Ras modulates commitment and maturation of 10T½ fibroblasts to adipocytes

1992 ◽  
Vol 70 (10-11) ◽  
pp. 1249-1257 ◽  
Author(s):  
Ying Lu ◽  
Steve Anderson ◽  
Michael J. Corbley ◽  
Yu-Chun Zhou ◽  
Hugh Pross ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Human Cancer ◽  
Low Frequency ◽  
Positive Association ◽  
Mesenchymal Cell ◽  
Negative Regulator ◽  
Ras Gene ◽  
Positive Role ◽  
Adipose Conversion ◽  
Differentiating Agent

The positive association of the ras oncogene with human cancer and the recognition that malignancy may, in part, represent the imbalance between cell proliferation and differentiation have generated intense interest in the potential role of ras in cell differentiation. We investigated this possibility utilizing as a model system the differentiation of the mesenchymal cell line C3H 10T½ (10T½) to adipocytes, and a series of transfectants of 10T½ cells in which the level of the ras gene product (p21ras; Ras) can be effectively up- or down-modulated. In agreement with previous reports, we found that 10T½ cultures, propagated in the resting state for several weeks, spontaneously convert to fat cells at a very low frequency. Downmodulation of endogenous p21ras levels, as a consequence of expression of antisense ras, markedly increased the rapidity and frequency of adipose conversion (6- to 10-fold), which was equivalent in magnitude to that effected by the potent differentiating agent 5-azacytidine. Conversely, overexpression of ras completely inhibited cell differentiation. In addition, adipocytes derived from antisense-ras expressing lines were characterized by a decrease in hormone responsiveness, as well as an apparent deficiency in attaining the terminally differentiated state. These findings suggest that Ras may be a negative regulator of the decision-making step of fibroblast differentiation to adipocytes. In addition, Ras may play an essential positive role in the transduction of hormonal signals necessary for full adipocytic maturation during later progression along the differentiation pathway.Key words: ras protooncogene, cell differentiation, signal transduction, insulin, adipocytes.

scholarly journals Aberrant PTEN expression in response to progesterone reduces endometriotic stromal cell apoptosis

Reproduction ◽  
2017 ◽  
Vol 153 (1) ◽  
pp. 11-21 ◽  
Author(s):  
JongYeob Choi ◽  
MinWha Jo ◽  
EunYoung Lee ◽  
Seongsoo Hwang ◽  
DooSeok Choi
Keyword(s):  
Stromal Cells ◽  
Human Cancer ◽  
Negative Regulator ◽  
Pten Expression ◽  
Endometrial Cell ◽  
Endometrial Stromal Cells ◽  
Human Cancer Cells ◽  
Subsequent Decrease ◽  
Autophagy Induction ◽  
Mtor Activity

In some human cancer cells, PTEN (phosphatase and tensin homolog deleted on chromosome 10) is known to regulate autophagy induction positively through the inhibition of PI3K/AKT pathway, leading to the activation of mTOR, a major negative regulator of autophagy. Recent studies reported that PTEN expression is abnormally decreased in endometriotic lesions. In endometriosis, abnormal PTEN expression may contribute to the alteration of endometrial cell autophagy, which may affect apoptosis because endometrial cell autophagy is directly involved in the regulation of apoptosis. To test this hypothesis, we evaluated the involvement of PTEN in the regulation of autophagy induction in human normal endometrial stromal cells (NESCs). In addition, we sought to determine whether aberrant PTEN expression in endometriotic cyst stromal cells (ECSCs) is associated with autophagy dysregulation, and a subsequent decrease in apoptosis. Our results show that PTEN expression was enhanced by progesterone treatment in NESCs. Subsequently, autophagy and apoptosis induction increased through the inhibition of AKT and mTOR activity. This progesterone-induced increase in apoptosis was reversed by the inhibition of autophagy induction using either mifepristone (progesterone receptor modulator) or PTEN inhibitor. In contrast, progesterone had no significant effects on PTEN expression, AKT, mTOR activity, autophagy or apoptosis in ECSCs. Furthermore, in contrast to normal eutopic endometrium, endometriotic tissues have constant PTEN expression, autophagy and apoptosis throughout the menstrual cycle. In conclusion, our results suggest abnormal PTEN expression in response to progesterone was observed in ECSCs, which led to the dysregulation of autophagy induction via AKT/mTOR signalling and a subsequent decrease in apoptosis.

