Topic
Cellular differentiation
About: Cellular differentiation is a research topic. Over the lifetime, 90966 publications have been published within this topic receiving 6099252 citations. The topic is also known as: Cellular differentiation & GO:0030154.
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TL;DR: It is shown that iPSCs obtained from mouse fibroblasts, hematopoietic and myogenic cells exhibit distinct transcriptional and epigenetic patterns, and it is demonstrated that cellular origin influences the in vitro differentiation potentials of iPSC into embryoid bodies and different hematopsic cell types.
Abstract: Induced pluripotent stem cells (iPSCs) have been derived from various somatic cell populations through ectopic expression of defined factors. It remains unclear whether iPSCs generated from different cell types are molecularly and functionally similar. Here we show that iPSCs obtained from mouse fibroblasts, hematopoietic and myogenic cells exhibit distinct transcriptional and epigenetic patterns. Moreover, we demonstrate that cellular origin influences the in vitro differentiation potentials of iPSCs into embryoid bodies and different hematopoietic cell types. Notably, continuous passaging of iPSCs largely attenuates these differences. Our results suggest that early-passage iPSCs retain a transient epigenetic memory of their somatic cells of origin, which manifests as differential gene expression and altered differentiation capacity. These observations may influence ongoing attempts to use iPSCs for disease modeling and could also be exploited in potential therapeutic applications to enhance differentiation into desired cell lineages.
1,147 citations
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TL;DR: An improved transcriptional regulator obtained through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to nuclease-null Cas9 is described and demonstrated in activating endogenous coding and noncoding genes and stimulating neuronal differentiation of human induced pluripotent stem cells (iPSCs).
Abstract: The RNA-guided nuclease Cas9 can be reengineered as a programmable transcription factor. However, modest levels of gene activation have limited potential applications. We describe an improved transcriptional regulator obtained through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to nuclease-null Cas9. We demonstrate its utility in activating endogenous coding and noncoding genes, targeting several genes simultaneously and stimulating neuronal differentiation of human induced pluripotent stem cells (iPSCs).
1,147 citations
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TL;DR: In this paper, the authors identify, isolate, and characterize the CSC population that drives and maintains hepatocellular carcinoma (HCC) growth and metastasis using a severe partial hepatectomy model.
1,147 citations
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TL;DR: One of the complementary DNA clones that was rapidly induced by NGF was found to have a nucleotide sequence that predicts a 54-kilodalton protein with homology to transcriptional regulatory proteins.
Abstract: Nerve growth factor (NGF) is a trophic agent that promotes the outgrowth of nerve fibers from sympathetic and sensory ganglia. The neuronal differentiation stimulated by this hormone was examined in the NGF-responsive cell line PC12. Differential hybridization was used to screen a complementary DNA library constructed from PC12 cells treated with NGF and cycloheximide. One of the complementary DNA clones that was rapidly induced by NGF was found to have a nucleotide sequence that predicts a 54-kilodalton protein with homology to transcriptional regulatory proteins. This clone, NGFI-A, contains three tandemly repeated copies of the 28- to 30-amino acid "zinc finger" domain present in Xenopus laevis TFIIIA and other DNA-binding proteins. It also contains another highly conserved unit of eight amino acids that is repeated at least 11 times. The NGFI-A gene is expressed at relatively high levels in the brain, lung, and superior cervical ganglion of the adult rat.
1,142 citations
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TL;DR: It is proposed that quiescent and active stem cell populations have separate but cooperative functional roles in a so-called “zoned” stem cell model.
Abstract: Adult stem cells are crucial for physiological tissue renewal and regeneration after injury. Prevailing models assume the existence of a single quiescent population of stem cells residing in a specialized niche of a given tissue. Emerging evidence indicates that both quiescent (out of cell cycle and in a lower metabolic state) and active (in cell cycle and not able to retain DNA labels) stem cell subpopulations may coexist in several tissues, in separate yet adjoining locations. Here, we summarize these findings and propose that quiescent and active stem cell populations have separate but cooperative functional roles.
1,142 citations