scholarly journals Mitochondrial Control of Stem Cell State and Fate: Lessons From Drosophila

2021 ◽  
Vol 9 ◽  
Author(s):  
Satish Kumar Tiwari ◽  
Sudip Mandal
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Types ◽  
Extrinsic Factors ◽  
Cell Fate Decisions ◽  
Cell State ◽  
Resident Stem Cells ◽  
Stem Cell State

Over the years, Drosophila has served as a wonderful genetically tractable model system to unravel various facets of tissue-resident stem cells in their microenvironment. Studies in different stem and progenitor cell types of Drosophila have led to the discovery of cell-intrinsic and extrinsic factors crucial for stem cell state and fate. Though initially touted as the ATP generating machines for carrying various cellular processes, it is now increasingly becoming clear that mitochondrial processes alone can override the cellular program of stem cells. The last few years have witnessed a surge in our understanding of mitochondria’s contribution to governing different stem cell properties in their subtissular niches in Drosophila. Through this review, we intend to sum up and highlight the outcome of these in vivo studies that implicate mitochondria as a central regulator of stem cell fate decisions; to find the commonalities and uniqueness associated with these regulatory mechanisms.

scholarly journals Encapsulation and recovery of murine hematopoietic stem and progenitor cells in a thiol-crosslinked maleimide-functionalized gelatin hydrogel

2021 ◽  
Author(s):  
Aidan E Gilchrist ◽  
Julio F. Serrano ◽  
Mai T. Ngo ◽  
Zona Hrnjak ◽  
Sanha Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Click Reaction ◽  
Uv Light ◽  
3D Culture ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem ◽  
Cell Fate Decisions

Biomaterial platforms are an integral part of stem cell biomanufacturing protocols. The collective biophysical, biochemical, and cellular cues of the stem cell niche microenvironment play an important role in regulating stem cell fate decisions. Three-dimensional (3D) culture of stem cells within biomaterials provides a route to present biophysical and biochemical stimuli such as cell-matrix interactions and cell-cell interactions via secreted biomolecules. Herein, we describe a maleimide-functionalized gelatin (GelMAL) hydrogel that can be crosslinked via thiol-Michael addition click reaction for the encapsulation of sensitive stem cell populations. The maleimide functional units along the gelatin backbone enables gelation via the addition of a dithiol crosslinker without requiring external stimuli (e.g., UV light, photoinitiator), reducing reactive oxide species generation. Additionally, the versatility of crosslinker selection enables easy insertion of thiol-containing bioactive or bioinert motifs. Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) were encapsulated in GelMAL, with mechanical properties tuned to mimic the in vivo bone marrow niche. We report insertion of a cleavable peptide crosslinker that can be degraded by the proteolytic action of SortaseA, a mammalian-inert enzyme. Notably, SortaseA exposure preserves stem cell surface markers, an essential metric of hematopoietic activity used in immunophenotyping. This novel GelMAL system enables a route to producing artificial stem cell niches with tunable biophysical properties with intrinsic cell-interaction motifs and orthogonal addition of bioactive crosslinks.

scholarly journals Cellular Population Dynamics Control the Robustness of the Stem Cell Niche

2015 ◽  
Author(s):  
Adam L MacLean ◽  
Paul Kirk ◽  
Michael PH Stumpf
Keyword(s):  
Stem Cells ◽  
Population Dynamics ◽  
Stem Cell ◽  
Cell Fate ◽  
Stem Cell Niche ◽  
Alternative Possibilities ◽  
Extrinsic Factors ◽  
Cell Fate Decisions ◽  
Wide Range ◽  
Cell Niche

Within populations of cells, fate decisions are controlled by an indeterminate combination of cell-intrinsic and cell-extrinsic factors. In the case of stem cells, the stem cell niche is believed to maintain "stemness" through communication and interactions between the stem cells and one or more other cell-types that contribute to the niche conditions. To investigate the robustness of cell fate decisions in the stem cell hierarchy and the role that the niche plays, we introduce simple mathematical models of stem and progenitor cells, their progeny and their interplay in the niche. These models capture the fundamental processes of proliferation and differentiation and allow us to consider alternative possibilities regarding how niche-mediated signalling feedback regulates the niche dynamics. Generalised stability analysis of these stem cell niche systems enables us to describe the stability properties of each model. We find that although the number of feasible states depends on the model, their probabilities of stability in general do not: stem cell--niche models are stable across a wide range of parameters. We demonstrate that niche-mediated feedback increases the number of stable steady states, and show how distinct cell states have distinct branching characteristics. The ecological feedback and interactions mediated by the stem cell niche thus lend (surprisingly) high levels of robustness to the stem and progenitor cell population dynamics. Furthermore, cell--cell interactions are sufficient for populations of stem cells and their progeny to achieve stability and maintain homeostasis. We show that the robustness of the niche -- and hence of the stem cell pool in the niche -- depends only weakly, if at all, on the complexity of the niche make-up: simple as well as complicated niche systems are capable of supporting robust and stable stem cell dynamics.

