Molecular Mechanisms of Plant Regeneration

2019 ◽  
Vol 70 (1) ◽  
pp. 377-406 ◽  
Author(s):  
Momoko Ikeuchi ◽  
David S. Favero ◽  
Yuki Sakamoto ◽  
Akira Iwase ◽  
Duncan Coleman ◽  
...  
Keyword(s):  
Cell Fate ◽  
Molecular Mechanisms ◽  
Normal Development ◽  
Somatic Cells ◽  
Cell Fates ◽  
Developmental Programs ◽  
Hormonal Responses ◽  
Wound Stress ◽  
Directional Transport

Plants reprogram somatic cells following injury and regenerate new tissues and organs. Upon perception of inductive cues, somatic cells often dedifferentiate, proliferate, and acquire new fates to repair damaged tissues or develop new organs from wound sites. Wound stress activates transcriptional cascades to promote cell fate reprogramming and initiate new developmental programs. Wounding also modulates endogenous hormonal responses by triggering their biosynthesis and/or directional transport. Auxin and cytokinin play pivotal roles in determining cell fates in regenerating tissues and organs. Exogenous application of these plant hormones enhances regenerative responses in vitro by facilitating the activation of specific developmental programs. Many reprogramming regulators are epigenetically silenced during normal development but are activated by wound stress and/or hormonal cues.

Advances and Challenges in Kidney Organoids

2021 ◽  
Vol 16 ◽  
Author(s):  
Vikram Sabapathy ◽  
Gabrielle Costlow ◽  
Rajkumar Venkatadri ◽  
Murat Dogan ◽  
Sanjay Kumar ◽  
...  
Keyword(s):  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Complex Structures ◽  
Cell Culture Systems ◽  
Epigenetic Signatures ◽  
Kidney Organoids

: The advent of organoids has renewed researcher's interest in in vitro cell culture systems. A wide variety of protocols, primarily utilizing pluripotent stem cells, are under development to improve organoid generation to mimic organ development. The complexity of organoids generated is greatly influenced based on the method used. Understanding the process of kidney organoid formation gives developmental insights into how renal cells form, mature, and interact with the adjacent cells to form specific spatiotemporal structural patterns. This knowledge can bridge the gaps in understanding in vivo renal developmental processes. Evaluating genetic and epigenetic signatures in specialized cell types can help interpret the molecular mechanisms governing cell fate. In addition, development in single-cell RNA sequencing and 3D bioprinting and microfluidic technologies has led to better identification and understanding of a variety of cell types during differentiation and designing of complex structures to mimic the conditions in vivo. While several reviews have highlighted the application of kidney organoids, there is no comprehensive review of various methodologies specifically focusing on the kidney organoids. This review summarizes the updated differentiation methodologies, applications, and challenges associated with kidney organoids. Here we have comprehensively collated all the different variables influencing the organoid generation.

scholarly journals Pluripotency and Epigenetic Factors in Mouse Embryonic Stem Cell Fate Regulation

2015 ◽  
Vol 35 (16) ◽  
pp. 2716-2728 ◽  
Author(s):  
Lluis Morey ◽  
Alexandra Santanach ◽  
Luciano Di Croce
Keyword(s):  
Cell Fate ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Basic Research ◽  
Cell Types ◽  
Pluripotency Factors ◽  
Perfect System

Embryonic stem cells (ESCs) are characterized by their ability to self-renew and to differentiate into all cell types of a given organism. Understanding the molecular mechanisms that govern the ESC state is of great interest not only for basic research—for instance, ESCs represent a perfect system to study cellular differentiationin vitro—but also for their potential implications in human health, as these mechanisms are likewise involved in cancer progression and could be exploited in regenerative medicine. In this minireview, we focus on the latest insights into the molecular mechanisms mediated by the pluripotency factors as well as their roles during differentiation. We also discuss recent advances in understanding the function of the epigenetic regulators, Polycomb and MLL complexes, in ESC biology.

scholarly journals The Role of Prep1 in the Regulation of Mesenchymal Stromal Cells

