Histone modifications and lamin A regulate chromatin protein dynamics in early embryonic stem cell differentiation

Melcer, Shai; Hezroni, Hadas; Rand, Eyal; Nissim-Rafinia, Malka; Skoultchi, Arthur I.; Stewart, Colin L.; Bustin, Michael; Meshorer, Eran

doi:10.1038/ncomms1915

Cited by 124 publications

(144 citation statements)

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“…Consistent with this function, histone acetylation is highly enriched in ESCs compared with differentiated cells [19,20,25,26], indicating that it contributes to the open chromatin state in ESCs. Consistently, treatments of HDAC inhibitors have been shown to enhance nuclear dynamics, reduce differentiation propensity [46] and support the selfrenewal program in ESCs [47]. In addition, in cell fusion-mediated reprogramming, low levels of histone H3 K9 acetylation (H3K9ac) in ESCs correlate with reduced efficiency in reprogramming the nuclei from fibroblasts, and HDAC inhibitors can improve the reprogramming efficiency [48].…”

Section: Histone Acetylationmentioning

confidence: 90%

“…*Enhanced effi- [197]; defect in neur- [197] ciency by Kmt1c oectoderm contribution inhibitor [73] in teratoma [46] Kmt1d/ NA Reduced NA NA Postimplantation Ehmt1/ efficiency [74] lethality (E8.5-9.5) Glp1 [197] Kmt1e/ NA Reduced Failure and acquiIncorporation to trophe-Peri-implantation Eset/ efficiency [74] sition of trophectctoderm upon blastocyst lethality (E3.5-5.5) the requirement growth rate [122] of Klf4 [74] [122]…”

Section: Introductionmentioning

confidence: 99%

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Embryonic stem cell and induced pluripotent stem cell: an epigenetic perspective

2012

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Section: Histone Acetylationmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Embryonic stem cell and induced pluripotent stem cell: an epigenetic perspective

2012

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“…9 Several studies have shown that patterns of histone modification have been associated with many essential biological processes, such as stem cell maintenance and differentiation. 10,16,21 Previous studies have revealed that mesenchymal stem cells exist in ligamentum flavum and play a crucial role in the development of OLF. 3,18 Whether histone modifications are involved in this ossification process has not been studied.…”

mentioning

confidence: 99%

Recombinant human bone morphogenetic protein-2–induced ossification of the ligamentum flavum in rats and the associated global modification of histone H3

Huang

Fan²,

Sun³

et al. 2014

SPI

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Object The primary object of this investigation was to study recombinant human bone morphogenetic protein–2 (rhBMP-2)–induced ossification of the ligamentum flavum and associated histone H3 modification in a rat model. In an additional set of studies the authors investigated spinal cord and behavioral changes in the same model. Methods The authors report on 2 separate sets of studies. A total of 90 rats were used for the 2 sets of studies (45 each); in each study, a lyophilized rhBMP-2 and collagen mixture (20 μg rhBMP-2 and 200 μl collagen) was implanted in the lumbar extradural space in 18 rats; another 18 animals were used for a sham-operation control group and underwent implantation of lyophilized collagen without rhBMP-2 at the same level; an additional 9 animals were used as untreated controls. Lumbar spinal samples were harvested from the rhBMP-2 groups and the shamoperation control groups at 1 week, 3 weeks, and 9 weeks after the operation. Samples were also obtained from untreated controls at the same time points. All samples were scanned using micro-CT and then made into paraffinembedded sections. The sections from the first set of 45 rats were stained using elastica van Gieson and toluidine blue, and the expression of histone modifications (H3K9ac, H3K18ac, H3K4me3, and H3K36me3) and osteogenic transcription factors (osterix, Runx2) was detected by immunohistochemistry. In the second set of studies, hindlimb motor function was assessed at 1 week, 3 weeks, and 9 weeks after surgery. After behavioral evaluation, samples were harvested, scanned using micro-CT, and then made into paraffin-embedded sections. The sections were stained using Luxol fast blue. The expression of NeuN was also detected using immunohistochemistry. Results Ossification was seen in the rhBMP-2 group from 1 week after insertion, and the volume of ossified mass increased at 3 and 9 weeks. There was no ossification seen in the sham-surgery and normal controls. The pathological changes of ossification involved ligament degeneration, cartilage formation, and, finally, bone replacement. Spinal cord evaluation showed a significant decrease in white matter content and number of neurons at 9 weeks after operation in the rhBMP-2–treated group (compared with findings in the sham-surgery and control groups as well as findings at the earlier time points in the rhBMP-2 group). Using immunohistochemical staining, histone modifications (H3K9ac, H3K18ac, H3K4me3, and H3K36me3) and osteogenic transcription factors (osterix, Runx2) all were found to be expressed in the fibrocartilage area of the rat ossified ligamentum flavum samples (rhBMP2 group). Conclusions This rhBMP-2–induced OLF is a typical endochondral ossification, which is similar to clinical OLF. The compressed spinal cord around the ossification site showed signs of a chronic degenerative process. Histone H3 modifications (H3K9ac, H3K18ac, H3K4me3, and H3K36me3) may play an important role in OLF.

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“…Since Lamin A/C has very low expression in ESCs, it has been suggested as a marker of differentiation. 23 The nuclei of hESCs are more deformable than their differentiated counterparts. Pajerowski et al used microaspiration to determine that the nuclei of hESCs stiffen by as much as sixfold as they reach terminal differentiation.…”

Section: Mechanical Properties Of Hpscsmentioning

confidence: 99%

Mechanobiology of Human Pluripotent Stem Cells

Earls

Jin

2013

Tissue Engineering Part B: Reviews

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Human pluripotent stem cells (hPSCs) are self-renewing and have the potential to differentiate into any cell type in the body, making them attractive cell sources for applications in tissue engineering and regenerative medicine. However, in order for hPSCs to find use in the clinic, the mechanisms underlying their self-renewal and lineage commitment must be better understood. Many technologies that have been developed for the maintenance and directed differentiation of hPSCs involve the use of soluble growth factors, but recent studies suggest that other elements of the hPSC microenvironment also influence the growth and differentiation of hPSCs. This includes the influences of cell-cell interactions, substrate mechanics, cellular interactions with extracellular matrix, as well as the nanotopography of the substrate and physical forces such as shear stress, cyclic mechanical strain, and compression. In this review, we highlight the recent progress of this area of research and discuss ways in which the mechanical cues may be incorporated into hPSC culture regimes to improve methods for expanding and differentiating hPSCs.

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Histone modifications and lamin A regulate chromatin protein dynamics in early embryonic stem cell differentiation

Cited by 124 publications

References 58 publications

Embryonic stem cell and induced pluripotent stem cell: an epigenetic perspective

Embryonic stem cell and induced pluripotent stem cell: an epigenetic perspective

Recombinant human bone morphogenetic protein-2–induced ossification of the ligamentum flavum in rats and the associated global modification of histone H3

Mechanobiology of Human Pluripotent Stem Cells

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