Random Mutagenesis, Clonal Events, and Embryonic or Somatic Origin Determine the mtDNA Variant Type and Load in Human Pluripotent Stem Cells.

In this study, we deep-sequenced the mtDNA of human embryonic and induced pluripotent stem cells (hESCs and hiPSCs) and their source cells and found that the majority of variants pre-existed in the cells used to establish the lines. Early-passage hESCs carried few and low-load heteroplasmic variants, similar to those identified in oocytes and inner cell masses. The number and heteroplasmic loads of these variants increased with prolonged cell culture.

CpG Island Methylation Correlates with the Use of Alternative Promoters for USP44 Gene Expression in Human Pluripotent Stem Cells and Testes.

Deubiquitinating enzymes may play a major regulatory role in pluripotent stem cells (PSCs), but few studies have investigated this topic. Within this family of enzymes, we found that the ubiquitin-specific peptidase USP44, is highly expressed in embryonic stem cells, induced PSCs (iPSCs), and testes as compared with differentiated progenies and somatic organs. Analysis by quantitative polymerase chain reaction and 5' RACE showed that alternate promoters are responsible for expression in PSCs and organs.

What is really driving cell-surface interactions? Layer-by-layer assembled films may help to answer questions concerning cell attachment and response to biomaterials.

Layer-by-layer (LbL) assembled multicomponent films offer the opportunity to control and to fine-tune cell attachment and behavior on solid surfaces [Layer-by-Layer Films for Biomedical Applications, edited by Picart et al. (Wiley, Weinheim, 2014) and El-Khouri et al., "Multifunctional layer-by-layer architectures for biological applications," in Functional Polymeric Ultrathin Films, edited by Advincula and Knoll (Wiley, Weinheim, 2011), Vol.

Efficient and cost-effective generation of mature neurons from human induced pluripotent stem cells.

For years, our ability to study pathological changes in neurological diseases has been hampered by the lack of relevant models until the recent groundbreaking work from Yamanaka's group showing that it is feasible to generate induced pluripotent stem cells (iPSCs) from human somatic cells and to redirect the fate of these iPSCs into differentiated cells. In particular, much interest has focused on the ability to differentiate human iPSCs into neuronal progenitors and functional neurons for relevance to a large number of pathologies including mental retardation and behavioral or degenerative syndromes. Current differentiation protocols are time-consuming and generate limited amounts of cells, hindering use on a large scale.

ONSL and OSKM cocktails act synergistically in reprogramming human somatic cells into induced pluripotent stem cells.

The advent of human induced pluripotent stem cells (hiPSC) is revolutionizing many research fields including cell-replacement therapy, drug screening, physiopathology of specific diseases and more basic research such as embryonic development or diseases modeling. Despite the large number of reports on reprogramming methods, techniques in use remain globally inefficient. We present here a new optimized approach to improve this efficiency.

The mammalian-specific Tex19.1 gene plays an essential role in spermatogenesis and placenta-supported development.

Study Question: What is the consequence of Tex19.1 gene deletion in mice?

Summary Answer: The Tex19.1 gene is important in spermatogenesis and placenta-supported development.

Neurons and cardiomyocytes derived from induced pluripotent stem cells as a model for mitochondrial defects in Friedreich's ataxia.

Friedreich's ataxia (FRDA) is a recessive neurodegenerative disorder commonly associated with hypertrophic cardiomyopathy. FRDA is due to expanded GAA repeats within the first intron of the gene encoding frataxin, a conserved mitochondrial protein involved in iron-sulphur cluster biosynthesis. This mutation leads to partial gene silencing and substantial reduction of the frataxin level.

Human induced pluripotent stem cells improve stroke outcome and reduce secondary degeneration in the recipient brain.