2019 ◽  
Vol 20 (15) ◽  
pp. 3639 ◽  
Author(s):  
Giorgia Maroni ◽  
Daniele Panetta ◽  
Raffaele Luongo ◽  
Indira Krishnan ◽  
Federica La Rosa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Fate ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Gene Dosage ◽  
Homeobox Gene ◽  
Fate Decision

Molecular mechanisms governing cell fate decision events in bone marrow mesenchymal stromal cells (MSC) are still poorly understood. Herein, we investigated the homeobox gene Prep1 as a candidate regulatory molecule, by adopting Prep1 hypomorphic mice as a model to investigate the effects of Prep1 downregulation, using in vitro and in vivo assays, including the innovative single cell RNA sequencing technology. Taken together, our findings indicate that low levels of Prep1 are associated to enhanced adipogenesis and a concomitant reduced osteogenesis in the bone marrow, suggesting Prep1 as a potential regulator of the adipo-osteogenic differentiation of mesenchymal stromal cells. Furthermore, our data suggest that in vivo decreased Prep1 gene dosage favors a pro-adipogenic phenotype and induces a “browning” effect in all fat tissues.

scholarly journals Morphogen And Community Effects Determine Cell Fates In Response To BMP4 Signaling In Human Embryonic Stem Cells

2017 ◽  
Author(s):  
Anastasiia Nemashkalo ◽  
Albert Ruzo ◽  
Idse Heemskerk ◽  
Aryeh Warmflash
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Fate ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Culture Conditions ◽  
Community Effects ◽  
Cell Fates ◽  
Standard Culture

AbstractParacrine signals maintain developmental states and create cell-fate patterns in vivo, and influence differentiation outcomes in human embryonic stem cells (hESCs) in vitro. Systematic investigation of morphogen signaling is hampered by the difficulty of disentangling endogenous signaling from experimentally applied ligands. Here, we grow hESCs in micropatterned colonies of 1-8 cells (“μColonies”) to quantitatively investigate paracrine signaling and the response to external stimuli. We examine BMP4-mediated differentiation in μColonies and standard culture conditions and find that in μColonies, above a threshold concentration, BMP4 gives rise to only a single cell fate, contrary to its role as a morphogen in other developmental systems. Under standard culture conditions, BMP4 acts as morphogen, but this effect requires secondary signals and particular cell densities. We further find that a “community effect” enforces a common fate within μColonies both in the state of pluripotency and when cells are differentiated, and that this effect allows more precise response to external signals. Using live cell imaging to correlate signaling histories with cell fates, we demonstrate that interactions between neighbors result in sustained, homogenous signaling necessary for differentiation.Summary StatementWe quantitatively examined signaling and differentiation in hESC colonies of varying size treated with BMP4. We show that secondary signals result in morphogen and community effects that determine cell fates.

Abstract 141: Histone Methyltransferase Setdb2 is important for miRNA mediated cardiac reprogramming

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Imke Kirste ◽  
Tilanthi M Jayawardena ◽  
J. A Payne ◽  
Victor J Dzau ◽  
Maria Mirotsou
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Cardiac Tissue ◽  
Chromatin Modification ◽  
Jak Inhibitor ◽  
Daunting Challenge

