Expansion of Multipotent Stem Cells from the Adult Human Brain

Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard Kjesbu; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar O.; Palmero, Sheryl; Langmoen, Iver A.

doi:10.1371/journal.pone.0071334

Cited by 41 publications

(58 citation statements)

References 68 publications

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“…Comparison of transcriptome data and available data sets confirmed that all 3 types of somatic cells expressed a set of cell type specific markers. The n5-derived fibroblasts closely resembled MRC5 (human lung fibroblasts), BJ1 (human foreskin fibroblasts) and human skin fibroblasts; 20,21 the n5-derived neurons corresponded to the human gray and white matter brain cells; 22 and the transcriptome of our RPE cells was similar to previously published hRPE cells. 23,24,25 (for details see Supplemental Experimental Procedures Fig.…”

Section: Establishment Of the Hesm01-oskmn-dox Isogenic Systemsupporting

confidence: 66%

An integrative analysis of reprogramming in human isogenic system identified a clone selection criterion

et al. 2016

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Kiselev (2016) An integrative analysis of reprogramming in human isogenic system identified a clone selection criterion, Cell Cycle, 15:7, 986-997, DOI: 10.1080/15384101.2016 ABSTRACTThe pluripotency of newly developed human induced pluripotent stem cells (iPSCs) is usually characterized by physiological parameters; i.e., by their ability to maintain the undifferentiated state and to differentiate into derivatives of the 3 germ layers. Nevertheless, a molecular comparison of physiologically normal iPSCs to the "gold standard" of pluripotency, embryonic stem cells (ESCs), often reveals a set of genes with different expression and/or methylation patterns in iPSCs and ESCs. To evaluate the contribution of the reprogramming process, parental cell type, and fortuity in the signature of human iPSCs, we developed a complete isogenic reprogramming system. We performed a genome-wide comparison of the transcriptome and the methylome of human isogenic ESCs, 3 types of ESC-derived somatic cells (fibroblasts, retinal pigment epithelium and neural cells), and 3 pairs of iPSC lines derived from these somatic cells. Our analysis revealed a high input of stochasticity in the iPSC signature that does not retain specific traces of the parental cell type and reprogramming process. We showed that 5 iPSC clones are sufficient to find with 95% confidence at least one iPSC clone indistinguishable from their hypothetical isogenic ESC line. Additionally, on the basis of a small set of genes that are characteristic of all iPSC lines and isogenic ESCs, we formulated an approach of "the best iPSC line" selection and confirmed it on an independent dataset.

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Section: Establishment Of the Hesm01-oskmn-dox Isogenic Systemsupporting

confidence: 66%

An integrative analysis of reprogramming in human isogenic system identified a clone selection criterion

et al. 2016

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“…However, to our knowledge, the presence of a SOX2 + (SRY-like homeobox 2) glial progenitor subpopulation, which precedes the expression of these markers during the differentiation process to glial cells, has not been reported, although some preliminary studies claim the possibility of isolating SOX2 + cells from human white matter, among other brain regions [10]. This transcription factor plays critical roles throughout development and is required for the reprogramming of somatic cells in induced pluripotent cells (iPS) [11], [12].…”

Section: Introductionmentioning

confidence: 95%

SOX2+ Cell Population from Normal Human Brain White Matter Is Able to Generate Mature Oligodendrocytes

Cruz¹,

Carrión-Navarro²,

García-Romero

et al. 2014

PLoS ONE

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ObjectivesA number of neurodegenerative diseases progress with a loss of myelin, which makes them candidate diseases for the development of cell-replacement therapies based on mobilisation or isolation of the endogenous neural/glial progenitor cells, in vitro expansion, and further implantation. Cells expressing A2B5 or PDGFRA/CNP have been isolated within the pool of glial progenitor cells in the subcortical white matter of the normal adult human brain, all of which demonstrate glial progenitor features. However, the heterogeneity and differentiation potential of this pool of cells is not yet well established.MethodsWe used diffusion tensor images, histopathology, and immunostaining analysis to demonstrate normal cytoarchitecture and the absence of abnormalities in human temporal lobe samples from patients with mesial temporal sclerosis. These samples were used to isolate and enrich glial progenitor cells in vitro, and later to detect such cells in vivo.ResultsWe have identified a subpopulation of SOX2+ cells, most of them co-localising with OLIG2, in the white matter of the normal adult human brain in vivo. These cells can be isolated and enriched in vitro, where they proliferate and generate immature (O4+) and mature (MBP+) oligodendrocytes and, to a lesser extent, astrocytes (GFAP+).ConclusionOur results demonstrate the existence of a new glial progenitor cell subpopulation that expresses SOX2 in the white matter of the normal adult human brain. These cells might be of use for tissue regeneration procedures.

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“…A recent study has found that the generation and migration of new neurons is very much limited to the early childhood (Curtis et al, 2012). Less well-characterized in the human brain are proliferating NPCs in the hippocampus, white matter, and other regions, where cells isolated from the adult human brain are capable of generating both neurons and glia under culture conditions (Kukekov et al, 1999;Murrell et al, 2013;Nunes et al, 2003).…”

Section: Neurogenesis In the Human Brainmentioning

confidence: 99%

Stem Cell Therapy in Brain Trauma: Implications for Repair and Regeneration of Injured Brain in Experimental TBI Models

Rolfe¹,

Sun²

2015

Brain Neurotrauma

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Expansion of Multipotent Stem Cells from the Adult Human Brain

Cited by 41 publications

References 68 publications

An integrative analysis of reprogramming in human isogenic system identified a clone selection criterion

An integrative analysis of reprogramming in human isogenic system identified a clone selection criterion

SOX2+ Cell Population from Normal Human Brain White Matter Is Able to Generate Mature Oligodendrocytes

Stem Cell Therapy in Brain Trauma: Implications for Repair and Regeneration of Injured Brain in Experimental TBI Models

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