scholarly journals Biomaterial Engineering for Controlling Pluripotent Stem Cell Fate

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Taylor B. Bertucci ◽  
Guohao Dai
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Cell Fates ◽  
Self Renewal ◽  
Environmental Signals ◽  
Stem Cell Fate ◽  
Cell Source ◽  
3D Environments ◽  
Stem Cell Niches

Pluripotent stem cells (PSCs) represent an exciting cell source for tissue engineering and regenerative medicine due to their self-renewal and differentiation capacities. The majority of current PSC protocols rely on 2D cultures and soluble factors to guide differentiation; however, many other environmental signals are beginning to be explored using biomaterial platforms. Biomaterials offer new opportunities to engineer the stem cell niches and 3D environments for exploring biophysical and immobilized signaling cues to further our control over stem cell fate. Here, we review the biomaterial platforms that have been engineered to control PSC fate. We explore how altering immobilized biochemical cues and biophysical cues such as dimensionality, stiffness, and topography can enhance our control over stem cell fates. Finally, we highlight biomaterial culture systems that assist in the translation of PSC technologies for clinical applications.

scholarly journals Epidermal stem cells self-renew upon neighboring differentiation

2017 ◽  
Author(s):  
Kailin R. Mesa ◽  
Kyogo Kawaguchi ◽  
David G. Gonzalez ◽  
Katie Cockburn ◽  
Jonathan Boucher ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Nearest Neighbor ◽  
Population Level ◽  
Cell Fates ◽  
Self Renewal ◽  
Stem Cell Fate ◽  
Asymmetric Divisions ◽  
Functional Blocking

Many adult tissues are dynamically sustained by the rapid turnover of stem cells. Yet, how cell fates such as self-renewal and differentiation are orchestrated to achieve long-term homeostasis remains elusive. Studies utilizing clonal tracing experiments in multiple tissues have argued that while stem cell fate is balanced at the population level, individual cell fate - to divide or differentiate – is determined intrinsically by each cell seemingly at random ( 1 2 3 4 5). These studies leave open the question of how cell fates are regulated to achieve fate balance across the tissue. Stem cell fate choices could be made autonomously by each cell throughout the tissue or be the result of cell coordination ( 6 7). Here we developed a novel live tracking strategy that allowed recording of every division and differentiation event within a region of epidermis for a week. These measurements reveal that stem cell fates are not autonomous. Rather, direct neighbors undergo coupled opposite fate decisions. We further found a clear ordering of events, with self-renewal triggered by neighbor differentiation, but not vice-versa. Typically, around 1-2 days after cell delamination, a neighboring cell entered S/G2 phase and divided. Functional blocking of this local feedback showed that differentiation continues to occur in the absence of cell division, resulting in a rapid depletion of the epidermal stem cell pool. We thus demonstrate that the epidermis is maintained by nearest neighbor coordination of cell fates, rather than by asymmetric divisions or fine-tuned cell-autonomous stochastic fate choices. These findings establish differentiation-dependent division as a core feature of homeostatic control, and define the relevant time and length scales over which homeostasis is enforced in epithelial tissues.

Asymmetric organelle inheritance predicts human blood stem cell fate

Blood ◽  
2021 ◽  
Author(s):  
Dirk Loeffler ◽  
Florin Schneiter ◽  
Weijia Wang ◽  
Arne Wehling ◽  
Tobias Kull ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Cell Fate ◽  
Human Blood ◽  
Asymmetric Cell Division ◽  
Cell Fates ◽  
Hematopoietic Stem ◽  
Stem Cell Fate ◽  
Blood Stem Cells

Understanding human hematopoietic stem cell fate control is important for their improved therapeutic manipulation. Asymmetric cell division, the asymmetric inheritance of factors during division instructing future daughter cell fates, was recently described in mouse blood stem cells. In human blood stem cells, the possible existence of asymmetric cell division remained unclear due to technical challenges in its direct observation. Here, we use long-term quantitative single-cell imaging to show that lysosomes and active mitochondria are asymmetrically inherited in human blood stem cells and that their inheritance is a coordinated, non-random process. Furthermore, multiple additional organelles, including autophagosomes, mitophagosomes, autolysosomes and recycling endosomes show preferential asymmetric co-segregation with lysosomes. Importantly, asymmetric lysosomal inheritance predicts future asymmetric daughter cell cycle length, differentiation and stem cell marker expression, while asymmetric inheritance of active mitochondria correlates with daughter metabolic activity. Hence, human hematopoietic stem cell fates are regulated by asymmetric cell division, with both mechanistic evolutionary conservation and differences to the mouse system.

scholarly journals The Role of SMAD4 in Human Embryonic Stem Cell Self-Renewal and Stem Cell Fate

Stem Cells ◽  
2010 ◽  
pp. N/A-N/A ◽  
Author(s):  
Stuart Avery ◽  
Gaetano Zafarana ◽  
Paul J. Gokhale ◽  
Peter W. Andrews
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Cell Fate ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Self Renewal ◽  
Stem Cell Fate

scholarly journals Brain micro-ecologies: neural stem cell niches in the adult mammalian brain