Rationale: Regeneration of damaged cardiac tissue after injury presents a daunting challenge in cardiovascular medicine. Recent developments in reprogramming of somatic cells directly to cells of other lineages have raised the possibility of using this approach for cardiac regenerative therapy. Our group recently demonstrated successful miRNA mediated cardiac reprogramming in vitro and in vivo using a combination of miRNAs 1, 133, 206 and 499. Although, the molecular mechanisms underlying miRNA mediated fibroblast reprogramming to cardiomyocytes are yet unknown, accumulating evidence suggest that reprogramming acts through distinct phases and that histone modifications play an important role in these processes. Objective: Identify key genes involved in initiating miRNA mediated reprogramming via histone modifications. Methods and Results: For this, we analyzed the expression levels of 81 different genes involved in chromatin modification 4 days after miRNA transfection using PCR arrays. This analysis revealed that 6 of the 81 tested genes showed differential gene expression (≤-1.5-fold and p <0.02). JAK inhibitor-1 treatment, known for increasing reprogramming efficiency, further enhanced gene expression changes in 5 of these 6 genes. Setdb2, an H3K9 methyltransferase, was one of the most down-regulated targets 4 days after miRNA transfection (-1.4 fold, p<0.001). This effect was enhanced further when miRNAs were combined with the JAK inhibitor-1 (-2.6 fold, p<0.001). Silencing of Setdb2 using siRNAs further accentuated miRNA cardiac reprogramming as measured by cardiac transcription factor expression at 3 days and 6 days post treatment. Similar trends were observed by FACS analysis detecting increased percentage of αMHC-positive cells in siRNA treated fibroblasts compared to control treated only with the miRNA combination. Interestingly, our data showed that Setdb2 silencing alone was sufficient to initiate cardiac reprogramming, suggesting that Setdb2 might play a crucial role in defining cardiac cell fate. Conclusion: In conclusion our results indicate that Setdb2 down-regulation plays an important role in the direct reprogramming of fibroblasts to cardiomyocyte-like cells.

Transduction mechanisms for gonadotrophin-induced oocyte maturation in mammals

Zygote ◽  
1994 ◽  
Vol 2 (4) ◽  
pp. 347-349 ◽  
Author(s):  
Mauro Mattioli
Keyword(s):  
Oocyte Maturation ◽  
Normal Development ◽  
Somatic Cells ◽  
Transduction Mechanisms

Although many validated techniques for oocyte maturation in vitro have been developed and eggs with normal development competence can be produced by these methods, the mechnism triggering oocyte maturation in vivo is still poorly understood. Little doubt exists that meiosis is reinitiated in pre-ovlulatory follicles by peak levels of gonadotrophins and that follicle somatic cells are directly involved since no receptors for gonadotrophins have been found on the oolemma.

scholarly journals Emerging role of extracellular vesicles in communication of preimplantation embryos in vitro

2017 ◽  
Vol 29 (1) ◽  
pp. 66 ◽  
Author(s):  
Krishna C. Pavani ◽  
Carmen Alminana ◽  
Eline Wydooghe ◽  
Maaike Catteeuw ◽  
Miguel A. Ramírez ◽  
...  
Keyword(s):  
Embryo Development ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Culture Media ◽  
Somatic Cells ◽  
Indirect Evidence ◽  
Preimplantation Embryos ◽  
Limited Information ◽  
Paracrine Factors

In vitro, efficient communication between mammalian embryos in groups or between embryos and cocultured somatic cells implies that there is a sender, a message and a receiver that is able to decode the message. Embryos secrete a variety of autocrine and paracrine factors and, of these, extracellular vesicles have recently been implicated as putative messengers in embryo–embryo communication, as well as in communication of the embryo with the maternal tract. Extracellular vesicles (EVs) are membrane-bound vesicles that are found in biofluids and in culture media conditioned by the presence of embryos or cells. EVs carry and transfer regulatory molecules, such as microRNAs, mRNAs, lipids and proteins. We conducted a systematic search of the literature to review and present the currently available evidence regarding the possible roles of EVs in in vitro embryo communication and embryo development. It is important to note that there is limited information available on the molecular mechanisms and many of the biologically plausible functions of EVs in embryo communication have not yet been substantiated by conclusive experimental evidence. However, indirect evidence, such as the use of media conditioned by embryos or by somatic cells with improved embryo development as a result, may indicate that EVs can be an important asset for the development of tailor-made media, allowing better embryo development in vitro, even for single embryo culture.

scholarly journals Cellular Programming and Reprogramming: Sculpting Cell Fate for the Production of Dopamine Neurons for Cell Therapy

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Julio C. Aguila ◽  
Eva Hedlund ◽  
Rosario Sanchez-Pernaute
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Dorsal Striatum ◽  
Dopamine Neurons ◽  
Cell Fates ◽  
Intrinsic Factors ◽  
Neuronal Identity ◽  
The Right

