scholarly journals Chemically Induced Senescence in Human Stem Cell-Derived Neurons Promotes Phenotypic Presentation of Neurodegeneration

2021 ◽  
Author(s):  
Ali Fathi ◽  
Sakthikumar Mathivanan ◽  
Linghai Kong ◽  
Andrew J Petersen ◽  
Cole R.K Harder ◽  
...  
Keyword(s):  
Stem Cell ◽  
Small Molecules ◽  
Motor Neurons ◽  
Cortical Neurons ◽  
Axonal Degeneration ◽  
Human Stem Cell ◽  
Human Stem Cells ◽  
Embryonic Fibroblasts ◽  
Age Related ◽  
Chemically Induced

Modeling age-related neurodegenerative disorders with human stem cells is difficult due to the embryonic nature of stem cell derived neurons. We developed a chemical cocktail to induce senescence of iPSC-derived neurons to address this challenge. We first screened small molecules that induce embryonic fibroblasts to exhibit features characteristic of aged fibroblasts. We then optimized a cocktail of small molecules that induced senescence in fibroblasts and cortical neurons without causing DNA damage. The utility of the senescence cocktail was validated in motor neurons derived from ALS patient iPSCs which exhibited protein aggregation and axonal degeneration substantially earlier than those without cocktail treatment. Our senescence cocktail will likely enhance the manifestation of disease-related phenotypes in neurons derived from iPSCs, enabling the generation of reliable drug discovery platforms.

scholarly journals Pharmacological Profiling of Purified Human Stem Cell-Derived and Primary Mouse Motor Neurons

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Daniel Moakley ◽  
Joan Koh ◽  
Joao D. Pereira ◽  
Daniel M. DuBreuil ◽  
Anna-Claire Devlin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Motor Neurons ◽  
Human Stem Cell ◽  
Primary Mouse

scholarly journals Growing Glia: Cultivating Human Stem Cell Models of Gliogenesis in Health and Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Samantha N. Lanjewar ◽  
Steven A. Sloan
Keyword(s):  
Nervous System ◽  
Stem Cell ◽  
System Development ◽  
Stem Cell Differentiation ◽  
Nervous System Development ◽  
Model Systems ◽  
Human Stem Cell ◽  
Human Stem Cells ◽  
Health And Disease ◽  
Species Specific

Glia are present in all organisms with a central nervous system but considerably differ in their diversity, functions, and numbers. Coordinated efforts across many model systems have contributed to our understanding of glial-glial and neuron-glial interactions during nervous system development and disease, but human glia exhibit prominent species-specific attributes. Limited access to primary samples at critical developmental timepoints constrains our ability to assess glial contributions in human tissues. This challenge has been addressed throughout the past decade via advancements in human stem cell differentiation protocols that now offer the ability to model human astrocytes, oligodendrocytes, and microglia. Here, we review the use of novel 2D cell culture protocols, 3D organoid models, and bioengineered systems derived from human stem cells to study human glial development and the role of glia in neurodevelopmental disorders.

scholarly journals FUS is lost from nuclei and gained in neurites of motor neurons in a human stem cell model of VCP-related ALS

Brain ◽  
2020 ◽  
Author(s):  
Jasmine Harley ◽  
Cathleen Hagemann ◽  
Andrea Serio ◽  
Rickie Patani
Keyword(s):  
Stem Cell ◽  
Motor Neurons ◽  
Cell Model ◽  
Human Stem Cell ◽  
Stem Cell Model

scholarly journals Chemically induced senescence in human stem cell‐derived neurons promotes phenotypic presentation of neurodegeneration

Aging Cell ◽  
2021 ◽  
Author(s):  
Ali Fathi ◽  
Sakthikumar Mathivanan ◽  
Linghai Kong ◽  
Andrew J. Petersen ◽  
Cole R. K. Harder ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Stem Cell ◽  
Chemically Induced

The human stem cell hierarchy is defined by a functional dependence on Mcl-1 for self-renewal capacity

Blood ◽  
2010 ◽  
Vol 116 (9) ◽  
pp. 1433-1442 ◽  
Author(s):  
Clinton J. V. Campbell ◽  
Jung Bok Lee ◽  
Marilyne Levadoux-Martin ◽  
Tracy Wynder ◽  
Anargyros Xenocostas ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Functional Dependence ◽  
Family Members ◽  
Human Stem Cell ◽  
Human Stem Cells ◽  
Renewal Function ◽  
Self Renewal ◽  
Stem Cell Hierarchy

