scholarly journals Spatiotemporal contribution of neuromesodermal progenitor-derived neural cells in the elongation of developing mouse spinal cord

2020 ◽  
Author(s):  
Mohammed R Shaker ◽  
Ju-Hyun Lee ◽  
Kyung Hyun Kim ◽  
Veronica Jihyun Kim ◽  
Joo Yeon Kim ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neural Tube ◽  
Dorsal Side ◽  
Lineage Tracing ◽  
The Body ◽  
Lumbar Spinal Cord ◽  
Genetic Lineage ◽  
Mouse Development ◽  
Axial Elongation

ABSTRACTDuring vertebrate development, the posterior end of the embryo progressively elongates in a head-to-tail direction to form the body plan. Recent lineage tracing experiments revealed that bi-potent progenitors, called neuromesodermal progenitors (NMPs), produce caudal neural and mesodermal tissues during axial elongation. However, their precise location and contribution to spinal cord development remain elusive. Here we used NMP-specific markers (Sox2 and BraT) and a genetic lineage tracing system to localize NMP progeny in vivo. NMPs were initially located at the tail tip, but were later found in the caudal neural tube, which is a unique feature of mouse development. In the neural tube, they produced neural stem cells (NSCs) and contributed to the spinal cord gradually along the AP axis during axial elongation. Interestingly, NMP-derived NSCs preferentially contributed to the ventral side first and later to the dorsal side at the lumbar spinal cord level, which may be associated with atypical junctional neurulation in mice. Our current observations detail the contribution of NMP progeny to spinal cord elongation and provide insights into how different species uniquely execute caudal morphogenesis.

scholarly journals Direct neuronal reprogramming by temporal identity factors

2021 ◽  
Author(s):  
Camille Boudreau-Pinsonneault ◽  
Awais Javed ◽  
Michel Fries ◽  
Pierre Mattar ◽  
Michel Cayouette
Keyword(s):  
Gene Expression ◽  
Expression System ◽  
Lineage Tracing ◽  
Developmental Competence ◽  
Rapid Screening ◽  
Mouse Retina ◽  
Genetic Lineage ◽  
Differentiated Cells ◽  
Temporal Identity

Temporal identity factors are sufficient to reprogram developmental competence of neural progenitors, but whether they could also reprogram the identity of fully differentiated cells is unknown. To address this question, we designed a conditional gene expression system combined with genetic lineage tracing that allows rapid screening of potential reprogramming factors in the mouse retina. Using this assay, we report that co-expression of the early temporal identity transcription factor Ikzf1, together with Ikzf4, another Ikaros family member, is sufficient to directly convert adult Muller glial cells into neuron-like cells in vivo, without inducing a proliferative progenitor state. scRNA-seq analysis shows that the reprogrammed cells share some transcriptional signatures with both cone photoreceptors and bipolar cells. Furthermore, we show that co-expression of Ikzf1 and Ikzf4 can reprogram mouse embryonic fibroblasts to induced neurons by remodeling chromatin and promoting a neuronal gene expression program. This work uncovers general neuronal reprogramming properties for temporal identity factors in differentiated cells, opening new opportunities for cell therapy development.

scholarly journals Repopulating Kupffer Cells Originate Directly from Hematopoietic Stem Cells

2021 ◽  
Author(s):  
Xu Fan ◽  
Pei Lu ◽  
Xianghua Cui ◽  
Peng Wu ◽  
Weiran Lin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Kupffer Cells ◽  
Lineage Tracing ◽  
Genetic Lineage ◽  
Fate Mapping ◽  
Monocytic Cell ◽  
Hematopoietic Stem ◽  
Cellular Origin