2007 ◽  
Vol 363 (1489) ◽  
pp. 123-137 ◽  
Author(s):  
Patricio A Riquelme ◽  
Elodie Drapeau ◽  
Fiona Doetsch
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Neural Stem Cell ◽  
Subventricular Zone ◽  
Hippocampal Formation ◽  
Mammalian Brain ◽  
Adult Neural Stem Cell ◽  
Stem Cell Fate ◽  
Stem Cell Niches ◽  
Adult Mammalian Brain

Neurogenesis persists in two germinal regions in the adult mammalian brain, the subventricular zone of the lateral ventricles and the subgranular zone in the hippocampal formation. Within these two neurogenic niches, specialized astrocytes are neural stem cells, capable of self-renewing and generating neurons and glia. Cues within the niche, from cell–cell interactions to diffusible factors, are spatially and temporally coordinated to regulate proliferation and neurogenesis, ultimately affecting stem cell fate choices. Here, we review the components of adult neural stem cell niches and how they act to regulate neurogenesis in these regions.

scholarly journals Deubiquitinating Enzyme-Mediated Signaling Networks in Cancer Stem Cells

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3253
Author(s):  
Kamini Kaushal ◽  
Suresh Ramakrishna
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Cell Fate ◽  
Deubiquitinating Enzymes ◽  
Self Renewal ◽  
Stem Cell Fate ◽  
Multiple Tumor ◽  
Cell Fate Decisions

Cancer stem cells (CSCs) have both the capacity for self-renewal and the potential to differentiate and contribute to multiple tumor properties, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. Thus, CSCs are considered to be promising therapeutic targets for cancer therapy. The function of CSCs can be regulated by ubiquitination and deubiquitination of proteins related to the specific stemness of the cells executing various stem cell fate choices. To regulate the balance between ubiquitination and deubiquitination processes, the disassembly of ubiquitin chains from specific substrates by deubiquitinating enzymes (DUBs) is crucial. Several key developmental and signaling pathways have been shown to play essential roles in this regulation. Growing evidence suggests that overactive or abnormal signaling within and among these pathways may contribute to the survival of CSCs. These signaling pathways have been experimentally shown to mediate various stem cell properties, such as self-renewal, cell fate decisions, survival, proliferation, and differentiation. In this review, we focus on the DUBs involved in CSCs signaling pathways, which are vital in regulating their stem-cell fate determination.

scholarly journals Asymmetric histone inheritance regulates stem cell fate in Drosophila midgut

2020 ◽  
Author(s):  
Emily Zion ◽  
Xin Chen
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Biological Significance ◽  
Cell Lineage ◽  
Germline Stem Cells ◽  
Cell Fates ◽  
Stem Cell Fate ◽  
Distinct Cell

AbstractA fundamental question in developmental biology is how distinct cell fates are established and maintained through epigenetic mechanisms in multicellular organisms. Here, we report that preexisting (old) and newly synthesized (new) histones H3 and H4 are asymmetrically inherited by the distinct daughter cells during asymmetric division of Drosophila intestinal stem cells (ISCs). By contrast, in symmetrically dividing ISCs that produce two self-renewed stem cells, old and new H3 and H4 show symmetric inheritance patterns. These results indicate that asymmetric histone inheritance is tightly associated with the distinct daughter cell fates. To further understand the biological significance of this asymmetry, we express a mutant histone that compromises asymmetric histone inheritance pattern. We find increased symmetric ISC division and ISC tumors during aging under this condition. Together, our results demonstrate that asymmetric histone inheritance is important for establishing distinct cell identities in a somatic stem cell lineage, consistent with previous findings in asymmetrically dividing male germline stem cells in Drosophila. Therefore, this work sheds light on the principles of histone inheritance in regulating stem cell fate in vivo.

scholarly journals Stem cell fate determination through protein O-GlcNAcylation.

2020 ◽  
pp. jbc.REV120.014915
Author(s):  
Muhammad Abid Sheikh ◽  
Bright Starling Emerald ◽  
Suraiya Anjum Ansari
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Metabolic Pathways ◽  
Regulatory Mechanisms ◽  
Self Renewal ◽  
Stem Cell Fate ◽  
Specific Differentiation ◽  
Gene Regulatory

Embryonic and adult stem cells possess the capability of self-renewal and lineage specific differentiation. The intricate balance between self-renewal and differentiation is governed by developmental signals and cell type specific gene regulatory mechanisms. A perturbed intra/extracellular environment during lineage specification could affect stem cell fate decisions resulting in pathology. Growing evidence demonstrates that metabolic pathways govern epigenetic regulation of gene expression during stem cell fate commitment through the utilization of metabolic intermediates or end products of metabolic pathways as substrates for enzymatic histone/DNA modifications. UDP-GlcNAc is one such metabolite which acts as a substrate for enzymatic mono-glycosylation of various nuclear, cytosolic, and mitochondrial proteins on serine/threonine amino acid residues, a process termed protein O-GlcNAcylation. The levels of GlcNAc inside the cells depend on the nutrient availability, especially glucose. Thus, this metabolic sensor could modulate gene expression through O-GlcNAc modification of histones or other proteins in response to metabolic fluctuations. Herein, we review evidence demonstrating how stem cells couple metabolic inputs to gene regulatory pathways through O-GlcNAc-mediated epigenetic/transcriptional regulatory mechanisms to govern self-renewal and lineage specific differentiation programs. This review will serve as a primer for researchers seeking to better understand how O-GlcNAc influences stemness, and may catalyze the discovery of new stem cell-based therapeutic approaches.

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