scholarly journals Mitochondrial Heterogeneity: Evaluating Mitochondrial Subpopulation Dynamics in Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
D. C. Woods
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Cell Biology ◽  
Cell Types ◽  
Cellular Reprogramming ◽  
Cellular Functions ◽  
Technical Advances ◽  
Mitochondrial Heterogeneity ◽  
Key Participants

Although traditionally viewed as the “powerhouse” of the cell, an accruing body of evidence in the rapidly growing field of mitochondrial biology supports additional roles of mitochondria as key participants in a multitude of cellular functions. While it has been well established that mitochondria in different tissues have distinctive ultrastructural features consistent with differential bioenergetic demands, recent and emerging technical advances in flow cytometry, imaging, and “-omics”-based bioinformatics have only just begun to explore the complex and divergent properties of mitochondria within tissues and cell types. Moreover, contemporary studies evaluating the role of mitochondria in pluripotent stem cells, cellular reprogramming, and differentiation point to a potential importance of mitochondrial subpopulations and heterogeneity in the field of stem cell biology. This review assesses the current literature regarding mitochondrial subpopulations within cell and tissue types and evaluates the current understanding of how mitochondrial diversity and heterogeneity might impact cell fate specification in pluripotent stem cells.

scholarly journals The Winding Road of Cardiac Regeneration—Stem Cell Omics in the Spotlight

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 255 ◽  
Author(s):  
Miruna Mihaela Micheu ◽  
Alina Ioana Scarlatescu ◽  
Alexandru Scafa-Udriste ◽  
Maria Dorobantu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Unmet Need ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Great Promise ◽  
Omics Data

Despite significant progress in treating ischemic cardiac disease and succeeding heart failure, there is still an unmet need to develop effective therapeutic strategies given the persistent high-mortality rate. Advances in stem cell biology hold great promise for regenerative medicine, particularly for cardiac regeneration. Various cell types have been used both in preclinical and clinical studies to repair the injured heart, either directly or indirectly. Transplanted cells may act in an autocrine and/or paracrine manner to improve the myocyte survival and migration of remote and/or resident stem cells to the site of injury. Still, the molecular mechanisms regulating cardiac protection and repair are poorly understood. Stem cell fate is directed by multifaceted interactions between genetic, epigenetic, transcriptional, and post-transcriptional mechanisms. Decoding stem cells’ “panomic” data would provide a comprehensive picture of the underlying mechanisms, resulting in patient-tailored therapy. This review offers a critical analysis of omics data in relation to stem cell survival and differentiation. Additionally, the emerging role of stem cell-derived exosomes as “cell-free” therapy is debated. Last but not least, we discuss the challenges to retrieve and analyze the huge amount of publicly available omics data.

scholarly journals Dot1L methyltransferase activity is a barrier to acquisition of pluripotency but not transdifferentiation

2019 ◽  
Author(s):  
Coral K. Wille ◽  
Rupa Sridharan
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Somatic Cells ◽  
Cell Types ◽  
Transcriptional Elongation ◽  
Mrna Levels ◽  
Mesenchymal To Epithelial Transition ◽  
Ipsc Generation ◽  
Induced Pluripotent

ABSTRACTThe ability of pluripotent stem cells to be poised to differentiate into any somatic cell type is partly derived from a unique chromatin structure that is depleted for transcriptional elongation associated epigenetic modifications, primarily H3K79 methylation. Inhibiting the H3K79 methyltransferase, Dot1L, increases the efficiency of reprogramming somatic cells to induced pluripotent stem cells (iPSCs) most potently at the mid-point of the process. Surprisingly, despite the enrichment of H3K79me2 on thousands of actively transcribed genes, Dot1L inhibition (Dot1Li) results in few changes in steady state mRNA levels during reprogramming. Dot1Li spuriously upregulates genes not involved in pluripotency and does not shutdown the somatic program. Depletion of the few genes that are downregulated, such as Nfix, enhances reprogramming efficiency in cooperation with Dot1Li. Contrary to the prevalent view, Dot1Li promotes iPSC generation beyond early phases of reprogramming such as the mesenchymal to epithelial transition and from already epithelial cell types including keratinocytes. Significantly, Dot1L inhibition does not enhance lineage conversion to neurons or muscle cells. Taken together, our results indicate that H3K79me is not a universal barrier of cell fate transitions but specifically protects somatic cells from reverting to the pluripotent state.

scholarly journals Micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterning

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sophie M Morgani ◽  
Jakob J Metzger ◽  
Jennifer Nichols ◽  
Eric D Siggia ◽  
Anna-Katerina Hadjantonakis
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Cell Types ◽  
Mesenchymal Transition ◽  
Fate Specification ◽  
Epiblast Stem Cells

