Individuality, Organisms, and Cell Differentiation

2018 ◽  
Author(s):  
Melinda Bonnie Fagan
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Blood Cells ◽  
Functional Integration ◽  
Model Organism ◽  
Model Organisms ◽  
Strong Version ◽  
Mammalian Development ◽  
Multicellular Organisms ◽  
Early Mammalian Development

This chapter builds on earlier arguments concerning the individuality of stem cells. The author has argued in previous work that stem cells are not biological individuals in the same way as specialized cells of multicellular organisms (e.g., neurons, red blood cells, muscle cells) but that some stem cells (cultured pluripotent stem cells) can be considered biological individuals by analogy with multicellular organisms. More precisely, the author claims that cultured pluripotent stem cells can be considered model organisms for studying early mammalian development. An important objection to this model organism thesis is that cultured pluripotent stem cells lack the organization (functional integration and cohesive unity) required for an entity to be an organism. This chapter explicates and rebuts a strong version of this objection and, in the process, clarifies the ontology of stem cells as experimental entities.

scholarly journals Inhibition of DYRK1A disrupts neural lineage specificationin human pluripotent stem cells

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Stephanie F Bellmaine ◽  
Dmitry A Ovchinnikov ◽  
David T Manallack ◽  
Claire E Cuddy ◽  
Andrew G Elefanty ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Gene Dosage ◽  
Gene Activation ◽  
Neural Induction ◽  
Neural Progenitor Cell ◽  
Human Pluripotent Stem Cells ◽  
Mammalian Development ◽  
Neural Lineage ◽  
Early Mammalian Development

Genetic analysis has revealed that the dual specificity protein kinase DYRK1A has multiple roles in the development of the central nervous system. Increased DYRK1A gene dosage, such as occurs in Down syndrome, is known to affect neural progenitor cell differentiation, while haploinsufficiency of DYRK1A is associated with severe microcephaly. Using a set of known and newly synthesized DYRK1A inhibitors, along with CRISPR-mediated gene activation and shRNA knockdown of DYRK1A, we show here that chemical inhibition or genetic knockdown of DYRK1A interferes with neural specification of human pluripotent stem cells, a process equating to the earliest stage of human brain development. Specifically, DYRK1A inhibition insulates the self-renewing subpopulation of human pluripotent stem cells from powerful signals that drive neural induction. Our results suggest a novel mechanism for the disruptive effects of the absence or haploinsufficiency of DYRK1A on early mammalian development, and reveal a requirement for DYRK1A in the acquisition of competence for differentiation in human pluripotent stem cells.

scholarly journals Metabolism in Pluripotent Stem Cells and Early Mammalian Development

2018 ◽  
Vol 27 (2) ◽  
pp. 332-338 ◽  
Author(s):  
Jin Zhang ◽  
Jing Zhao ◽  
Perrine Dahan ◽  
Vivian Lu ◽  
Cheng Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Mammalian Development ◽  
Early Mammalian Development

scholarly journals Umbilical Cord Tissue as a Source of Young Cells for the Derivation of Induced Pluripotent Stem Cells Using Non-Integrating Episomal Vectors and Feeder-Free Conditions

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 49
Author(s):  
Aisha Mohamed ◽  
Theresa Chow ◽  
Jennifer Whiteley ◽  
Amanda Fantin ◽  
Kersti Sorra ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Umbilical Cord ◽  
Pluripotent Stem Cells ◽  
Blood Cells ◽  
Growth Media ◽  
Donor Cells ◽  
Episomal Vectors ◽  
Umbilical Cord Tissue ◽  
Induced Pluripotent

The clinical application of induced pluripotent stem cells (iPSC) needs to balance the use of an autologous source that would be a perfect match for the patient against any safety or efficacy issues that might arise with using cells from an older patient or donor. Drs. Takahashi and Yamanaka and the Office of Cellular and Tissue-based Products (PMDA), Japan, have had concerns over the existence of accumulated DNA mutations in the cells of older donors and the possibility of long-term negative effects. To mitigate the risk, they have chosen to partner with the Umbilical Cord (UC) banks in Japan to source allogeneic-matched donor cells. Production of iPSCs from UC blood cells (UCB) has been successful; however, reprogramming blood cells requires cell enrichment with columns or flow cytometry and specialized growth media. These requirements add to the cost of production and increase the manipulation of the cells, which complicates the regulatory approval process. Alternatively, umbilical cord tissue mesenchymal stromal cells (CT-MSCs) have the same advantage as UCB cells of being a source of young donor cells. Crucially, CT-MSCs are easier and less expensive to harvest and grow compared to UCB cells. Here, we demonstrate that CT-MSCs can be easily isolated without expensive enzymatic treatment or columns and reprogramed well using episomal vectors, which allow for the removal of the reprogramming factors after a few passages. Together the data indicates that CT-MSCs are a viable source of donor cells for the production of clinical-grade, patient matched iPSCs.

Dna methylation of manufactured red blood cells from human induced pluripotent stem cells

2017 ◽  
Vol 53 ◽  
pp. S111-S112
Author(s):  
Isabel Dorn ◽  
Claudia Bernecker ◽  
Slave Trajanoski ◽  
Holm Zaehres ◽  
Peter Schlenke ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Red Blood Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Blood Cells ◽  
Induced Pluripotent

Generation of human induced pluripotent stem cells from a Bombay individual: Moving towards “universal-donor” red blood cells

2010 ◽  
Vol 391 (1) ◽  
pp. 329-334 ◽  
Author(s):  
Ali Seifinejad ◽  
Adeleh Taei ◽  
Mehdi Totonchi ◽  
Hamed Vazirinasab ◽  
Seideh Nafiseh Hassani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Red Blood Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Blood Cells ◽  
Induced Pluripotent ◽  
Universal Donor

scholarly journals Mammalian genes induce partially reprogrammed pluripotent stem cells in non-mammalian vertebrate and invertebrate species

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Ricardo Antonio Rosselló ◽  
Chun-Chun Chen ◽  
Rui Dai ◽  
Jason T Howard ◽  
Ute Hochgeschwender ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Mammalian Species ◽  
Embryonic Stem ◽  
Model Organisms ◽  
Differentiated Cells ◽  
Transcription Factor Genes ◽  
Induced Pluripotent

Cells are fundamental units of life, but little is known about evolution of cell states. Induced pluripotent stem cells (iPSCs) are once differentiated cells that have been re-programmed to an embryonic stem cell-like state, providing a powerful platform for biology and medicine. However, they have been limited to a few mammalian species. Here we found that a set of four mammalian transcription factor genes used to generate iPSCs in mouse and humans can induce a partially reprogrammed pluripotent stem cell (PRPSCs) state in vertebrate and invertebrate model organisms, in mammals, birds, fish, and fly, which span 550 million years from a common ancestor. These findings are one of the first to show cross-lineage stem cell-like induction, and to generate pluripotent-like cells for several of these species with in vivo chimeras. We suggest that the stem-cell state may be highly conserved across a wide phylogenetic range.

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