Abstract Kupffer cells (KCs) originate from yolk sac progenitors before birth, but the origin of repopulating KCs in adult remains unclear. In current study, we firstly traced the fate of preexisting KCs and that of monocytic cells with tissue-resident macrophage-specific and monocytic cell-specific fate mapping mouse models, respectively, and found no evidences that repopulating KCs originate from preexisting KCs or MOs. Secondly, we performed genetic lineage tracing to determine the type of progenitor cells involved in response to KC depletion in mice, and found that in response to KC depletion, hematopoietic stem cells (HSCs) proliferated in the bone marrow, mobilized into the blood, adoptively transferred into the liver and differentiated into KCs. Finally, we traced the fate of HSCs in a HSC-specific fate-mapping mouse model, in context of chronic liver inflammation induced by repeated carbon tetrachloride treatment, and confirmed that repopulating KCs originated directly from HSCs. Taken together, these findings provided in vivo fate-mapping evidences that repopulating KCs originate directly from hematopoietic stem cells, which present a completely novel understanding of the cellular origin of repopulating Kupffer Cells and shedding light on the divergent roles of KCs in liver homeostasis and diseases.

scholarly journals Spinal Cord Modular Organization and Rhythm Generation: An NMDA Iontophoretic Study in the Frog

1998 ◽  
Vol 80 (5) ◽  
pp. 2323-2339 ◽  
Author(s):  
Philippe Saltiel ◽  
Matthew C. Tresch ◽  
Emilio Bizzi
Keyword(s):  
Spinal Cord ◽  
Isometric Force ◽  
Pattern Generation ◽  
The Body ◽  
Lumbar Spinal Cord ◽  
Modular Organization ◽  
Rhythmic Pattern ◽  
Rhythm Generation ◽  
Force Output ◽  
Electrical Microstimulation

Saltiel, Philippe, Matthew C. Tresch, and Emilio Bizzi. Spinal cord modular organization and rhythm generation: a NMDA iontophoretic study in the frog. J. Neurophysiol. 80: 2323–2339, 1998. Previous work using electrical microstimulation has suggested the existence of modules subserving limb posture in the spinal cord. In this study, the question of modular organization was reinvestigated with the more selective method of chemical microstimulation. N-methyl-d-aspartate (NMDA) iontophoresis was applied to 229 sites of the lumbar spinal cord gray while monitoring the isometric force output of the ipsilateral hindlimb at the ankle. A force response was elicited from 69 sites. At 18 of these sites, tonic forces were generated and rhythmic forces at 44. In the case of tonic forces, their directions clustered along four orientations: lateral extension, rostral flexion, adduction, and caudal extension. For the entire set of forces (tonic and rhythmic), the same clusters of orientations were found with the addition of a cluster directed as a flexion toward the body. This distribution of force orientations was quite comparable to that obtained with electrical stimulation at the same sites. The map of tonic responses revealed a topographic organization; each type of force orientation was elicited from sites that grouped together in zones at distinct rostrocaudal and depth locations. In the case of rhythmic sequences of force orientations, some were distinctly more common, whereas others were rarely elicited by NMDA. Mapping of the most common rhythms showed that each was elicited from two or three regions of the cord. These regions were close in location to the tonic regions that produced those forces that represented components specific to that rhythm. There was an additional caudal region from which the different rhythms also could be elicited. Taken together, these results support the concept of a modular organization of the motor system in the frog's spinal cord and delineate the topography of these modules. They also suggest that these modules are used by the circuitry underlying rhythmic pattern generation by the spinal cord.

scholarly journals Perivascular-Derived Mesenchymal Stem Cells

2019 ◽  
Vol 98 (10) ◽  
pp. 1066-1072 ◽  
Author(s):  
V. Yianni ◽  
P.T. Sharpe
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dental Pulp ◽  
Molecular Mechanisms ◽  
Lineage Tracing ◽  
Specific Gene ◽  
Genetic Lineage ◽  
Differentiation Potential

