scholarly journals Direct conversion of human fibroblasts into functional osteoblasts by defined factors

2015 ◽  
Vol 112 (19) ◽  
pp. 6152-6157 ◽  
Author(s):  
Kenta Yamamoto ◽  
Tsunao Kishida ◽  
Yoshiki Sato ◽  
Keisuke Nishioka ◽  
Akika Ejima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Bone Repair ◽  
Human Fibroblasts ◽  
Bone Matrix ◽  
Direct Conversion ◽  
Immunodeficient Mice ◽  
Similar Gene Expression Profile

Osteoblasts produce calcified bone matrix and contribute to bone formation and remodeling. In this study, we established a procedure to directly convert human fibroblasts into osteoblasts by transducing some defined factors and culturing in osteogenic medium. Osteoblast-specific transcription factors, Runt-related transcription factor 2 (Runx2), and Osterix, in combination with Octamer-binding transcription factor 3/4 (Oct4) and L-Myc (RXOL) transduction, converted ∼80% of the fibroblasts into osteocalcin-producing cells. The directly converted osteoblasts (dOBs) induced by RXOL displayed a similar gene expression profile as normal human osteoblasts and contributed to bone repair after transplantation into immunodeficient mice at artificial bone defect lesions. The dOBs expressed endogenous Runx2 and Osterix, and did not require continuous expression of the exogenous genes to maintain their phenotype. Another combination, Oct4 plus L-Myc (OL), also induced fibroblasts to produce bone matrix, but the OL-transduced cells did not express Osterix and exhibited a more distant gene expression profile to osteoblasts compared with RXOL-transduced cells. These findings strongly suggest successful direct reprogramming of fibroblasts into functional osteoblasts by RXOL, a technology that may provide bone regeneration therapy against bone disorders.

scholarly journals Cellular responses and gene expression profile changes due to bleomycin-induced DNA damage in human fibroblasts in space

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0170358 ◽  
Author(s):  
Tao Lu ◽  
Ye Zhang ◽  
Yared Kidane ◽  
Alan Feiveson ◽  
Louis Stodieck ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Human Fibroblasts ◽  
Cellular Responses ◽  
Profile Changes

scholarly journals Cultured Human Adipose Tissue Pericytes and Mesenchymal Stromal Cells Display a Very Similar Gene Expression Profile

2015 ◽  
Vol 24 (23) ◽  
pp. 2822-2840 ◽  
Author(s):  
Lindolfo da Silva Meirelles ◽  
Tathiane Maistro Malta ◽  
Virgínia Mara de Deus Wagatsuma ◽  
Patrícia Viana Bonini Palma ◽  
Amélia Goes Araújo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Gene Expression Profile ◽  
Mesenchymal Stromal Cells ◽  
Expression Profile ◽  
Stromal Cells ◽  
Human Adipose Tissue ◽  
Similar Gene Expression Profile ◽  
Similar Gene

scholarly journals Expression of Genes Related to Germ Cell Lineage and Pluripotency in Single Cells and Colonies of Human Adult Germ Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Sabine Conrad ◽  
Hossein Azizi ◽  
Maryam Hatami ◽  
Mikael Kubista ◽  
Michael Bonin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Adult Stem Cells ◽  
Single Cells ◽  
Human Fibroblasts ◽  
Embryonic Stem ◽  
Human Adult

The aim of this study was to elucidate the molecular status of single human adult germ stem cells (haGSCs) and haGSC colonies, which spontaneously developed from the CD49f MACS and matrix- (collagen−/laminin+ binding-) selected fraction of enriched spermatogonia. Single-cell transcriptional profiling by Fluidigm BioMark system of a long-term cultured haGSCs cluster in comparison to human embryonic stem cells (hESCs) and human fibroblasts (hFibs) revealed that haGSCs showed a characteristic germ- and pluripotency-associated gene expression profile with some similarities to hESCs and with a significant distinction from somatic hFibs. Genome-wide comparisons with microarray analysis confirmed that different haGSC colonies exhibited gene expression heterogeneity with more or less pluripotency. The results of this study confirm that haGSCs are adult stem cells with a specific molecular gene expression profilein vitro, related but not identical to true pluripotent stem cells. Under ES-cell conditions haGSC colonies could be selected and maintained in a partial pluripotent state at the molecular level, which may be related to their cell plasticity and potential to differentiate into cells of all germ layers.

scholarly journals The Repressor Element 1-Silencing Transcription Factor Regulates Heart-Specific Gene Expression Using Multiple Chromatin-Modifying Complexes

2007 ◽  
Vol 27 (11) ◽  
pp. 4082-4092 ◽  
Author(s):  
Andrew J. Bingham ◽  
Lezanne Ooi ◽  
Lukasz Kozera ◽  
Edward White ◽  
Ian C. Wood
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Cardiac Hypertrophy ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Molecular Mechanisms ◽  
Ventricular Myocytes ◽  
Specific Gene ◽  
Histone H4 Acetylation ◽  
Repressor Element