scholarly journals Biomaterial Approaches for Stem Cell-Based Myocardial Tissue Engineering

2015 ◽  
Vol 10s1 ◽  
pp. BMI.S20313 ◽  
Author(s):  
Josh Cutts ◽  
Mehdi Nikkhah ◽  
David A. Brafman
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Raw Materials ◽  
Cell Types ◽  
Heart Tissue ◽  
Cardiac Damage ◽  
Low Efficiency

Adult and pluripotent stem cells represent a ready supply of cellular raw materials that can be used to generate the functionally mature cells needed to replace damaged or diseased heart tissue. However, the use of stem cells for cardiac regenerative therapies is limited by the low efficiency by which stem cells are differentiated in vitro to cardiac lineages as well as the inability to effectively deliver stem cells and their derivatives to regions of damaged myocardium. In this review, we discuss the various biomaterial-based approaches that are being implemented to direct stem cell fate both in vitro and in vivo. First, we discuss the stem cell types available for cardiac repair and the engineering of naturally and synthetically derived biomaterials to direct their in vitro differentiation to the cell types that comprise heart tissue. Next, we describe biomaterial-based approaches that are being implemented to enhance the in vivo integration and differentiation of stem cells delivered to areas of cardiac damage. Finally, we present emerging trends of using stem cell-based biomaterial approaches to deliver pro-survival factors and fully vascularized tissue to the damaged and diseased cardiac tissue.

Stem Cell Cure for Kidney Injury: Therapy to Solve Most Complex Issues in Renal System

2020 ◽  
Author(s):  
Prithiv K R Kumar
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Kidney Injury ◽  
Cell Types ◽  
Tissue Remodelling ◽  
Major Health Problem ◽  
In Vivo Experiments ◽  
Renal Regeneration ◽  
Induced Pluripotent

Renal failure is a major health problem. The mortality rate remain high despite of several therapies. The most complex of the renal issues are solved through stem cells. In this review, different mechanism for cure of chronic kidney injury along with cell engraftment incorporated into renal structures will be analysed. Paracrine activities of embryonic or induced Pluripotent stem cells are explored on the basis of stem cell-induced kidney regeneration. Several experiments have been conducted to advance stem cells to ensure the restoration of renal functions. More vigour and organised protocols for delivering stem cells is a possibility for advancement in treatment of renal disease. Also there is a need for pressing therapies to replicate the tissue remodelling and cellular repair processes suitable for renal organs. Stem cells are the undifferentiated cells that have the ability to multiply into several cell types. In vivo experiments on animal’s stem cells have shown significant improvements in the renal regeneration and functions of organs. Nevertheless more studies show several improvements in the kidney repair due to stem cell regeneration.

scholarly journals Induced Pluripotent Stem Cells (iPSCs) in Vascular Research: from Two- to Three-Dimensional Organoids

2021 ◽  
Author(s):  
Anja Trillhaase ◽  
Marlon Maertens ◽  
Zouhair Aherrahrou ◽  
Jeanette Erdmann
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Stem Cell Research ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
3D Models ◽  
Induced Pluripotent

AbstractStem cell technology has been around for almost 30 years and in that time has grown into an enormous field. The stem cell technique progressed from the first successful isolation of mammalian embryonic stem cells (ESCs) in the 1990s, to the production of human induced-pluripotent stem cells (iPSCs) in the early 2000s, to finally culminate in the differentiation of pluripotent cells into highly specialized cell types, such as neurons, endothelial cells (ECs), cardiomyocytes, fibroblasts, and lung and intestinal cells, in the last decades. In recent times, we have attained a new height in stem cell research whereby we can produce 3D organoids derived from stem cells that more accurately mimic the in vivo environment. This review summarizes the development of stem cell research in the context of vascular research ranging from differentiation techniques of ECs and smooth muscle cells (SMCs) to the generation of vascularized 3D organoids. Furthermore, the different techniques are critically reviewed, and future applications of current 3D models are reported. Graphical abstract

scholarly journals Histone Acetyltransferases and Stem Cell Identity

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2407
Author(s):  
Ruicen He ◽  
Arthur Dantas ◽  
Karl Riabowol
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Epigenetic Modification ◽  
Cell Types ◽  
Histone Acetyltransferases ◽  
Specific Cell ◽  
Cell Fates ◽  
Cell Identity ◽  
Hematopoietic Stem

