An Overview on Promising Somatic Cell Sources Utilized for the Efficient Generation of Induced Pluripotent Stem Cells

Ray, Arnab; Joshi, Jahnavy Madhukar; Sundaravadivelu, Pradeep Kumar; Raina, Khyati; Lenka, Nibedita; Kaveeshwar, Vishwas; Thummer, Rajkumar P.

doi:10.1007/s12015-021-10200-3

Cited by 30 publications

(32 citation statements)

References 224 publications

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“…If fibroblasts were to be homogenous, one would expect that each fibroblast would give rise to an iPSC clone with the same efficiency and regenerative potential. However, several studies report how reprogramming efficiency can vary across different experiments even when using the same batch of fibroblasts [ 20 ]. It would be interesting to explore whether fibroblasts expressing certain biomarkers would give rise to consistently stable iPSC colonies.…”

Section: Discussionmentioning

confidence: 99%

The Dynamic Nature of Human Dermal Fibroblasts Is Defined by Marked Variation in the Gene Expression of Specific Cytoskeletal Markers

Ahuja

Pontiggia

Moehrlen

et al. 2022

Life

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The evidence for fibroblast heterogeneity is continuously increasing, and recent work has shed some light on the existence of different sub-populations of fibroblasts in the human skin. Although we now have a more precise understanding of their distribution in the human body, we do not know whether their properties are predictive of where these cells derive from or whether these sub-types have functional consequences. In this study, we employed single-cell transcriptomics (10X Genomics) to study gene expression and segregate fibroblast sub-populations based on their genetic signature. We report the differential expression of a defined set of genes in fibroblasts from human skin, which may contribute to their dynamicity in vivo and in vitro. We show that the sub-population of fibroblasts expressing cytoskeletal markers, such as ANXA2, VIM, ACTB, are enriched in an adult skin sample. Interestingly, this sub-population of fibroblasts is not enriched in a neonatal skin sample but becomes predominant when neonatal fibroblasts are cultivated. On the other hand, the fibroblast sub-populations expressing COL1A1 and ELN are enriched in neonatal skin but are reduced in the adult skin and in fibroblasts from neonatal skin that are cultured in vitro. Our results indicate that fibroblasts are a dynamic cell type, and while their genetic make-up changes markedly, only a handful of genes belonging to the same functional pathway govern this alteration. The gene expression pattern of cytoskeletal markers may help in identifying whether the fibroblasts were isolated from an adult or an infant or whether they were cultivated, and this information could be useful for quality control in clinics and in cell banking. Furthermore, this study opens additional avenues to investigate the role of these markers in defining the complexity of human dermal fibroblasts.

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Section: Discussionmentioning

confidence: 99%

The Dynamic Nature of Human Dermal Fibroblasts Is Defined by Marked Variation in the Gene Expression of Specific Cytoskeletal Markers

Ahuja

Pontiggia

Moehrlen

et al. 2022

Life

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“…Most available and commonly used somatic cells include skin fibroblasts, hair keratinocytes, mononuclear cells from peripheral or umbilical cord blood (including B and T lymphocytes, and CD34 + cells), and urine cells containing renal tubular epithelial cells and fibroblast-like or urothelial cells. 7 Even cells harvested from biological waste materials were successfully used for reprogramming, including bone marrow cells, mesenchymal stem cells derived from fat tissue and teeth, liver and stomach cells, β-cells, melanocytes, or neural stem cells and progenitors 6 ( Fig. 1 ).…”

Section: Somatic Origin Of Human Ipscs and Reprogramming Methodsmentioning

confidence: 99%

“…1 ). This list of somatic cell sources is growing, including endothelial cells and cardiac progenitors from fetal tissues, 5 human anterior cruciate ligament cells, 8 myoblasts, ovarian follicular granulosa cells, amniotic fluid stem cells, and so on, 7 indicating that cells of almost all tissues can be used for the generation of iPSCs (for details, see Refs. 6 , 7 ).…”