ABSTRACT Cardiac hypertrophy is associated with a dramatic change in the gene expression profile of cardiac myocytes. Many genes important during development of the fetal heart but repressed in the adult tissue are reexpressed, resulting in gross physiological changes that lead to arrhythmias, cardiac failure, and sudden death. One transcription factor thought to be important in repressing the expression of fetal genes in the adult heart is the transcriptional repressor REST (repressor element 1-silencing transcription factor). Although REST has been shown to repress several fetal cardiac genes and inhibition of REST function is sufficient to induce cardiac hypertrophy, the molecular mechanisms employed in this repression are not known. Here we show that continued REST expression prevents increases in the levels of the BNP (Nppb) and ANP (Nppa) genes, encoding brain and atrial natriuretic peptides, in adult rat ventricular myocytes in response to endothelin-1 and that inhibition of REST results in increased expression of these genes in H9c2 cells. Increased expression of Nppb and Nppa correlates with increased histone H4 acetylation and histone H3 lysine 4 methylation of promoter-proximal regions of these genes. Furthermore, using deletions of individual REST repression domains, we show that the combined activities of two domains of REST are required to efficiently repress transcription of the Nppb gene; however, a single repression domain is sufficient to repress the Nppa gene. These data provide some of the first insights into the molecular mechanism that may be important for the changes in gene expression profile seen in cardiac hypertrophy.

scholarly journals Neonatal and Adult CD4+CD3− Cells Share Similar Gene Expression Profile, and Neonatal Cells Up-Regulate OX40 Ligand in Response to TL1A (TNFSF15)

2006 ◽  
Vol 177 (5) ◽  
pp. 3074-3081 ◽  
Author(s):  
Mi-Yeon Kim ◽  
Kai-Michael Toellner ◽  
Andrea White ◽  
Fiona M. McConnell ◽  
Fabrina M. C. Gaspal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Ox40 Ligand ◽  
Similar Gene Expression Profile ◽  
Similar Gene

scholarly journals Identification of myeloid cells in the human enthesis as the main source of local IL-23 production

2019 ◽  
Vol 78 (7) ◽  
pp. 929-933 ◽  
Author(s):  
Charlie Bridgewood ◽  
Abdulla Watad ◽  
Tobias Russell ◽  
Timothy M Palmer ◽  
Helena Marzo-Ortega ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Cell Population ◽  
Expression Profile ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Ccr2 Gene ◽  
Similar Gene Expression Profile ◽  
Normal Human ◽  
Similar Gene

ObjectiveWe investigated whether the normal human spinal enthesis contained resident myeloid cell populations, capable of producing pivotal proinflammatory cytokines including tumour necrosis factor (TNF) and interleukin (IL)-23 and determined whether these could be modified by PDE4 inhibition.MethodsNormal human enthesis soft tissue (ST) and adjacent perientheseal bone (PEB) (n=15) were evaluated using immunohistochemistry (IHC), digested for myeloid cell phenotyping, sorted and stimulated with different adjuvants (lipopolysaccharide and mannan). Stimulated enthesis fractions were analysed for inducible production of spondyloarthropathy disease-relevant mediators (IL-23 full protein, TNF, IL-1β and CCL20). Myeloid populations were also compared with matched blood populations for further mRNA analysis and the effect of PDE4 inhibition was assessed.ResultsA myeloid cell population (CD45+ HLADR+ CD14+ CD11c+) phenotype was isolated from both the ST and adjacent PEB and termed ‘CD14+ myeloid cells’ with tissue localisation confirmed by CD14+ IHC. The CD14− fraction contained a CD123+ HLADR+ CD11c− cell population (plasmacytoid dendritic cells). The CD14+ population was the dominant entheseal producer of IL-23, IL-1β, TNF and CCL20. IL-23 and TNF from the CD14+ population could be downregulated by a PDE4I and other agents (histamine and 8-Bromo-cAMP) which elevate cAMP. Entheseal CD14+ cells had a broadly similar gene expression profile to the corresponding CD14+ population from matched blood but showed significantly lower CCR2 gene expression.ConclusionsThe human enthesis contains a CD14+ myeloid population that produces most of the inducible IL-23, IL-1β, TNF and CCL20. This population has similar gene expression profile to the matched blood CD14+ population.

Hepatic angiomyolipoma and hepatic stellate cells share a similar gene expression profile

2005 ◽  
Vol 36 (4) ◽  
pp. 341-347 ◽  
Author(s):  
Rajesh Kannangai ◽  
Anna Mae Diehl ◽  
Jason Sicklick ◽  
Marcus Rojkind ◽  
David Thomas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Hepatic Angiomyolipoma ◽  
Similar Gene Expression Profile ◽  
Similar Gene
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