Acetylation of histones is a key epigenetic modification involved in transcriptional regulation. The addition of acetyl groups to histone tails generally reduces histone-DNA interactions in the nucleosome leading to increased accessibility for transcription factors and core transcriptional machinery to bind their target sequences. There are approximately 30 histone acetyltransferases and their corresponding complexes, each of which affect the expression of a subset of genes. Because cell identity is determined by gene expression profile, it is unsurprising that the HATs responsible for inducing expression of these genes play a crucial role in determining cell fate. Here, we explore the role of HATs in the maintenance and differentiation of various stem cell types. Several HAT complexes have been characterized to play an important role in activating genes that allow stem cells to self-renew. Knockdown or loss of their activity leads to reduced expression and or differentiation while particular HATs drive differentiation towards specific cell fates. In this study we review functions of the HAT complexes active in pluripotent stem cells, hematopoietic stem cells, muscle satellite cells, mesenchymal stem cells, neural stem cells, and cancer 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 daf-16/FOXO blocks adult cell fate in Caenorhabditis elegans dauer larvae via lin-41/TRIM71

PLoS Genetics ◽  
2021 ◽  
Vol 17 (11) ◽  
pp. e1009881
Author(s):  
Matthew J. Wirick ◽  
Allison R. Cale ◽  
Isaac T. Smith ◽  
Amelia F. Alessi ◽  
Margaret R. Starostik ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Rna Binding ◽  
Cell Model ◽  
Cell Types ◽  
Adult Cell ◽  
Heterochronic Gene ◽  
Foxo Transcription Factors ◽  
Dauer Larvae

Many tissue-specific stem cells maintain the ability to produce multiple cell types during long periods of non-division, or quiescence. FOXO transcription factors promote quiescence and stem cell maintenance, but the mechanisms by which FOXO proteins promote multipotency during quiescence are still emerging. The single FOXO ortholog in C. elegans, daf-16, promotes entry into a quiescent and stress-resistant larval stage called dauer in response to adverse environmental cues. During dauer, stem and progenitor cells maintain or re-establish multipotency to allow normal development to resume after dauer. We find that during dauer, daf-16/FOXO prevents epidermal stem cells (seam cells) from prematurely adopting differentiated, adult characteristics. In particular, dauer larvae that lack daf-16 misexpress collagens that are normally adult-enriched. Using col-19p::gfp as an adult cell fate marker, we find that all major daf-16 isoforms contribute to opposing col-19p::gfp expression during dauer. By contrast, daf-16(0) larvae that undergo non-dauer development do not misexpress col-19p::gfp. Adult cell fate and the timing of col-19p::gfp expression are regulated by the heterochronic gene network, including lin-41 and lin-29. lin-41 encodes an RNA-binding protein orthologous to LIN41/TRIM71 in mammals, and lin-29 encodes a conserved zinc finger transcription factor. In non-dauer development, lin-41 opposes adult cell fate by inhibiting the translation of lin-29, which directly activates col-19 transcription and promotes adult cell fate. We find that during dauer, lin-41 blocks col-19p::gfp expression, but surprisingly, lin-29 is not required in this context. Additionally, daf-16 promotes the expression of lin-41 in dauer larvae. The col-19p::gfp misexpression phenotype observed in dauer larvae with reduced daf-16 requires the downregulation of lin-41, but does not require lin-29. Taken together, this work demonstrates a novel role for daf-16/FOXO as a heterochronic gene that promotes expression of lin-41/TRIM71 to contribute to multipotent cell fate in a quiescent stem cell model.

daf-16/FOXO blocks adult cell fate in Caenorhabditis elegans dauer larvae via lin-41/TRIM71