Hes1 is a negative regulator of inner ear hair cell differentiation

Development ◽  
2000 ◽  
Vol 127 (21) ◽  
pp. 4551-4560 ◽  
Author(s):  
J.L. Zheng ◽  
J. Shou ◽  
F. Guillemot ◽  
R. Kageyama ◽  
W.Q. Gao
Keyword(s):  
Cell Differentiation ◽  
Hair Cell ◽  
Inner Ear ◽  
Cell Fate ◽  
Hair Cells ◽  
Outer Hair Cells ◽  
Negative Regulator ◽  
Pcr Analysis ◽  
Loss Of Function ◽  
Hair Cell Differentiation

Hair cell fate determination in the inner ear has been shown to be controlled by specific genes. Recent loss-of-function and gain-of-function experiments have demonstrated that Math1, a mouse homolog of the Drosophila gene atonal, is essential for the production of hair cells. To identify genes that may interact with Math1 and inhibit hair cell differentiation, we have focused on Hes1, a mammalian hairy and enhancer of split homolog, which is a negative regulator of neurogenesis. We report here that targeted deletion of Hes1 leads to formation of supernumerary hair cells in the cochlea and utricle of the inner ear. RT-PCR analysis shows that Hes1 is expressed in inner ear during hair cell differentiation and its expression is maintained in adulthood. In situ hybridization with late embryonic inner ear tissue reveals that Hes1 is expressed in supporting cells, but not hair cells, of the vestibular sensory epithelium. In the cochlea, Hes1 is selectively expressed in the greater epithelial ridge and lesser epithelial ridge regions which are adjacent to inner and outer hair cells. Co-transfection experiments in postnatal rat explant cultures show that overexpression of Hes1 prevents hair cell differentiation induced by Math1. Therefore Hes1 can negatively regulate hair cell differentiation by antagonizing Math1. These results suggest that a balance between Math1 and negative regulators such as Hes1 is crucial for the production of an appropriate number of inner ear hair cells.

scholarly journals Sufu regulation of Hedgehog signaling in P19 cells is required for proper glial cell differentiation

2021 ◽  
Author(s):  
Danielle M. Spice ◽  
Joshua Dierolf ◽  
Gregory M. Kelly
Keyword(s):  
Retinoic Acid ◽  
Cell Differentiation ◽  
Glial Cell ◽  
Neural Differentiation ◽  
Hedgehog Signaling ◽  
Target Genes ◽  
Cell Model ◽  
Ectopic Expression ◽  
Negative Regulator ◽  
Embryonal Carcinoma Cell

AbstractHedgehog signaling is essential for vertebrate development, however, less is known about the negative regulators that influence this pathway during the differentiation of cell fates. Using the mouse P19 embryonal carcinoma cell model, Suppressor of Fused (SUFU), a negative regulator of the Hedgehog pathway, was investigated during retinoic acid-induced neural differentiation. We found Hedgehog signaling was activated in the early phase of neural differentiation and became inactive during terminal differentiation of neurons and astrocytes. SUFU, which regulates signaling at the level of GLI, remained relatively unchanged during the differentiation process, however SUFU loss through CRISPIR-Cas9 gene editing resulted in decreased cell proliferation and ectopic expression of Hedgehog target genes. Interestingly, SUFU-deficient cells were unable to differentiate in the absence of retinoic acid, but when differentiated in its presence they showed delayed and decreased astrocyte differentiation; neuron differentiation did not appear to be affected. Retinoic acid-induced differentiation also caused ectopic activation of Hh target genes in SUFU-deficient cells and while the absence of the GLI3 transcriptional inhibitor suggested the pathway was active, no full-length GLI3 was detected even though the message encoding Gli3 was present. Thus, the study would indicate the proper timing and proportion of glial cell differentiation requires SUFU, and its normal regulation of GLI3 to maintain Hh signaling in an inactive state.

Type I collagen induces mesenchymal cell differentiation into myofibroblasts through YAP-induced TGF-β1 activation

Biochimie ◽  
2018 ◽  
Vol 150 ◽  
pp. 110-130 ◽  
Author(s):  
Xiaoling Liu ◽  
Xinyu Long ◽  
Weiwei Liu ◽  
Yeli Zhao ◽  
Toshihiko Hayashi ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Type I Collagen ◽  
Mesenchymal Cell ◽  
Type I ◽  
Tgf Β1

scholarly journals Mesenchymal cell differentiation and diseases: involvement of translin/TRAX complexes and associated proteins

2018 ◽  
Vol 1421 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Masataka Kasai ◽  
Reiko Ishida ◽  
Kazuhiko Nakahara ◽  
Ko Okumura ◽  
Katsunori Aoki
Keyword(s):  
Cell Differentiation ◽  
Mesenchymal Cell ◽  
Associated Proteins

scholarly journals Superoxide Mediates Shock Wave Induction of ERK-dependent Osteogenic Transcription Factor (CBFA1) and Mesenchymal Cell Differentiation toward Osteoprogenitors

2002 ◽  
Vol 277 (13) ◽  
pp. 10931-10937 ◽  
Author(s):  
Feng-Sheng Wang ◽  
Ching-Jen Wang ◽  
Shyr-Ming Sheen-Chen ◽  
Yur-Ren Kuo ◽  
Rong-Fu Chen ◽  
...  
Keyword(s):  
Shock Wave ◽  
Transcription Factor ◽  
Cell Differentiation ◽  
Mesenchymal Cell
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