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Cellular and Molecular Life Sciences :... Oct 2018Mesenchymoangioblast (MB) is the earliest precursor for endothelial and mesenchymal cells originating from APLNRPDGFRαKDR mesoderm in human pluripotent stem cell... (Review)
Review
Mesenchymoangioblast (MB) is the earliest precursor for endothelial and mesenchymal cells originating from APLNRPDGFRαKDR mesoderm in human pluripotent stem cell cultures. MBs are identified based on their capacity to form FGF2-dependent compact spheroid colonies in a serum-free semisolid medium. MBs colonies are composed of PDGFRβCD271EMCNDLK1CD73 primitive mesenchymal cells which are generated through endothelial/angioblastic intermediates (cores) formed during first 3-4 days of clonogenic cultures. MB-derived primitive mesenchymal cells have potential to differentiate into mesenchymal stromal/stem cells (MSCs), pericytes, and smooth muscle cells. In this review, we summarize the specification and developmental potential of MBs, emphasize features that distinguish MBs from other mesenchymal progenitors described in the literature and discuss the value of these findings for identifying molecular pathways leading to MSC and vasculogenic cell specification, and developing cellular therapies using MB-derived progeny.
Topics: Autoimmune Diseases; Cell Lineage; Embryonic Development; Endothelial Cells; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mesoderm; Pluripotent Stem Cells; Spheroids, Cellular
PubMed: 29992471
DOI: 10.1007/s00018-018-2871-3 -
International Journal of Molecular... Apr 2019Congenital anomalies of the kidney and urinary tract (CAKUT) are common birth defects derived from abnormalities in renal differentiation during embryogenesis. CAKUT is... (Review)
Review
Congenital anomalies of the kidney and urinary tract (CAKUT) are common birth defects derived from abnormalities in renal differentiation during embryogenesis. CAKUT is the major cause of end-stage renal disease and chronic kidney diseases in children, but its genetic causes remain largely unresolved. Here we discuss advances in the understanding of how mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) activity contributes to the regulation of ureteric bud branching morphogenesis, which dictates the final size, shape, and nephron number of the kidney. Recent studies also demonstrate that the MAPK/ERK pathway is directly involved in nephrogenesis, regulating both the maintenance and differentiation of the nephrogenic mesenchyme. Interestingly, aberrant MAPK/ERK signaling is linked to many cancers, and recent studies suggest it also plays a role in the most common pediatric renal cancer, Wilms' tumor.
Topics: Animals; Cell Differentiation; Humans; Kidney; MAP Kinase Signaling System; Mesoderm; Organogenesis
PubMed: 30974877
DOI: 10.3390/ijms20071779 -
ELife Mar 2016Experiments in mice shed new light on an elusive population of embryonic cells called neuromesodermal progenitors.
Experiments in mice shed new light on an elusive population of embryonic cells called neuromesodermal progenitors.
Topics: Animals; Gene Expression Regulation, Developmental; Mesoderm; Mice
PubMed: 26949247
DOI: 10.7554/eLife.14830 -
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 -
Developmental Biology May 2020Vertebrate head morphogenesis involves carefully-orchestrated tissue growth and cell movements of the mesoderm and neural crest to form the distinct craniofacial...
Vertebrate head morphogenesis involves carefully-orchestrated tissue growth and cell movements of the mesoderm and neural crest to form the distinct craniofacial pattern. To better understand structural birth defects, it is important that we characterize the dynamics of these processes and learn how they rely on each other. Here we examine this question during chick head morphogenesis using time-lapse imaging, computational modeling, and experiments. We find that head mesodermal cells in culture move in random directions as individuals and move faster in the presence of neural crest cells. In vivo, mesodermal cells migrate in a directed manner and maintain neighbor relationships; neural crest cells travel through the mesoderm at a faster speed. The mesoderm grows with a non-uniform spatio-temporal profile determined by BrdU labeling during the period of faster and more-directed neural crest collective migration through this domain. We use computer simulations to probe the robustness of neural crest stream formation by varying the spatio-temporal growth profile of the mesoderm. We follow this with experimental manipulations that either stop mesoderm growth or prevent neural crest migration and observe changes in the non-manipulated cell population, implying a dynamic feedback between tissue growth and neural crest cell signaling to confer robustness to the system. Overall, we present a novel descriptive analysis of mesoderm and neural crest cell dynamics that reveals the coordination and co-dependence of these two cell populations during head morphogenesis.
Topics: Animals; Cell Division; Cell Movement; Cells, Cultured; Chick Embryo; Chickens; Computer Simulation; Coturnix; Ectoderm; Head; Mesoderm; Models, Biological; Morphogenesis; Neural Crest; Neural Tube; Time-Lapse Imaging
PubMed: 32084354
DOI: 10.1016/j.ydbio.2020.02.010 -
Circulation Research Aug 2021
Topics: Heart; Mesoderm
PubMed: 34351798
DOI: 10.1161/CIRCRESAHA.121.319735 -
PloS One 2022Mesoderm specific transcript (Mest)/paternally expressed gene-1 (Peg1) is an imprinted gene expressed predominantly from the paternal allele. Aberrations in maternal...