During gastrulation epiblast cells exit pluripotency as they specify and spatially arrange the three germ layers of the embryo. Similarly, human pluripotent stem cells (PSCs) undergo spatially organized fate specification on micropatterned surfaces. Since in vivo validation is not possible for the human, we developed a mouse PSC micropattern system and, with direct comparisons to mouse embryos, reveal the robust specification of distinct regional identities. BMP, WNT, ACTIVIN and FGF directed mouse epiblast-like cells to undergo an epithelial-to-mesenchymal transition and radially pattern posterior mesoderm fates. Conversely, WNT, ACTIVIN and FGF patterned anterior identities, including definitive endoderm. By contrast, epiblast stem cells, a developmentally advanced state, only specified anterior identities, but without patterning. The mouse micropattern system offers a robust scalable method to generate regionalized cell types present in vivo, resolve how signals promote distinct identities and generate patterns, and compare mechanisms operating in vivo and in vitro and across species.

scholarly journals INO80 promotes H2A.Z occupancy to regulate cell fate transition in pluripotent stem cells

2020 ◽  
Author(s):  
Hongyao Yu ◽  
Jiajia Wang ◽  
Brad Lackford ◽  
Brian Bennett ◽  
Jian-liang Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Control Cell ◽  
Epigenetic Mechanism ◽  
Gene Repression ◽  
Gene Promoters ◽  
Cellular Functions ◽  
The Impact

AbstractThe INO80 chromatin remodeler is involved in many chromatin-dependent cellular functions. However, its role in pluripotency and cell fate transition is not fully defined. We examined the impact of Ino80 deletion in the naïve and primed pluripotent stem cells. We found that Ino80 deletion had minimal effect on self-renewal and gene expression in the naïve state, but led to cellular differentiation and de-repression of developmental genes in the transition toward and maintenance of the primed state. Mechanistically, INO80 pre-marked gene promoters that would adopt the H3K4me3 and H3K27me3 bivalent histone modifications. It promoted H2A.Z occupancy at these future bivalent domains to facilitate H3K27me3 installation and maintenance as well as downstream gene repression. Thus, INO80-dependent H2A.Z occupancy is a critical a licensing step for bivalency and poised gene expression in pluripotent stem cells. Our results uncovered an unexpected function of INO80 in H2A.Z deposition and gene repression, and an epigenetic mechanism by which chromatin remodeling, histone variant and modification coordinately control cell fate.

scholarly journals Mitochondrial Biogenesis, Mitochondrial Dynamics, and Mitophagy in the Maturation of Cardiomyocytes

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2463
Author(s):  
Qianqian Ding ◽  
Yanxiang Qi ◽  
Suk-Ying Tsang
Keyword(s):  
Stem Cells ◽  
Mitochondrial Biogenesis ◽  
Pluripotent Stem Cells ◽  
Mitochondrial Dynamics ◽  
Cell Types ◽  
The Other ◽  
Cellular Functions ◽  
Self Renewal ◽  
Mitochondrial Mass ◽  
Excellent Source

Pluripotent stem cells (PSCs) can undergo unlimited self-renewal and can differentiate into all the cell types present in our body, including cardiomyocytes. Therefore, PSCs can be an excellent source of cardiomyocytes for future regenerative medicine and medical research studies. However, cardiomyocytes obtained from PSC differentiation culture are regarded as immature structurally, electrophysiologically, metabolically, and functionally. Mitochondria are organelles responsible for various cellular functions such as energy metabolism, different catabolic and anabolic processes, calcium fluxes, and various signaling pathways. Cells can respond to cellular needs to increase the mitochondrial mass by mitochondrial biogenesis. On the other hand, cells can also degrade mitochondria through mitophagy. Mitochondria are also dynamic organelles that undergo continuous fusion and fission events. In this review, we aim to summarize previous findings on the changes of mitochondrial biogenesis, mitophagy, and mitochondrial dynamics during the maturation of cardiomyocytes. In addition, we intend to summarize whether changes in these processes would affect the maturation of cardiomyocytes. Lastly, we aim to discuss unanswered questions in the field and to provide insights for the possible strategies of enhancing the maturation of PSC-derived cardiomyocytes.

scholarly journals A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0254991
Author(s):  
L. E. Wadkin ◽  
S. Orozco-Fuentes ◽  
I. Neganova ◽  
M. Lako ◽  
N. G. Parker ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mathematical Modelling ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Human Pluripotent Stem Cells ◽  
Logistic Equation ◽  
Mathematical Framework ◽  
Allee Effects ◽  
Modelling Framework

