Intestine-enriched apolipoprotein b orthologs regulate stem cell differentiation and regeneration in planarians

Little is known about how lipid mobilization and utilization are modulated during stem-cell-driven tissue growth during regeneration. Planarian flatworms can regenerate all missing tissues in 10 days due to the proliferation and differentiation of pluripotent somatic stem cells called neoblasts. In planarians, diet-derived neutral lipids are stored in the intestine. Here, we identify two intestine-enriched paralogs of apolipoprotein b, apob-1 and apob-2, that are required for regeneration. Consistent with apolipoproteins' known roles regulating neutral lipid (NL) transport in lipoprotein particles (LPs), NLs increased in the intestine upon simultaneous dsRNA-mediated knockdown of apob-1 and apob-2, but were depleted in neoblasts and their progeny. apob knockdown reduced regeneration blastema morphogenesis, and delayed re-establishment of axial polarity and regeneration of multiple organs. Using flow cytometry, we found that neoblast progeny accumulated in apob(RNAi) animals, with minimal effects on neoblast maintenance or proliferation. In addition, ApoB reduction primarily dysregulated expression of transcripts enriched in neoblast progeny and mature cell types, compared to cycling neoblasts. Together, our results provide evidence that intestine-derived lipids serve as a source of metabolites required for neoblast differentiation. In addition, these findings demonstrate that planarians are a tractable model for elucidating specialized mechanisms by which lipid metabolism must be regulated during animal regeneration.

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Comparison of the Proliferation and Differentiation Potential of Human Urine-, Placenta Decidua Basalis-, and Bone Marrow-Derived Stem Cells

Stem Cells International ◽

10.1155/2018/7131532 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Chengguang Wu ◽

Long Chen ◽

Yi-zhou Huang ◽

Yongcan Huang ◽

Ornella Parolini ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Stem Cell Differentiation ◽

Cell Types ◽

Stem Cell Marker ◽

Differentiation Potential ◽

Multipotent Stem Cells ◽

Decidua Basalis

Human multipotent stem cell-based therapies have shown remarkable potential in regenerative medicine and tissue engineering applications due to their abilities of self-renewal and differentiation into multiple adult cell types under appropriate conditions. Presently, human multipotent stem cells can be isolated from different sources, but variation among their basic biology can result in suboptimal selection of seed cells in preclinical and clinical research. Thus, the goal of this study was to compare the biological characteristics of multipotent stem cells isolated from human bone marrow, placental decidua basalis, and urine, respectively. First, we found that urine-derived stem cells (USCs) displayed different morphologies compared with other stem cell types. USCs and placenta decidua basalis-derived mesenchymal stem cells (PDB-MSCs) had superior proliferation ability in contrast to bone marrow-derived mesenchymal stem cells (BMSCs); these cells grew to have the highest colony-forming unit (CFU) counts. In phenotypic analysis using flow cytometry, similarity among all stem cell marker expression was found, excluding CD29 and CD105. Regarding stem cell differentiation capability, USCs were observed to have better adipogenic and endothelial abilities as well as vascularization potential compared to BMSCs and PDB-MSCs. As for osteogenic and chondrogenic induction, BMSCs were superior to all three stem cell types. Future therapeutic indications and clinical applications of BMSCs, PDB-MSCs, and USCs should be based on their characteristics, such as growth kinetics and differentiation capabilities.

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Regulatory network characterization in development: challenges and opportunities

F1000Research ◽

10.12688/f1000research.15271.1 ◽

2018 ◽

Vol 7 ◽

pp. 1477

Author(s):

Guangdun Peng ◽

Jing-Dong J. Han

Keyword(s):

Stem Cell ◽

Cell Fate ◽

Regulatory Networks ◽

Stem Cell Differentiation ◽

Cell Types ◽

Mammalian Development ◽

Distinct Cell ◽

Challenges And Opportunities ◽

Cell Processes ◽

Early Mammalian Development

Embryonic development and stem cell differentiation, during which coordinated cell fate specification takes place in a spatial and temporal context, serve as a paradigm for studying the orderly assembly of gene regulatory networks (GRNs) and the fundamental mechanism of GRNs in driving lineage determination. However, knowledge of reliable GRN annotation for dynamic development regulation, particularly for unveiling the complex temporal and spatial architecture of tissue stem cells, remains inadequate. With the advent of single-cell RNA sequencing technology, elucidating GRNs in development and stem cell processes poses both new challenges and unprecedented opportunities. This review takes a snapshot of some of this work and its implication in the regulative nature of early mammalian development and specification of the distinct cell types during embryogenesis.