Cells have been identified in postnatal tissues that, when isolated from multiple mesenchymal compartments, can be stimulated in vitro to give rise to cells that resemble mature mesenchymal phenotypes, such as odontoblasts, osteoblasts, adipocytes, and myoblasts. This has made these adult cells, collectively called mesenchymal stem cells (MSCs), strong candidates for fields such as tissue engineering and regenerative medicine. Based on evidence from in vivo genetic lineage–tracing studies, pericytes have been identified as a source of MSC precursors in vivo in multiple organs, in response to injury or during homeostasis. Questions of intense debate and interest in the field of tissue engineering and regenerative studies include the following: 1) Are all pericytes, irrespective of tissue of isolation, equal in their differentiation potential? 2) What are the mechanisms that regulate the differentiation of MSCs? To gain a better understanding of the latter, recent work has utilized ChIP-seq (chromatin immunoprecipitation followed by sequencing) to reconstruct histone landscapes. This indicated that for dental pulp pericytes, the odontoblast-specific gene Dspp was found in a transcriptionally permissive state, while in bone marrow pericytes, the osteoblast-specific gene Runx2 was primed for expression. RNA sequencing has also been utilized to further characterize the 2 pericyte populations, and results highlighted that dental pulp pericytes are already precommitted to an odontoblast fate based on enrichment analysis indicating overrepresentation of key odontogenic genes. Furthermore, ChIP-seq analysis of the polycomb repressive complex 1 component RING1B indicated that this complex is likely to be involved in inhibiting inappropriate differentiation, as it localized to a number of loci of key transcription factors that are needed for the induction of adipogenesis, chondrogenesis, or myogenesis. In this review, we highlight recent data elucidating molecular mechanisms that indicate that pericytes can be tissue-specific precommitted MSC precursors in vivo and that this precommitment is a major driving force behind MSC differentiation.

Pattern of Motor Coordination Underlying Backward Swimming in the Lamprey

2006 ◽  
Vol 96 (1) ◽  
pp. 451-460 ◽  
Author(s):  
Salma S. Islam ◽  
Pavel V. Zelenin ◽  
Grigori N. Orlovsky ◽  
Sten Grillner ◽  
Tatiana G. Deliagina
Keyword(s):  
Spinal Cord ◽  
Motor Coordination ◽  
Anterior Part ◽  
Dorsal Side ◽  
The Body ◽  
Large Area ◽  
Lower Vertebrate ◽  
Complete Transection ◽  
Lateral Body ◽  
Propagating Waves

The main form of locomotion in the lamprey (a lower vertebrate, cyclostome) is forward swimming (FS) based on periodical waves of lateral body flexion propagating from head to tail. The lamprey is also capable of backward swimming (BS). Here we describe the kinematical and electromyographic (EMG) pattern of BS, as well as the effects on this pattern exerted by different lesions of the spinal cord. The BS was evoked by tactile stimulation of a large area in the anterior part of the body. Swimming was attributed to the waves of lateral body undulations propagating from tail to head. The EMG bursts on the two sides alternated, and the EMG in more caudal segments led in phase the EMG in more rostral segments. Main kinematical characteristics of BS strongly differed from those of FS: the amplitude of undulations was much larger and their frequency lower. Also, the maintenance of the dorsal-side-up body orientation ascribed to vestibular postural reflexes (typical for FS) was not observed during BS. A complete transection of the spinal cord did not abolish the generation of forward-propagating waves rostral to the lesion. After a lateral hemisection of the spinal cord, the BS pattern persisted on both sides rostral to the lesion; caudal to the lesion, it was present on the intact side and reduced or abolished on the lesioned side. The role of the spinal cord in generation of different forms of undulatory locomotion (FS and BS) is discussed.

scholarly journals Evidence for minimal cardiogenic potential of Sca-1 positive cells in the adult mouse heart

2018 ◽  
Author(s):  
Lauren E. Neidig ◽  
Florian Weinberger ◽  
Nathan J. Palpant ◽  
John Mignone ◽  
Amy M. Martinson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Mouse Model ◽  
Lineage Tracing ◽  
Mouse Heart ◽  
Genetic Lineage ◽  
Adult Heart ◽  
New Therapeutic Approaches ◽  
Genetic Lineage Tracing