The molecular basis for the unique proliferative and self-renewal properties that hierarchically distinguish human stem cells from progenitors and terminally differentiated cells remains largely unknown. We report a role for the Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) as an indispensable regulator of self-renewal in human stem cells and show that a functional dependence on Mcl-1 defines the human stem cell hierarchy. In vivo pharmacologic targeting of the Bcl-2 family members in human hematopoietic stem cells (HSCs) and human leukemic stem cells reduced stem cell regenerative and self-renewal function. Subsequent protein expression studies showed that, among the Bcl-2 family members, only Mcl-1 was up-regulated exclusively in the human HSC fraction on in vivo regeneration of hematopoiesis. Short hairpin RNA–knockdown of Mcl-1 in human cord blood cells did not affect survival in the HSC or hematopoietic progenitor cell fractions in vitro but specifically reduced the in vivo self-renewal function of human HSCs. Moreover, knockdown of Mcl-1 in ontogenetically primitive human pluripotent stem cells resulted in almost complete ablation of stem cell self-renewal function. Our findings show that Mcl-1 is an essential regulator of stem cell self-renewal in humans and therefore represents an axis for therapeutic interventions.

Patentability of inventions involving human stem cells in Europe

10.5912/jcb6 ◽  
1969 ◽  
Vol 9 (1) ◽  
Author(s):  
Philippe Bouvet
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
European Patent ◽  
Patent Office ◽  
Human Stem Cell ◽  
Human Stem Cells ◽  
Ethical Aspects ◽  
Private Companies ◽  
European Group

In the last two years, research into stem cells has raised extraordinary therapeutic hopes – such as regenerative medicine – but also strong ethical questions. These questions have been fuelled by announcements, from private companies in particular, of the possibilities for human cloning. One of these questions relates to the patentability of inventions resulting from this area of research. In Europe this question is linked to the general debate surrounding the patentability of biological materials, such as genomic sequences. Although a large number of applications have been filed these last years, a few patents have already been issued. Some of them have been opposed at the European Patent Office. At the request of the European Commission, the European Group on Ethics (EGE) has prepared an opinion on ethical aspects of patenting inventions resulting from human stem cell research.

Abstract 307: Quantitative Characterization of the Contractile Architecture of Human Stem Cell Derived Cardiomyocytes

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Francesco S Pasqualini ◽  
Sean P Sheehy ◽  
Ashutosh Agarwal ◽  
Kevin K Parker
Keyword(s):  
Stem Cell ◽  
Small Molecules ◽  
Induced Pluripotent Stem Cell ◽  
Machine Learning Algorithms ◽  
Human Stem Cell ◽  
Quantitative Characterization ◽  
Cardiac Tissues ◽  
Induced Pluripotent ◽  
Processing Techniques

Human induced pluripotent stem cell derived cardiomyocytes (hiCMs) exhibit a fetal phenotype, but tools to quantify their relative immaturity are scarce. We reasoned that, during myocyte specification, cells progress through myofibrillogenesis as force-generating units, known as sarcomeres, self-assemble along the cell cytoskeleton. Therefore, we developed image processing techniques to quantitatively score myocyte structural phenotypes by the increasing degree of organization and alignment that sarcomeres acquire during myofibrillogenesis. Since this is a highly conserved process, quantifications obtained from α-actinin immunostains in rodent and hiCMs can be compared. Utilizing these metrics we quantitatively showed that hiCMs patterned on square fibronectin islands had significantly under-developed contractile architecture, in agreement with the qualitative observation that these cells retain a more migratory cytoskeleton. Furthermore, we trained thee independent machine learning algorithms on over 100 α-actin immunostains from engineered primary cardiac tissues at 6, 24 and 48 hours after seeding. These preparations were taken to represent differentiated, immature and mature structural architectures, respectively. After training,[[Unable to Display Character: ]]α-actinin immunostains of hiPS-derived cardiac tissues were unbiasedly analyzed by these classifiers. The results indicated that ~30% of cells exhibited cytoskeletal architectures similar to those of mature myocytes and that treatment with commercially available small molecules influence hiCM structural maturation. In conclusion, we provided metrics to assess the organization of the contractile cytoskeleton in primary and stem cell-derived cardiomyocytes and to unbiasedly quantify their maturation.

Chemically induced hepatotoxicity in human stem cell-induced hepatocytes compared with primary hepatocytes and HepG2

2016 ◽  
Vol 32 (5) ◽  
pp. 403-417 ◽  
Author(s):  
Seok-Jin Kang ◽  
Hyuk-Mi Lee ◽  
Young-Il Park ◽  
Hee Yi ◽  
Hunjoo Lee ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Stem Cell ◽  
Primary Hepatocytes ◽  
Chemically Induced
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