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PDMS Nano-Modified Scaffolds for Improvement of Stem Cells Proliferation and Differentiation in Microfluidic Platform

Nanomaterials ◽

10.3390/nano10040668 ◽

2020 ◽

Vol 10 (4) ◽

pp. 668 ◽

Cited By ~ 4

Author(s):

Hadi Hashemzadeh ◽

Abdollah Allahverdi ◽

Mosslim Sedghi ◽

Zahra Vaezi ◽

Tahereh Tohidi Moghadam ◽

...

Keyword(s):

Stem Cells ◽

Surface Roughness ◽

Stem Cell ◽

Cell Surface ◽

Superparamagnetic Iron Oxide ◽

Fold Increase ◽

Stem Cell Differentiation ◽

Gold Nanowires ◽

Cell Substrate ◽

Proliferation And Differentiation

Microfluidics cell-based assays require strong cell-substrate adhesion for cell viability, proliferation, and differentiation. The intrinsic properties of PDMS, a commonly used polymer in microfluidics systems, regarding cell-substrate interactions have limited its application for microfluidics cell-based assays. Various attempts by previous researchers, such as chemical modification, plasma-treatment, and protein-coating of PDMS revealed some improvements. These strategies are often reversible, time-consuming, short-lived with either cell aggregates formation, not cost-effective as well as not user- and eco-friendly too. To address these challenges, cell-surface interaction has been tuned by the modification of PDMS doped with different biocompatible nanomaterials. Gold nanowires (AuNWs), superparamagnetic iron oxide nanoparticles (SPIONs), graphene oxide sheets (GO), and graphene quantum dot (GQD) have already been coupled to PDMS as an alternative biomaterial enabling easy and straightforward integration during microfluidic fabrication. The synthesized nanoparticles were characterized by corresponding methods. Physical cues of the nanostructured substrates such as Young’s modulus, surface roughness, and nanotopology have been carried out using atomic force microscopy (AFM). Initial biocompatibility assessment of the nanocomposites using human amniotic mesenchymal stem cells (hAMSCs) showed comparable cell viabilities among all nanostructured PDMS composites. Finally, osteogenic stem cell differentiation demonstrated an improved differentiation rate inside microfluidic devices. The results revealed that the presence of nanomaterials affected a 5- to 10-fold increase in surface roughness. In addition, the results showed enhancement of cell proliferation from 30% (pristine PDMS) to 85% (nano-modified scaffolds containing AuNWs and SPIONs), calcification from 60% (pristine PDMS) to 95% (PDMS/AuNWs), and cell surface marker expression from 40% in PDMS to 77% in SPION- and AuNWs-PDMS scaffolds at 14 day. Our results suggest that nanostructured composites have a very high potential for stem cell studies and future therapies.

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HDAC3 is crucial in shear- and VEGF-induced stem cell differentiation toward endothelial cells

The Journal of Cell Biology ◽

10.1083/jcb.200605113 ◽

2006 ◽

Vol 174 (7) ◽

pp. 1059-1069 ◽

Cited By ~ 175

Author(s):

Lingfang Zeng ◽

Qingzhong Xiao ◽

Andriana Margariti ◽

Zhongyi Zhang ◽

Anna Zampetaki ◽

...

Keyword(s):

Endothelial Cells ◽

Shear Stress ◽

Stem Cell ◽

Cell Differentiation ◽

Laminar Flow ◽

Progenitor Cell ◽

Stem Cell Differentiation ◽

Es Cell ◽

Local Flow ◽

Proliferation And Differentiation

Reendothelialization involves endothelial progenitor cell (EPC) homing, proliferation, and differentiation, which may be influenced by fluid shear stress and local flow pattern. This study aims to elucidate the role of laminar flow on embryonic stem (ES) cell differentiation and the underlying mechanism. We demonstrated that laminar flow enhanced ES cell–derived progenitor cell proliferation and differentiation into endothelial cells (ECs). Laminar flow stabilized and activated histone deacetylase 3 (HDAC3) through the Flk-1–PI3K–Akt pathway, which in turn deacetylated p53, leading to p21 activation. A similar signal pathway was detected in vascular endothelial growth factor–induced EC differentiation. HDAC3 and p21 were detected in blood vessels during embryogenesis. Local transfer of ES cell–derived EPC incorporated into injured femoral artery and reduced neointima formation in a mouse model. These data suggest that shear stress is a key regulator for stem cell differentiation into EC, especially in EPC differentiation, which can be used for vascular repair, and that the Flk-1–PI3K–Akt–HDAC3–p53–p21 pathway is crucial in such a process.