Human pluripotent stem cells (hPSCs) have the potential to differentiate into all cell types, a property known as pluripotency. A deeper understanding of how pluripotency is regulated is required to assist in controlling pluripotency and differentiation trajectories experimentally. Mathematical modelling provides a non-invasive tool through which to explore, characterise and replicate the regulation of pluripotency and the consequences on cell fate. Here we use experimental data of the expression of the pluripotency transcription factor OCT4 in a growing hPSC colony to develop and evaluate mathematical models for temporal pluripotency regulation. We consider fractional Brownian motion and the stochastic logistic equation and explore the effects of both additive and multiplicative noise. We illustrate the use of time-dependent carrying capacities and the introduction of Allee effects to the stochastic logistic equation to describe cell differentiation. We conclude both methods adequately capture the decline in OCT4 upon differentiation, but the Allee effect model has the advantage of allowing differentiation to occur stochastically in a sub-set of cells. This mathematical framework for describing intra-cellular OCT4 regulation can be extended to other transcription factors and developed into predictive models.

scholarly journals Micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterning

2017 ◽  
Author(s):  
Sophie M. Morgani ◽  
Jakob J. Metzger ◽  
Jennifer Nichols ◽  
Eric D. Siggia ◽  
Anna-Katerina Hadjantonakis
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Cell Types ◽  
Mesenchymal Transition ◽  
Fate Specification ◽  
Epiblast Stem Cells

AbstractDuring gastrulation epiblast cells exit pluripotency as they specify and spatially arrange the three germ layers of the embryo. Similarly, human pluripotent stem cells (PSCs) undergo spatially organized fate specification on micropatterned surfaces. Since in vivo validation is not possible for the human, we developed a mouse PSC micropattern system and, with direct comparisons to mouse embryos, reveal the robust specification of distinct regional identities. BMP, WNT, ACTIVIN and FGF directed mouse epiblast-like cells to undergo an epithelial-to-mesenchymal transition and radially pattern posterior mesoderm fates. Conversely, WNT, ACTIVIN and FGF patterned anterior identities, including definitive endoderm. By contrast, epiblast stem cells, a developmentally advanced state, only specified anterior identities, but without patterning. The mouse micropattern system offers a robust scalable method to generate regionalized cell types present in vivo, resolve how signals promote distinct identities and generate patterns, and compare mechanisms operating in vivo and in vitro and across species.

scholarly journals Research and therapy with induced pluripotent stem cells (iPSCs): social, legal, and ethical considerations

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Sharif Moradi ◽  
Hamid Mahdizadeh ◽  
Tomo Šarić ◽  
Johnny Kim ◽  
Javad Harati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Healthy Person ◽  
New Drugs ◽  
Full Potential ◽  
Cell Fate Decisions ◽  
Induced Pluripotent

AbstractInduced pluripotent stem cells (iPSCs) can self-renew indefinitely in culture and differentiate into all specialized cell types including gametes. iPSCs do not exist naturally and are instead generated (“induced” or “reprogrammed”) in culture from somatic cells through ectopic co-expression of defined pluripotency factors. Since they can be generated from any healthy person or patient, iPSCs are considered as a valuable resource for regenerative medicine to replace diseased or damaged tissues. In addition, reprogramming technology has provided a powerful tool to study mechanisms of cell fate decisions and to model human diseases, thereby substantially potentiating the possibility to (i) discover new drugs in screening formats and (ii) treat life-threatening diseases through cell therapy-based strategies. However, various legal and ethical barriers arise when aiming to exploit the full potential of iPSCs to minimize abuse or unauthorized utilization. In this review, we discuss bioethical, legal, and societal concerns associated with research and therapy using iPSCs. Furthermore, we present key questions and suggestions for stem cell scientists, legal authorities, and social activists investigating and working in this field.

scholarly journals bHLH Transcription Factor Math6 Antagonizes TGF-β Signalling in Reprogramming, Pluripotency and Early Cell Fate Decisions

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 529 ◽  
Author(s):  
Satya Srirama Karthik Divvela ◽  
Patrick Nell ◽  
Markus Napirei ◽  
Holm Zaehres ◽  
Jiayu Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Cellular Reprogramming ◽  
Bhlh Transcription Factor ◽  
Tgf Beta ◽  
Cell Fate Decisions ◽  
Helix Loop Helix ◽  
Induced Pluripotent

The basic helix-loop-helix (bHLH) transcription factor Math6 (Atonal homolog 8; Atoh8) plays a crucial role in a number of cellular processes during embryonic development, iron metabolism and tumorigenesis. We report here on its involvement in cellular reprogramming from fibroblasts to induced pluripotent stem cells, in the maintenance of pluripotency and in early fate decisions during murine development. Loss of Math6 disrupts mesenchymal-to-epithelial transition during reprogramming and primes pluripotent stem cells towards the mesendodermal fate. Math6 can thus be considered a regulator of reprogramming and pluripotent stem cell fate. Additionally, our results demonstrate the involvement of Math6 in SMAD-dependent TGF beta signalling. We furthermore monitor the presence of the Math6 protein during these developmental processes using a newly generated Math6Flag-tag mouse. Taken together, our results suggest that Math6 counteracts TGF beta signalling and, by this, affects the initiating step of cellular reprogramming, as well as the maintenance of pluripotency and early differentiation.

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