Human induced pluripotent stem cells (hiPSCs) are a most appealing source for cell replacement therapy in acute brain lesions. We evaluated the potential of hiPSC therapy in stroke by transplanting hiPSC-derived neural progenitor cells (NPCs) into the postischemic striatum. Grafts received host tyrosine hydroxylase-positive afferents and contained developing interneurons and homotopic GABAergic medium spiny neurons that, with time, sent axons to the host substantia nigra.

A dual role of linker histone H1.4 Lys 34 acetylation in transcriptional activation.

The linker histone H1 is a key player in chromatin organization, yet our understanding of the regulation of H1 functions by post-translational modifications is very limited. We provide here the first functional characterization of H1 acetylation. We show that H1.

Extended passaging increases the efficiency of neural differentiation from induced pluripotent stem cells.

Background: The use of induced pluripotent stem cells (iPSCs) for the functional replacement of damaged neurons and in vitro disease modeling is of great clinical relevance. Unfortunately, the capacity of iPSC lines to differentiate into neurons is highly variable, prompting the need for a reliable means of assessing the differentiation capacity of newly derived iPSC cell lines. Extended passaging is emerging as a method of ensuring faithful reprogramming.

Red blood cell generation from human induced pluripotent stem cells: perspectives for transfusion medicine.

Background: Ex vivo manufacture of red blood cells from stem cells is a potential means to ensure an adequate and safe supply of blood cell products. Advances in somatic cell reprogramming of human induced pluripotent stem cells have opened the door to generating specific cells for cell therapy. Human induced pluripotent stem cells represent a potentially unlimited source of stem cells for erythroid generation for transfusion medicine.

High-efficiency derivation of human embryonic stem cell lines following pre-implantation genetic diagnosis.

Pre-implantation genetic diagnosis allows the characterisation of embryos that carry a gene responsible for a severe monogenic disease and to transfer to the mother's uterus only the unaffected one(s). The genetically affected embryos can be used to establish human embryonic stem cell (hESC) lines. We are currently establishing a cell bank of ESC lines carrying specific disease-causing mutant genes.

The pluripotency-associated gene Dppa4 is dispensable for embryonic stem cell identity and germ cell development but essential for embryogenesis.

Dppa4 (developmental pluripotency-associated 4) has been identified in several high-profile screens as a gene that is expressed exclusively in pluripotent cells. It encodes a nuclear protein with an SAP-like domain and appears to be associated preferentially with transcriptionally active chromatin. Its exquisite expression pattern and results of RNA interference experiments have led to speculation that Dppa4, as well as its nearby homolog Dppa2, might play essential roles in embryonic stem (ES) cell function and/or germ cell development.

Functional neuronal differentiation of bone marrow-derived mesenchymal stem cells.

Recent results have shown the ability of bone marrow cells to migrate in the brain and to acquire neuronal or glial characteristics. In vitro, bone marrow-derived MSCs can be induced by chemical compounds to express markers of these lineages. In an effort to set up a mouse model of such differentiation, we addressed the neuronal potentiality of mouse MSCs (mMSCs) that we recently purified.

Development of gliomas: potential role of asymmetrical cell division of neural stem cells.

Asymmetrical cell division is a mechanism that gives rise to two daughter cells with different proliferative and differentiative fates. It occurs mainly during development and in adult stem cells. Accumulating evidence suggests that tumour cells arise from the transformation of normal stem cells.

Isolation and characterisation of mesenchymal stem cells from adult mouse bone marrow.

The future use of adult mesenchymal stem cells (MSCs) for human therapies depends on the establishment of preclinical studies with other mammals such as mouse. Surprisingly, purification and characterisation of murine MSCs were only poorly documented. The aim of this study was to purify mouse MSCs from adult bone marrow and to functionally characterise their abilities to differentiate along diverse lineages.

Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals.

Mesenchymal stem cells (MSCs) are largely studied for their potential clinical use. Recently, they have gained further interest after demonstration of an immunosuppressive role. In this study, we investigated whether in vivo injection of MSCs could display side effects related to systemic immunosuppression favoring tumor growth.