Section: Somatic Origin Of Human Ipscs and Reprogramming Methodsmentioning

confidence: 99%

Human Induced Pluripotent Stem Cells: From Cell Origin, Genomic Stability, and Epigenetic Memory to Translational Medicine

2022

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The potential of human induced pluripotent stem cells (iPSCs) to self-renew indefinitely and to differentiate virtually into any cell type in unlimited quantities makes them attractive for in-vitro disease modeling, drug screening, personalized medicine, and regenerative therapies. As the genome of iPSCs thoroughly reproduces that of the somatic cells from which they are derived, they may possess genetic abnormalities, which would seriously compromise their utility and safety. Genetic aberrations could be present in donor somatic cells and then transferred during iPSC generation, or they could occur as de novo mutations during reprogramming or prolonged cell culture. Therefore, to warrant safety of human iPSCs for clinical applications, analysis of genetic integrity, particularly during iPSC generation and differentiation, should be carried out on a regular basis. On the other hand, reprogramming of somatic cells to iPSCs requires profound modifications in the epigenetic landscape. Changes in chromatin structure by DNA methylations and histone tail modifications aim to reset the gene expression pattern of somatic cells to facilitate and establish self-renewal and pluripotency. However, residual epigenetic memory influences the iPSC phenotype, which may affect their application in disease therapeutics. The present review discusses the somatic cell origin, genetic stability, and epigenetic memory of iPSCs and their impact on basic and translational research.

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“…Concerning the somatic cell source, pre-existing mutations acquired during the lifetime of the donor are more frequent in skin samples than in bone marrow. This means that very early life stage sources, for example those from umbilical cord blood banks, exhibit these potentially adverse events to a much lesser degree [ 63 , 64 , 65 , 66 ]. However, during the reprogramming, maintenance and scaling-up of iPSC cultures further mutations, including chromosomal rearrangements, can happen.…”

Section: Ipsc-derived Neuronsmentioning

confidence: 99%

Regenerative Neurology and Regenerative Cardiology: Shared Hurdles and Achievements

Mitrečić

Hribljan

Jagečić

et al. 2022

IJMS

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From the first success in cultivation of cells in vitro, it became clear that developing cell and/or tissue specific cultures would open a myriad of new opportunities for medical research. Expertise in various in vitro models has been developing over decades, so nowadays we benefit from highly specific in vitro systems imitating every organ of the human body. Moreover, obtaining sufficient number of standardized cells allows for cell transplantation approach with the goal of improving the regeneration of injured/disease affected tissue. However, different cell types bring different needs and place various types of hurdles on the path of regenerative neurology and regenerative cardiology. In this review, written by European experts gathered in Cost European action dedicated to neurology and cardiology-Bioneca, we present the experience acquired by working on two rather different organs: the brain and the heart. When taken into account that diseases of these two organs, mostly ischemic in their nature (stroke and heart infarction), bring by far the largest burden of the medical systems around Europe, it is not surprising that in vitro models of nervous and heart muscle tissue were in the focus of biomedical research in the last decades. In this review we describe and discuss hurdles which still impair further progress of regenerative neurology and cardiology and we detect those ones which are common to both fields and some, which are field-specific. With the goal to elucidate strategies which might be shared between regenerative neurology and cardiology we discuss methodological solutions which can help each of the fields to accelerate their development.

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An Overview on Promising Somatic Cell Sources Utilized for the Efficient Generation of Induced Pluripotent Stem Cells

Cited by 30 publications

References 224 publications

The Dynamic Nature of Human Dermal Fibroblasts Is Defined by Marked Variation in the Gene Expression of Specific Cytoskeletal Markers

The Dynamic Nature of Human Dermal Fibroblasts Is Defined by Marked Variation in the Gene Expression of Specific Cytoskeletal Markers

Human Induced Pluripotent Stem Cells: From Cell Origin, Genomic Stability, and Epigenetic Memory to Translational Medicine

Regenerative Neurology and Regenerative Cardiology: Shared Hurdles and Achievements

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