ABSTRACTBackgroundDespite modern pharmacotherapy, heart failure remains a major medical burden. The heart has a limited regenerative capacity, and bolstering regeneration might represent new therapeutic approaches for heart failure patients. Various progenitor cells in the heart have been proposed to have cardiomyogenic properties, but this evidence is based mostly on cell culture and transplantation studies. One population of interest is characterized by the expression of Stem Cell Antigen-1 (Sca-1). Here we tested the hypothesis that Sca-1+cells are endogenous progenitors for cardiomyocytes in the adult heart.MethodsWe evaluated the innate cardiogenic potential of Sca-1+cellsin vivoby generating a novel mouse model to genetically lineage-trace the fate of Sca-1 expressing cells. This was accomplished by introducing a tamoxifen-inducible Cre-recombinase into the Sca-1 locus (Sca-1mCm/+). Crossing this mouse line to a Cre-dependent tdTomato reporter line allowed for genetic lineage-tracing of endogenous Sca-1+cells (Sca-1mCmR26tdTomato). The frequency of Sca-1+cardiomyocytes was quantified from dispersed cell preparations and confirmed by in situ histology.ResultsWe validated the genetic lineage tracing mouse model in bone marrow and heart. Unlike previous publications suggesting significant cardiogenic potential, we found that less than 0.02% of cardiomyocytes per year were derived from Sca-1+cells in the adult heart under homeostatic conditions. At six months after myocardial infarction, we found less than 0.01% of cardiomyocytes were derived from Sca-1+cells.ConclusionOur results show that Sca-1+cells in the adult heart have minimal cardiogenic potential under homeostatic conditions or in response to myocardial infarction.

scholarly journals FZD10 regulates cell proliferation and mediates Wnt1 induced neurogenesis in the developing spinal cord

2019 ◽  
Author(s):  
Abdulmajeed Fahad Alrefaei ◽  
Andrea E. Münsterberg ◽  
Grant N. Wheeler
Keyword(s):  
Spinal Cord ◽  
Cell Proliferation ◽  
Neural Tube ◽  
Spinal Cord Development ◽  
Dorsal Neural Tube ◽  
Wnt Ligands ◽  
Frizzled Receptors ◽  
Developmental Contexts ◽  
Developing Spinal Cord

AbstractWnt/FZD signalling activity is required for spinal cord development, including the dorsal-ventral patterning of the neural tube, where it affects proliferation and specification of neurons. Wnt ligands initiate canonical, β-catenin-dependent, signaling by binding to Frizzled receptors. However, in many developmental contexts the cognate FZD receptor for a particular Wnt ligand remains to be identified. Here, we characterized FZD10 expression in the dorsal neural tube where it overlaps with both Wnt1 and Wnt3a, as well as markers of dorsal progenitors and interneurons. We show FZD10 expression is sensitive to Wnt1, but not Wnt3a expression, and FZD10 plays a role in neural tube patterning. Knockdown approaches show that Wnt1 induced ventral expansion of dorsal neural markes, Pax6 and Pax7, requires FZD10. In contrast, Wnt3a induced dorsalization of the neural tube is not affected by FZD10 knockdown. Gain of function experiments show that FZD10 is not sufficient on its own to mediate Wnt1 activity in vivo. Indeed excess FZD10 inhibits the dorsalizing activity of Wnt1. However, addition of the Lrp6 co-receptor dramatically enhances the Wnt1/FZD10 mediated activation of dorsal markers. This suggests that the mechanism by which Wnt1 regulates proliferation and patterning in the neural tube requires both FZD10 and Lrp6.

scholarly journals In vivo and in vitro models of traumatic injuries of the spinal cord

2017 ◽  
Vol 5 (1) ◽  
pp. 87-93
Author(s):  
O. Rybachuk ◽  
I. Arkhypchuk ◽  
Yu. Lazarenko
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Traffic Accidents ◽  
Experimental Models ◽  
The Body ◽  
Nerve Tissue ◽  
Economic Losses ◽  
Cord Injury

In recent years, there is a growing interest in the mechanisms of regeneration of damaged nerve tissue, including the spinal cord, as its injuries are quite common due to traffic accidents, industrial injuries and military actions. Damage to the spinal cord results in the loss of functional activity of the body below the injury site, which affects person’s ability to self-service and significantly reduces its efficiency. The effects of spinal injuries annually cause significant social and economic losses worldwide, including Ukraine. The development of new treatments for pathologies of the central nervous system requires mandatory pre-testing of their effectiveness in experiments in vitro and in vivo. Therefore, searching and creation of optimal animal model of spinal cord injury is in order to it meets most complete picture of the damage characteristic of real conditions in humans. This is an important task of modern neurophysiology. Such models can be used, primarily, for a more detailed clarification of the pathogenesis of all levels of nerve tissue damage and research of its own recovery potential by endogenous reparation mechanisms. In addition, experimental models allow to estimate the safety and predict the effectiveness of various therapeutic approaches to spinal cord injury.