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Effect of Sulfur on Nitrogen-Containing Plasma Polymers in Promoting Osteogenic Differentiation of Wharton’s Jelly Mesenchymal Stem Cells

Sains Malaysiana ◽

10.17576/jsm-2021-5001-23 ◽

2021 ◽

Vol 50 (1) ◽

pp. 239-251

Author(s):

Kim Shyong Siow ◽

Arifah Rahman ◽

Amnani Aminuddin ◽

Pei Yuen Ng

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Osteogenic Differentiation ◽

Stem Cell Differentiation ◽

Wharton’S Jelly ◽

Oxidation States ◽

Plasma Polymers ◽

Wharton's Jelly ◽

Proliferation And Differentiation

The role of sulfur and its synergistic effects with nitrogen moieties in mediating stem cell proliferation and differentiation has become of interest to the tissue engineering community due to chemical similarities with the glycosaminoglycans found in human tissues and cells. Glycosaminoglycans are biomolecules known to influence stem cell differentiation, but the roles of sulfur with different oxidation states on nitrogen-containing polymers have not been fully understood nor investigated. In this study, we used the plasma polymerization of 1,7-octadiene (ppOD), n-heptylamine (ppHA), ppHA grafted with vinyl-sulfonate via Michael-type addition (ppHA-SO3), thiophene (ppT), and ppT with air plasma treatment (ppT-air) to produce controlled amounts of nitrogen and sulfur moieties having different oxidation states, as confirmed by x-ray photoelectron spectroscopy. Assays of the proliferation and osteogenic activities of Wharton’s jelly mesenchymal stem cells (WJ-MSCs) showed the highest activities for ppHA, followed by ppHA-SO3, due to high percentages of amines/amides and the absence of SO3 moieties in ppHA. Other plasma polymers showed less proliferation and osteogenic differentiation than the positive control (glass substrate); however, WJ-MSCs grown on ppT-air with its high percentages of SO4 displayed cytoskeletons intensified with actin stress fiber, unlike the thiol-dominated ppT. Finally, the presence of methyl groups in ppOD severely limited WJ-MSCs proliferation and differentiation. Overall, these results confirm the beneficial effects of amine/amide groups on WJ-MSCs proliferation and osteogenic differentiation, but the combination of these groups with sulfur of various oxidation states failed to further enhance such cellular activities.

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Oncogenes, Proto-Oncogenes, and Lineage Restriction of Cancer Stem Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22189667 ◽

2021 ◽

Vol 22 (18) ◽

pp. 9667

Author(s):

Geoffrey Brown

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Fate ◽

Cell Lineage ◽

Cell Types ◽

Mature Cell ◽

Cellular Gene ◽

Hematopoietic Stem ◽

Homeostatic Process ◽

Epigenetic Events

In principle, an oncogene is a cellular gene (proto-oncogene) that is dysfunctional, due to mutation and fusion with another gene or overexpression. Generally, oncogenes are viewed as deregulating cell proliferation or suppressing apoptosis in driving cancer. The cancer stem cell theory states that most, if not all, cancers are a hierarchy of cells that arises from a transformed tissue-specific stem cell. These normal counterparts generate various cell types of a tissue, which adds a new dimension to how oncogenes might lead to the anarchic behavior of cancer cells. It is that stem cells, such as hematopoietic stem cells, replenish mature cell types to meet the demands of an organism. Some oncogenes appear to deregulate this homeostatic process by restricting leukemia stem cells to a single cell lineage. This review examines whether cancer is a legacy of stem cells that lose their inherent versatility, the extent that proto-oncogenes play a role in cell lineage determination, and the role that epigenetic events play in regulating cell fate and tumorigenesis.