Mesoderm specific transcript (Mest)/paternally expressed gene-1 (Peg1) is an imprinted gene expressed predominantly from the paternal allele. Aberrations in maternal behavior were previously reported in a Mest global knockout mouse (Mesttm1Masu). In this study, we performed in-depth social and maternal behavioral testing in a mouse model of Mest inactivation developed in our laboratory (Mesttm1.2Rkz). Mice with paternal allele inactivation (MestpKO) did not show anxiety after testing in the elevated plus maze, open field trial, and marble burying; nor depression-like behaviors in the tail suspension test. MestpKO showed normal social behaviors and memory/cognition in the three-chamber box test and the novel object recognition test, respectively. Primiparous MestpKO and MestgKO (biallelic Mest inactivation) female mice exhibited normal nest building and maternal behavior; and, virgin MestpKO and MestgKO female mice showed normal maternal instinct. Analyses of gene expression in adult hypothalamus, embryonic day 14.5 whole brain and adult whole brain demonstrated full abrogation of Mest mRNA in MestpKO and MestgKO mice with no effect on miR-335 expression. Our data indicates no discernible impairments in object recognition memory, social behavior or maternal behavior resulting from loss of Mest. The basis for the differences in maternal phenotypic behaviors between Mesttm1Masu and Mesttm1.2Rkz is not known.
Topics: Alleles; Animals; Female; Genomic Imprinting; Maternal Behavior; Mesoderm; Mice; Proteins
PubMed: 35867696
DOI: 10.1371/journal.pone.0271913 -
Neuro-mesodermal assembloids recapitulate aspects of peripheral nervous system development in vitro.Stem Cell Reports May 2023Here we describe a novel neuro-mesodermal assembloid model that recapitulates aspects of peripheral nervous system (PNS) development such as neural crest cell (NCC)...
Here we describe a novel neuro-mesodermal assembloid model that recapitulates aspects of peripheral nervous system (PNS) development such as neural crest cell (NCC) induction, migration, and sensory as well as sympathetic ganglion formation. The ganglia send projections to the mesodermal as well as neural compartment. Axons in the mesodermal part are associated with Schwann cells. In addition, peripheral ganglia and nerve fibers interact with a co-developing vascular plexus, forming a neurovascular niche. Finally, developing sensory ganglia show response to capsaicin indicating their functionality. The presented assembloid model could help to uncover mechanisms of human NCC induction, delamination, migration, and PNS development. Moreover, the model could be used for toxicity screenings or drug testing. The co-development of mesodermal and neuroectodermal tissues and a vascular plexus along with a PNS allows us to investigate the crosstalk between neuroectoderm and mesoderm and between peripheral neurons/neuroblasts and endothelial cells.
Topics: Humans; Endothelial Cells; Neural Stem Cells; Schwann Cells; Axons; Mesoderm; Neural Crest
PubMed: 37084722
DOI: 10.1016/j.stemcr.2023.03.012 -
Cell Jan 2017The immune system safeguards organ integrity by employing a balancing act of inflammatory and immunosuppressive mechanisms designed to neutralize foreign invaders and... (Review)
Review
The immune system safeguards organ integrity by employing a balancing act of inflammatory and immunosuppressive mechanisms designed to neutralize foreign invaders and resolve injury. Maintaining or restoring a state of immune homeostasis is particularly challenging at barrier sites where constant exposure to immunogenic environmental agents may induce destructive inflammation. Recent studies underscore the role of epithelial and mesenchymal barrier cells in regulating immune cell function and local homeostatic and inflammatory responses. Here, we highlight immunoregulatory circuits engaging epithelial and mesenchymal cells in the intestine, airways, and skin and discuss how immune communications with hematopoietic cells and the microbiota orchestrate local immune homeostasis and inflammation.
Topics: Animals; Epithelial Cells; Epithelium; Homeostasis; Humans; Infections; Inflammation; Intestines; Mesoderm; Respiratory System
PubMed: 28129537
DOI: 10.1016/j.cell.2016.11.040 -
Development (Cambridge, England) Feb 2021The generation of the components that make up the embryonic body axis, such as the spinal cord and vertebral column, takes place in an anterior-to-posterior... (Review)
Review
The generation of the components that make up the embryonic body axis, such as the spinal cord and vertebral column, takes place in an anterior-to-posterior (head-to-tail) direction. This process is driven by the coordinated production of various cell types from a pool of posteriorly-located axial progenitors. Here, we review the key features of this process and the biology of axial progenitors, including neuromesodermal progenitors, the common precursors of the spinal cord and trunk musculature. We discuss recent developments in the production of axial progenitors and their potential implications in disease modelling and regenerative medicine.
Topics: Animals; Biology; Body Patterning; Ectoderm; Endoderm; Gastrulation; Gene Expression Regulation, Developmental; Germ Layers; Humans; In Vitro Techniques; Mesoderm; Muscle, Skeletal; Stem Cells
PubMed: 33593754
DOI: 10.1242/dev.180612