Lamin A/C Expression Is a Marker of Mouse and Human Embryonic Stem Cell Differentiation

Constantinescu, Dan; Gray, Heather; Sammak, Paul J.; Schatten, Gerald; Csóka, Antonei B.

doi:10.1634/stemcells.2004-0159

Cited by 319 publications

(190 citation statements)

References 57 publications

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“…1C). An empirically fit exponential yields an effective time constant of 2.7 days for differentiation-associated stiffening of the nucleus relative to the cell body; this timescale appears roughly consistent with global changes in nucleoprotein expression such as lamins in ESCs (7,17). The limiting ratio for L nuc /L cell (i.e., nuclear:cytoplasmic stiffness) of Ϸ0.15 is also consistent with past measurements of relative nuclear compliance for other differentiated cells (18).…”

Section: Results and Analysissupporting

confidence: 80%

“…Stem cell nuclei are therefore said to be more plastic than fully differentiated cells (3). Major differences are indeed found in chromatin conformation (4,5), nuclear protein expression (6)(7)(8), and also DNA and histone modification (9). Differentiation further entails immobilization of some nucleoplasmic proteins and is said to functionally ''rigidify'' the genome, setting a relatively permanent preference for particular expression profiles (10,11).…”

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confidence: 99%

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Physical plasticity of the nucleus in stem cell differentiation

Pajerowski

Dahl²,

Zhong³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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768

786

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Cell differentiation in embryogenesis involves extensive changes in gene expression structural reorganization within the nucleus, including chromatin condensation and nucleoprotein immobilization. We hypothesized that nuclei in naive stem cells would therefore prove to be physically plastic and also more pliable than nuclei in differentiated cells. Micromanipulation methods indeed show that nuclei in human embryonic stem cells are highly deformable and stiffen 6-fold through terminal differentiation, and that nuclei in human adult stem cells possess an intermediate stiffness and deform irreversibly. Because the nucleo-skeletal component Lamin A/C is not expressed in either type of stem cell, we knocked down Lamin A/C in human epithelial cells and measured a deformability similar to that of adult hematopoietic stem cells. Rheologically, lamin-deficient states prove to be the most fluidlike, especially within the first Ϸ10 sec of deformation. Nuclear distortions that persist longer than this are irreversible, and fluorescence-imaged microdeformation with photobleaching confirms that chromatin indeed flows, distends, and reorganizes while the lamina stretches. The rheological character of the nucleus is thus set largely by nucleoplasm/chromatin, whereas the extent of deformation is modulated by the lamina. chromatin remodeling ͉ cell mechanics ͉ nuclear plasticity

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Section: Results and Analysissupporting

confidence: 80%

mentioning

confidence: 99%

Physical plasticity of the nucleus in stem cell differentiation

Pajerowski

Dahl²,

Zhong³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

768

786

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“…Mass spectrometry analysis of Nip1 immunoprecipitates identified new potential Nip1 partners, among them lamin A/C. Lamin A/C is not observed in undifferentiated or proliferative cells, but its expression is activated in neuronal lineages and cardiomyocytes differentiated from human embryonic stem cells and in all mature and nearly mature neurons (22,25,64,65). Previously, it has been shown that undifferentiated P19 pluripotent mouse embryonal carcinoma cells contain low steady-state levels of lamins A/C RNAs that begin to increase 48 h after treatment with retinoic acid (23,66).…”

Section: Discussionmentioning

confidence: 99%

“…The member of type V intermediate filaments, lamins, are involved in nuclear organization by forming structures intercalated between chromatin and the inner nuclear membrane, DNA replication, and transcription, which are related to cell differentiation (19 -21). The expression of A-type lamins (lamins A/C) is associated with differentiated tissue and was shown to be present in mature and nearly mature neurons of rat brain (22)(23)(24)(25)(26).…”

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confidence: 99%

Mammalian Numb-interacting Protein 1/Dual Oxidase Maturation Factor 1 Directs Neuronal Fate in Stem Cells