Pluripotent stem cells are regarded as a promising cell source to obtain human dopamine neurons in sufficient amounts and purity for cell replacement therapy. Importantly, the success of clinical applications depends on our ability to steer pluripotent stem cells towards the right neuronal identity. In Parkinson disease, the loss of dopamine neurons is more pronounced in the ventrolateral population that projects to the sensorimotor striatum. Because synapses are highly specific, only neurons with this precise identity will contribute, upon transplantation, to the synaptic reconstruction of the dorsal striatum. Thus, understanding the developmental cell program of the mesostriatal dopamine neurons is critical for the identification of the extrinsic signals and cell-intrinsic factors that instruct and, ultimately, determine cell identity. Here, we review how extrinsic signals and transcription factors act together during development to shape midbrain cell fates. Further, we discuss how these same factors can be appliedin vitroto induce, select, and reprogram cells to the mesostriatal dopamine fate.

scholarly journals The Hippo pathway oncoprotein YAP promotes melanoma cell invasion and spontaneous metastasis

2019 ◽  
Author(s):  
Xiaomeng Zhang ◽  
Lie Yang ◽  
Pacman Szeto ◽  
Youfang Zhang ◽  
Kaushalya Amarasinghe ◽  
...  
Keyword(s):  
Cell Fate ◽  
Melanoma Cell ◽  
Cell Invasion ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Expression Profiles ◽  
Hippo Pathway ◽  
Melanoma Metastasis ◽  
The Hippo Pathway

ABSTRACTMelanoma is a deadly form of skin cancer that accounts for a disproportionally large proportion of cancer-related deaths in younger people. Compared to most other skin cancers, a feature of melanoma is its high metastatic capacity, although molecular mechanisms that confer this are not well understood. The Hippo pathway is a key regulator of organ growth and cell fate that is deregulated in many cancers. To analyse the Hippo pathway in cutaneous melanoma, we generated a transcriptional signature of pathway activity in melanoma cells. Hippo-mediated transcriptional activity varied in melanoma cell lines but failed to cluster with known genetic drivers of melanomagenesis such as BRAF and NRAS mutation status. Instead, it correlated strongly with published gene expression profiles linked to melanoma cell invasiveness. Consistent with this, the central Hippo oncogene, YAP, was both necessary and sufficient for melanoma cell invasion in vitro. In in vivo murine studies, YAP promoted spontaneous melanoma metastasis, whilst the growth of YAP-expressing primary tumours was impeded. Finally, we identified the YAP target genes AXL, THBS1 and CYR61 as key mediators of YAP-induced melanoma cell invasion. These data suggest that the Hippo pathway is a critical regulator of melanoma metastasis.

Germ cells of the mammalian female: A limited or renewable resource?

2021 ◽  
Author(s):  
Mathilde Hainaut ◽  
Hugh J Clarke
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Germ Cells ◽  
Germ Line ◽  
Marker Gene ◽  
Somatic Cells ◽  
Renewable Resource ◽  
Weight Of Evidence ◽  
Fetal Life

Abstract In many non-mammalian organisms, a population of germ-line stem cells supports continuing production of gametes during most or all the life of the individual, and germ-line stem cells are also present and functional in male mammals. Traditionally, however, they have been thought not to exist in female mammals, who instead generate all their germ cells during fetal life. Over the last several years, this dogma has been challenged by several reports, while supported by others. We describe and compare these conflicting studies with the aim of understanding how they came to opposing conclusions. We first consider studies that, by examining marker-gene expression, the fate of genetically marked cells, and consequences of depleting the oocyte population, addressed whether ovaries of post-natal females contain oogonial stem cells (OSC) that give rise to new oocytes. We next discuss whether ovaries contain cells that, even if inactive under physiological conditions, nonetheless possess OSC properties that can be revealed through cell-culture. We then examine studies of whether cells harvested after long-term culture of cells obtained from ovaries can, following transplantation into ovaries of recipient females, give rise to oocytes and offspring. Finally, we note studies where somatic cells have been re-programmed to acquire a female germ-cell fate. We conclude that the weight of evidence strongly supports the traditional interpretation that germ-line stem cells do not exist post-natally in female mammals. However, the ability to generate germ cells from somatic cells in vitro establishes a method to generate new gametes from cells of post-natal mammalian females.

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