding of the evolutionary origin of cranial mesoderm. Overall, the review highlights the findings from contemporary research, which lays the foundation to probe the molecular basis of unique developmental potential and evolutionary origin of cranial mesoderm.
Topics: Animals; Biological Evolution; Gene Expression Regulation, Developmental; Humans; Mesoderm; Muscle Development; Muscle, Skeletal; Neural Crest; Skull; Vertebrates
PubMed: 31722070
DOI: 10.1007/s00018-019-03373-1