2021 ◽  
Author(s):  
Matthew J Wirick ◽  
Allison R Cale ◽  
Isaac T Smith ◽  
Amelia F Alessi ◽  
Margaret R Starostik ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Rna Binding ◽  
Cell Model ◽  
Cell Types ◽  
Adult Cell ◽  
Heterochronic Gene ◽  
Foxo Transcription Factors ◽  
Dauer Larvae

Many tissue-specific stem cells maintain the ability to produce multiple cell types during long periods of non-division, or quiescence. FOXO transcription factors promote quiescence and stem cell maintenance, but the mechanisms by which FOXO proteins promote multipotency during quiescence are still emerging. The single FOXO ortholog in C. elegans, daf-16, promotes entry into a quiescent and stress-resistant larval stage called dauer in response to adverse environmental cues. During dauer, stem and progenitor cells maintain or re-establish multipotency to allow normal development to resume after dauer. We find that during dauer, daf-16/FOXO prevents epidermal stem cells (seam cells) from prematurely adopting differentiated, adult characteristics. In particular, dauer larvae that lack daf-16 misexpress collagens that are normally adult-enriched. Using col-19p::gfp as an adult cell fate marker, we find that all major daf-16 isoforms contribute to opposing col-19p::gfp expression during dauer. By contrast, daf-16(0) larvae that undergo non-dauer development do not misexpress col-19p::gfp. Adult cell fate and the timing of col-19p::gfp expression are regulated by the heterochronic gene network, including lin-41 and lin-29. lin-41 encodes an RNA-binding protein orthologous to LIN41/TRIM71 in mammals, and lin-29 encodes a conserved zinc finger transcription factor. In non-dauer development lin-41 opposes adult cell fate by inhibiting the translation of lin-29, which directly activates col-19 transcription and promotes adult cell fate. We find that during dauer, lin-41 blocks col-19p::gfp expression, but surprisingly, lin-29 is not required in this context. Additionally, daf-16 promotes the expression of lin-41 in dauer larvae. The col-19p::gfp misexpression phenotype observed in dauer larvae with reduced daf-16 requires the downregulation of lin-41, but does not require lin-29. Taken together, this work demonstrates a novel role for daf-16/FOXO as a heterochronic gene that promotes expression of lin-41/TRIM71 to contribute to multipotent cell fate in a quiescent stem cell model.

scholarly journals Do Neural Stem Cells Have a Choice? Heterogenic Outcome of Cell Fate Acquisition in Different Injury Models

2019 ◽  
Vol 20 (2) ◽  
pp. 455 ◽  
Author(s):  
Felix Beyer ◽  
Iria Samper Agrelo ◽  
Patrick Küry
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Ex Vivo ◽  
Meta Analysis ◽  
Cell Types ◽  
Adult Brain ◽  
Repair Capacity ◽  
Cell Fate Decisions ◽  
Limiting Parameters

The adult mammalian central nervous system (CNS) is generally considered as repair restricted organ with limited capacities to regenerate lost cells and to successfully integrate them into damaged nerve tracts. Despite the presence of endogenous immature cell types that can be activated upon injury or in disease cell replacement generally remains insufficient, undirected, or lost cell types are not properly generated. This limitation also accounts for the myelin repair capacity that still constitutes the default regenerative activity at least in inflammatory demyelinating conditions. Ever since the discovery of endogenous neural stem cells (NSCs) residing within specific niches of the adult brain, as well as the description of procedures to either isolate and propagate or artificially induce NSCs from various origins ex vivo, the field has been rejuvenated. Various sources of NSCs have been investigated and applied in current neuropathological paradigms aiming at the replacement of lost cells and the restoration of functionality based on successful integration. Whereas directing and supporting stem cells residing in brain niches constitutes one possible approach many investigations addressed their potential upon transplantation. Given the heterogeneity of these studies related to the nature of grafted cells, the local CNS environment, and applied implantation procedures we here set out to review and compare their applied protocols in order to evaluate rate-limiting parameters. Based on our compilation, we conclude that in healthy CNS tissue region specific cues dominate cell fate decisions. However, although increasing evidence points to the capacity of transplanted NSCs to reflect the regenerative need of an injury environment, a still heterogenic picture emerges when analyzing transplantation outcomes in injury or disease models. These are likely due to methodological differences despite preserved injury environments. Based on this meta-analysis, we suggest future NSC transplantation experiments to be conducted in a more comparable way to previous studies and that subsequent analyses must emphasize regional heterogeneity such as accounting for differences in gray versus white matter.

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