Author
Jennifer Nichols
Other affiliations: University of Oxford, University of Edinburgh, Wellcome Trust Centre for Stem Cell Research ...read more
Bio: Jennifer Nichols is an academic researcher from University of Cambridge. The author has contributed to research in topics: Embryonic stem cell & Cellular differentiation. The author has an hindex of 61, co-authored 137 publications receiving 31645 citations. Previous affiliations of Jennifer Nichols include University of Oxford & University of Edinburgh.
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TL;DR: It is reported that the activity of Oct4 is essential for the identity of the pluripotential founder cell population in the mammalian embryo and also determines paracrine growth factor signaling from stem cells to the trophectoderm.
3,461 citations
TL;DR: These findings establish a central role for Nanog in the transcription factor hierarchy that defines ES cell identity and confirm that Cytokine dependence, multilineage differentiation, and embryo colonization capacity are fully restored upon transgene excision.
3,374 citations
TL;DR: It is shown that extrinsic stimuli are dispensable for the derivation, propagation and pluripotency of ES cells and reveal that ES cells have an innate programme for self-replication that does not require extrinsics instruction.
Abstract: In the three decades since pluripotent mouse embryonic stem (ES) cells were first described they have been derived and maintained by using various empirical combinations of feeder cells, conditioned media, cytokines, growth factors, hormones, fetal calf serum, and serum extracts. Consequently ES-cell self-renewal is generally considered to be dependent on multifactorial stimulation of dedicated transcriptional circuitries, pre-eminent among which is the activation of STAT3 by cytokines (ref. 8). Here we show, however, that extrinsic stimuli are dispensable for the derivation, propagation and pluripotency of ES cells. Self-renewal is enabled by the elimination of differentiation-inducing signalling from mitogen-activated protein kinase. Additional inhibition of glycogen synthase kinase 3 consolidates biosynthetic capacity and suppresses residual differentiation. Complete bypass of cytokine signalling is confirmed by isolating ES cells genetically devoid of STAT3. These findings reveal that ES cells have an innate programme for self-replication that does not require extrinsic instruction. This property may account for their latent tumorigenicity. The delineation of minimal requirements for self-renewal now provides a defined platform for the precise description and dissection of the pluripotent state.
3,250 citations
TL;DR: It is reported that bone morphogenetic proteins (BMPs) act in combination with LIF to sustain self-renewal and preserve multilineage differentiation, chimera colonization, and germline transmission properties.
2,233 citations
TL;DR: It is proposed that two phases of pluripotency can be defined: naive and primed, and this distinction extends to pluripotent stem cells derived from embryos or by molecular reprogramming ex vivo.
1,640 citations
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TL;DR: Induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions is demonstrated and iPS cells, designated iPS, exhibit the morphology and growth properties of ES cells and express ES cell marker genes.
23,959 citations
TL;DR: It is demonstrated that iPS cells can be generated from adult human fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc.
18,175 citations
TL;DR: Advances in the understanding of the mechanism and role of DNA methylation in biological processes are reviewed, showing that epigenetic mechanisms seem to allow an organism to respond to the environment through changes in gene expression.
Abstract: Cells of a multicellular organism are genetically homogeneous but structurally and functionally heterogeneous owing to the differential expression of genes. Many of these differences in gene expression arise during development and are subsequently retained through mitosis. Stable alterations of this kind are said to be 'epigenetic', because they are heritable in the short term but do not involve mutations of the DNA itself. Research over the past few years has focused on two molecular mechanisms that mediate epigenetic phenomena: DNA methylation and histone modifications. Here, we review advances in the understanding of the mechanism and role of DNA methylation in biological processes. Epigenetic effects by means of DNA methylation have an important role in development but can also arise stochastically as animals age. Identification of proteins that mediate these effects has provided insight into this complex process and diseases that occur when it is perturbed. External influences on epigenetic processes are seen in the effects of diet on long-term diseases such as cancer. Thus, epigenetic mechanisms seem to allow an organism to respond to the environment through changes in gene expression. The extent to which environmental effects can provoke epigenetic responses represents an exciting area of future research.
5,760 citations
TL;DR: It is demonstrated that two recently identified DNA methyltransferases, DnMT3a and Dnmt3b, are essential for de novo methylation and for mouse development and play important roles in normal development and disease.
5,708 citations
TL;DR: It is reported here that cells co-purifying with mesenchymal stem cells—termed here multipotent adult progenitor cells or MAPCs—differentiate, at the single cell level, not only into meschymal cells, but also cells with visceral mesoderm, neuroectoderm and endoderm characteristics in vitro.
Abstract: We report here that cells co-purifying with mesenchymal stem cells--termed here multipotent adult progenitor cells or MAPCs--differentiate, at the single cell level, not only into mesenchymal cells, but also cells with visceral mesoderm, neuroectoderm and endoderm characteristics in vitro. When injected into an early blastocyst, single MAPCs contribute to most, if not all, somatic cell types. On transplantation into a non-irradiated host, MAPCs engraft and differentiate to the haematopoietic lineage, in addition to the epithelium of liver, lung and gut. Engraftment in the haematopoietic system as well as the gastrointestinal tract is increased when MAPCs are transplanted in a minimally irradiated host. As MAPCs proliferate extensively without obvious senescence or loss of differentiation potential, they may be an ideal cell source for therapy of inherited or degenerative diseases.
5,475 citations