Cell differentiation inducers derived from thalidomide

Abstract The relationship between the kinetics of commitment to terminal cell differentiation and the rates of accumulation of globin mRNA has been examined during the induction of erythroid differentiation by polar/apolar chemical inducers in murine erythroleukemia cells (MELC), under conditions of more and less rapid commitment. Two differentiation inducers and three MELC variants have been studied. Hexamethylene bisacetamide (HMBA) initiates more rapid commitment than does dimethylsulfoxide (Me2SO). MELC variant DR10 is resistant to induction by Me2SO and responds sluggishly to HMBA, in comparison with the DS19- Sc9 variant. V3.17, an MELC variant resistant to low concentrations of vincristine, shows increased sensitivity to the inducers and an accelerated rate of commitment to terminal differentiation compared with DS19-Sc9. It is demonstrated that commitment and the actual expression of differentiation, as measured by the accumulation of alpha- , beta maj-, and beta min-globin mRNA, are temporally coordinated functions during induced differentiation of a transformed cell line by exposure to polar/apolar agents.

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Molecular recognition-directed site-specific release of stem cell differentiation inducers for enhanced joint repair

Biomaterials ◽

10.1016/j.biomaterials.2019.119644 ◽

2020 ◽

Vol 232 ◽

pp. 119644 ◽

Cited By ~ 2

Author(s):

Xuemin Liu ◽

Yunhua Chen ◽

Angelina S. Mao ◽

Chengkai Xuan ◽

Zhifang Wang ◽

...

Keyword(s):

Stem Cell ◽

Cell Differentiation ◽

Molecular Recognition ◽

Stem Cell Differentiation ◽

Site Specific ◽

Joint Repair ◽

Differentiation Inducers

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Enforced expression of the c-myc oncogene inhibits cell differentiation by precluding entry into a distinct predifferentiation state in G0/G1.

Molecular and Cellular Biology ◽

10.1128/mcb.8.4.1614 ◽

1988 ◽

Vol 8 (4) ◽

pp. 1614-1624 ◽

Cited By ~ 162

Author(s):

S O Freytag

Keyword(s):

Cell Cycle ◽

Cell Differentiation ◽

Transcriptional Control ◽

Normal Cells ◽

Myc Oncogene ◽

Rous Sarcoma ◽

Myc Gene ◽

High Concentrations ◽

Arrest Growth ◽

Differentiation Inducers

A broad base of data has implicated a role for the c-myc proto-oncogene in the control of the cell cycle and cell differentiation. To further define the role of myc in these processes, I examined the effect of enforced myc expression on several events that are thought to be important steps leading to the terminally differentiated state: (i) the ability to arrest growth in G0/G1, (ii) the ability to replicate the genome upon initiation of the differentiation program, and (iii) the ability to lose responsiveness to mitogens and withdraw from the cell cycle. 3T3-L1 preadipocyte cell lines expressing various levels of myc mRNA were established by transfection with a recombinant myc gene under the transcriptional control of the Rous sarcoma virus (RSV) promoter. Cells that expressed high constitutive levels of pRSVmyc mRNA arrested in G0/G1 at densities similar to those of normal cells at confluence. Upon initiation of the differentiation program, such cells traversed the cell cycle with kinetics similar to those of normal cells and subsequently arrested in G0/G1. Thus, enforced expression of myc had no effect on the ability of cells to arrest growth in G0/G1 or to replicate the genome upon initiation of the differentiation program. Cells were then tested for their ability to reenter the cell cycle upon exposure to high concentrations of serum and for their capacity to differentiate. In contrast to normal cells, cells expressing high constitutive levels of myc RNA reentered the cell cycle when challenged with 30% serum and failed to terminally differentiate. The block to differentiation could be reversed by high expression of myc antisense RNA, showing that the induced block was specifically due to enforced expression of pRSVmyc. These findings indicate that 3T3-L1 preadipocytes enter a specific state in G0/G1 after treatment with differentiation inducers, into which cells expressing high constitutive levels of myc RNA are precluded from entering. I propose that myc acts as a molecular switch and directs cells to a pathway that can lead to continued proliferation or to terminal differentiation.