scholarly journals Pericyte-derived fibrotic scarring is conserved across diverse central nervous system lesions

2020 ◽  
Author(s):  
David O. Dias ◽  
Jannis Kalkitsas ◽  
Yildiz Kelahmetoglu ◽  
Cynthia P. Estrada ◽  
Jemal Tatarishvili ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Mouse Models ◽  
Stromal Cells ◽  
Primary Source ◽  
Lineage Tracing ◽  
Fibrotic Tissue ◽  
Cord Injury

AbstractFibrotic scar tissue limits central nervous system regeneration in adult mammals. The extent of fibrotic tissue generation and distribution of stromal cells across different lesions in the brain and spinal cord has not been systematically investigated in mice and humans. Furthermore, it is unknown whether scar-forming stromal cells have the same origin throughout the central nervous system and in different types of lesions. In the current study, we compared fibrotic scarring in human pathological tissue and corresponding mouse models of penetrating and non-penetrating spinal cord injury, traumatic brain injury, ischemic stroke, multiple sclerosis and glioblastoma. We show that the extent and distribution of stromal cells are specific to the type of lesion and, in most cases, similar between mice and humans. Employing in vivo lineage tracing, we report that in all mouse models developing fibrotic tissue, the primary source of scar-forming fibroblasts is a discrete subset of perivascular cells, termed type A pericytes.We uncover pericyte-derived fibrosis as a conserved mechanism that may be explored as a therapeutic target to improve recovery after central nervous system lesions.

scholarly journals Seamless Genetic Recording of Transiently Activated Mesenchymal Gene Expression in Endothelial Cells During Cardiac Fibrosis

Circulation ◽  
2021 ◽  
Author(s):  
Shaohua Zhang ◽  
Yan Li ◽  
Xiuzhen Huang ◽  
Kuo Liu ◽  
Qing-Dong Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Cardiac Fibrosis ◽  
Marker Gene ◽  
Lineage Tracing ◽  
Genetic Lineage ◽  
Mesenchymal Transition ◽  
Heart Injury

Background: Cardiac fibrosis is a lethal outcome of excessive formation of myofibroblasts that are scar-forming cells accumulated after heart injury. It has been reported that cardiac endothelial cells (ECs) contribute to a substantial portion of myofibroblasts through EndoMT. Recent lineage tracing studies demonstrate that myofibroblasts are derived from expansion of resident fibroblasts rather than from transdifferentiation of ECs. However, it remains unknown whether ECs can transdifferentiate into myofibroblasts reversibly or EndoMT genes were just transiently activated in ECs during cardiac fibrosis. Methods: By using the dual recombination technology based on Cre-loxP and Dre-rox, we generated a genetic lineage tracing system for tracking EndoMT in cardiac ECs. We used it to examine if there is transiently activated mesenchymal gene expression in ECs during cardiac fibrosis. Activation of the broadly used marker gene in myofibroblasts, αSMA, and the transcription factor that induces epithelial to mesenchymal transition (EMT), Zeb1, was examined. Results: The genetic system enables continuous tracing of transcriptional activity of targeted genes in vivo . Our genetic fate mapping results revealed that a subset of cardiac ECs transiently expressed αSMA and Zeb1 during embryonic valve formation and transdifferentiated into mesenchymal cells through EndoMT. Nonetheless, they did not contribute to myofibroblasts; nor transiently expressed αSMA or Zeb1 after heart injury. Instead, expression of αSMA was activated in resident fibroblasts during cardiac fibrosis. Conclusions: Mesenchymal gene expression is activated in cardiac ECs through EndoMT in the developing heart; but ECs do not transdifferentiate into myofibroblasts, nor transiently express some known mesenchymal genes during homeostasis and fibrosis in the adult heart. Resident fibroblasts that are converted to myofibroblasts by activating mesenchymal gene expression are the major contributors to cardiac fibrosis.

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