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Application of Nanotechnology in Stem-Cell-Based Therapy of Neurodegenerative Diseases

Applied Sciences ◽

10.3390/app10144852 ◽

2020 ◽

Vol 10 (14) ◽

pp. 4852 ◽

Cited By ~ 1

Author(s):

Shima Masoudi Asil ◽

Jyoti Ahlawat ◽

Gileydis Guillama Barroso ◽

Mahesh Narayan

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Therapy ◽

Stem Cell Therapy ◽

Large Scale ◽

Stem Cell Differentiation ◽

Cell Types ◽

Clinical Scales ◽

Adverse Health Outcomes ◽

Cell Based Therapy

In addition to adverse health outcomes, neurological disorders have serious societal and economic impacts on patients, their family and society as a whole. There is no definite treatment for these disorders, and current available drugs only slow down the progression of the disease. In recent years, application of stem cells has been widely advanced due to their potential of self-renewal and differentiation to different cell types which make them suitable candidates for cell therapy. In particular, this approach offers great opportunities for the treatment of neurodegenerative disorders. However, some major issues related to stem-cell therapy, including their tumorigenicity, viability, safety, metastases, uncontrolled differentiation and possible immune response have limited their application in clinical scales. To address these challenges, a combination of stem-cell therapy with nanotechnology can be a solution. Nanotechnology has the potential of improvement of stem-cell therapy by providing ideal substrates for large scale proliferation of stem cells. Application of nanomaterial in stem-cell culture will be also beneficial to modulation of stem-cell differentiation using nanomedicines. Nanodelivery of functional compounds can enhance the efficiency of neuron therapy by stem cells and development of nanobased techniques for real-time, accurate and long-lasting imaging of stem-cell cycle processes. However, these novel techniques need to be investigated to optimize their efficiency in treatment of neurologic diseases.

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CATaDa reveals global remodelling of chromatin accessibility during stem cell differentiation in vivo

eLife ◽

10.7554/elife.32341 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 29

Author(s):

Gabriel N Aughey ◽

Alicia Estacio Gomez ◽

Jamie Thomson ◽

Hang Yin ◽

Tony D Southall

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Differentiation ◽

Ectopic Expression ◽

Stem Cell Differentiation ◽

Cell Types ◽

Regulatory Elements ◽

Chromatin Accessibility ◽

Global Changes

During development eukaryotic gene expression is coordinated by dynamic changes in chromatin structure. Measurements of accessible chromatin are used extensively to identify genomic regulatory elements. Whilst chromatin landscapes of pluripotent stem cells are well characterised, chromatin accessibility changes in the development of somatic lineages are not well defined. Here we show that cell-specific chromatin accessibility data can be produced via ectopic expression of E. coli Dam methylase in vivo, without the requirement for cell-sorting (CATaDa). We have profiled chromatin accessibility in individual cell-types of Drosophila neural and midgut lineages. Functional cell-type-specific enhancers were identified, as well as novel motifs enriched at different stages of development. Finally, we show global changes in the accessibility of chromatin between stem-cells and their differentiated progeny. Our results demonstrate the dynamic nature of chromatin accessibility in somatic tissues during stem cell differentiation and provide a novel approach to understanding gene regulatory mechanisms underlying development.

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Glycosaminoglycans as regulators of stem cell differentiation

Biochemical Society Transactions ◽

10.1042/bst0390383 ◽

2011 ◽

Vol 39 (1) ◽

pp. 383-387 ◽

Cited By ~ 36

Author(s):

Raymond A.A. Smith ◽

Kate Meade ◽

Claire E. Pickford ◽

Rebecca J. Holley ◽

Catherine L.R. Merry

Keyword(s):

Stem Cell ◽

Cell Differentiation ◽

Es Cells ◽

Three Dimensional ◽

Embryonic Stem ◽

Stem Cell Differentiation ◽

Cell Types ◽

Specific Pattern ◽

Embryonic Stem Cell Differentiation ◽

Specific Cell

ES (embryonic stem) cell differentiation is dependent on the presence of HS (heparan sulfate). We have demonstrated that, during differentiation, the evolution of specific cell lineages is associated with particular patterns of GAG (glycosaminoglycan) expression. For example, different HS epitopes are synthesized during neural or mesodermal lineage formation. Cell lines mutant for various components of the HS biosynthetic pathway are selectively impaired in their differentiation, with lineage-specific effects observed for some lines. We have also observed that the addition of soluble GAG saccharides to cells, with or without cell-surface HS, can influence the pace and outcome of differentiation, again highlighting specific pattern requirements for particular lineages. We are combining this work with ongoing studies into the design of artificial cell environments where we have optimized three-dimensional scaffolds, generated by electrospinning or by the formation of hydrogels, for the culture of ES cells. By permeating these scaffolds with defined GAG oligosaccharides, we intend to control the mechanical environment of the cells (via the scaffold architecture) as well as their biological signalling environment (using the oligosaccharides). We predict that this will allow us to control ES cell pluripotency and differentiation in a three-dimensional setting, allowing the generation of differentiated cell types for use in drug discovery/testing or in therapeutics.

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