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Engineering an enthesis-like graft for rotator cuff repair: An approach to fabricate highly biomimetic scaffold capable of zone-specifically releasing stem cell differentiation inducers

Bioactive Materials ◽

10.1016/j.bioactmat.2021.12.021 ◽

2022 ◽

Author(s):

Can Chen ◽

Qiang Shi ◽

Muzhi Li ◽

Yang Chen ◽

Tao Zhang ◽

...

Keyword(s):

Stem Cell ◽

Cell Differentiation ◽

Rotator Cuff ◽

Rotator Cuff Repair ◽

Stem Cell Differentiation ◽

Biomimetic Scaffold ◽

Differentiation Inducers ◽

Cuff Repair

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Abstract 2198: ERK5 inhibition potentiates the effects of leukemia cell differentiation inducers by augmenting the function of master transcription factors

10.1158/1538-7445.am2015-2198 ◽

2015 ◽

Author(s):

Ruifang Zheng ◽

George Studzinski

Keyword(s):

Transcription Factors ◽

Cell Differentiation ◽

Leukemia Cell ◽

Differentiation Inducers

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Decellularized Cell Culture ECMs Act as Cell Differentiation Inducers

Stem Cell Reviews and Reports ◽

10.1007/s12015-020-09963-y ◽

2020 ◽

Vol 16 (3) ◽

pp. 569-584 ◽

Cited By ~ 1

Author(s):

Mahmut Parmaksiz ◽

Ayşe Eser Elçin ◽

Yaşar Murat Elçin

Keyword(s):

Cell Culture ◽

Cell Differentiation ◽

Differentiation Inducers

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Transient Glutathione Depletion Determines Terminal Differentiation in HL-60 Cells

Oxidative Medicine and Cellular Longevity ◽

10.4161/oxim.3.1.10405 ◽

2010 ◽

Vol 3 (1) ◽

pp. 53-60 ◽

Cited By ~ 14

Author(s):

Suzanne M. Krance ◽

Peter C. Keng ◽

James Palis ◽

Nazzareno Ballatori

Keyword(s):

Cell Differentiation ◽

Glutathione Depletion ◽

Low Doses ◽

Superoxide Anion Production ◽

Dihydroxyvitamin D3 ◽

All Trans Retinoic Acid ◽

Presence And Absence ◽

Nbt Reduction ◽

Differentiation Inducers

To better define the role of glutathione (GSH) in cell differentiation, the present study measured GSH concentrations during terminal HL-60 cell differentiation, in the presence and absence of differentiation-inducing agents, and in the presence and absence of GSH altering agents. Interestingly, there was a small transient increase in intracellular GSH levels during dimethyl sulfoxide (DMSO) or 1α,25-dihydroxyvitamin D3 (VD3) induced differentiation. This increase coincided with an increase in nitroblue tetrazolium (NBT) reduction capacity, a measure of superoxide anion production, but there was no apparent change in the GSH/glutathione disulfide (GSSG) ratio. Surprisingly, treatment of cells with low doses of 1-chloro-2,4-dinitrobenzene (CDNB; 5 µM) or diethylmaleate (DEM; 0.5 mM), which transiently deplete GSH levels to about 40% of control levels, resulted in enhanced differentiation of HL-60 cells exposed to VD3 or all-trans-retinoic acid (ATRA), as well as under un-induced conditions (i.e., spontaneous differentiation). Enhanced differentiation occurred when cells were treated with the GSH-depleting agents 4 hours after treatment with differentiation inducers. These findings indicate that intracellular GSH levels are regulated in a complex fashion during HL-60 cell differentiation, and that transient GSH depletion using low doses of CDNB and DEM enhances the differentiation process.

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