Kennedy¹,

Ostrakhovitch²,

Sandiford³

et al. 2010

Journal of Biological Chemistry

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In this study, we describe a role for the mammalian Numb-interacting protein 1 (Nip1) in regulation of neuronal differentiation in stem cells. The expression of Nip1 was detected in the developing mouse brain, embryonic stem cells, primary neuronal stem cells, and retinoic acid-treated P19 embryonal carcinoma cells. The highest expression of Nip1 was observed in undifferentiated neuronal stem cells and was associated with Duox1-mediated reactive oxygen species ROS production. Ectopic nip1 expression in P19 embryonal carcinoma cells induced neuronal differentiation, and this phenotype was also linked to elevated ROS production. The neuronal differentiation in nip1-overexpressing P19 cells was achieved in a retinoic acid-independent manner and was corroborated by an increase in the expression of the neuronal basic helixloop-helix transcription factors and neural-lineage cell markers. Furthermore, depletion of nip1 by short hairpin RNA led to a decrease in the expression of neuronal basic helix-loop-helix transcription factors and ROS. However, inhibition of ROS production in nip1-overexpressing P19 cells restricted but did not extinguish neuronal differentiation. Microarray and mass spectrometry analysis identified intermediate filaments as the principal cytoskeletal elements affected by up-regulation of nip1. We show here the first evidence for a functional interaction between Nip1 and a component of the nuclear lamina, lamin A/C. associated with a neuronal-specific phenotype. Taken together, our data reveal an important role for Nip1 in the guidance of neuronal differentiation through ROS generation and modulation of intermediate filaments and implicate Nip1 as a novel intrinsic regulator of neuronal cell fate.

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“…T-cells and B-cells express only lamins of type B. Undifferentiated human and mouse embryonic stem cells lack lamins A/C, but express lamins B1 and B2 [63]. B-type lamin is expressed throughout embryogenesis, whereas lamin A and lamin C are not expressed until the tissue differentiation stage of development [64].…”

Section: Discussionmentioning

confidence: 99%

The karyosphere capsule inRana temporariaoocytes contains structural and DNA-binding proteins

Ilicheva

Podgornaya

Bogolyubov

2018

Nucleus

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During the last stages of oogenesis, oocyte chromosomes condense and come close together, forming the so-called karyosphere. Karyosphere formation is accompanied by an essential decrease in transcriptional activity. In the grass frog Rana temporaria, the karyosphere is surrounded by an extrachromosomal capsule that separates the chromosomes from the rest of the nucleoplasm. The karyosphere capsule (KC) of R. temporaria has been investigated in detail at the ultrastructural level, but its protein composition remained largely unknown. We demonstrate here that nuclear actin, especially F-actin, as well as lamins A/C and B are the most abundant proteins of the KC. Key proteins of nuclear pore complexes, such as Nup93 and Nup35, are also detectable in the KC. New antibodies recognizing the telomere-binding protein TRF2 allowed us to localize TRF2 in nuclear speckles. We also found that the R. temporaria KC contains some proteins involved in chromatin remodeling, including topoisomerase II and ATRX. Thus, we believe that KC isolates the chromosomes from the rest of the nucleoplasm during the final period of oocyte growth (late diplotene) and represents a specialized oocyte nuclear compartment to store a variety of factors involved in nuclear metabolism that can be used in future early development.Abbreviations: BrUTP: 5-bromouridine 5’-triphosphate; CytD: cytochalasin D; IGCs: interchromatin granule clasters; IgG: immunoglobulin G; KC: karyosphere capsule; Mw: molecular weight; NE: nuclear envelope; PBS: phosphate buffered saline; SDS-PAGE: sodium dodecyl sulfate polyacrylamide gel electrophoresis; Topo II: topoisomerase II

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Lamin A/C Expression Is a Marker of Mouse and Human Embryonic Stem Cell Differentiation

Cited by 319 publications

References 57 publications

Physical plasticity of the nucleus in stem cell differentiation

Physical plasticity of the nucleus in stem cell differentiation

Mammalian Numb-interacting Protein 1/Dual Oxidase Maturation Factor 1 Directs Neuronal Fate in Stem Cells

The karyosphere capsule inRana temporariaoocytes contains structural and DNA-binding proteins

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