TGF β1 induces multiple independent signals to regulate human trophoblastic differentiation: mechanistic insights

Rama, Sylvain; Suresh, Y; Rao, A Jagannadha

doi:10.1016/s0303-7207(03)00202-8

Cited by 36 publications

(32 citation statements)

References 64 publications

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“…Differentiation into the transport lineage by TGF-b has been reported in both humans and rodents [13,15,26,88,89]. Even though the intracellular mediators guiding trophoblast differentiation and Id2 downregulation in response to TGF-b are still being investigated, studies in .…”

Section: Discussionmentioning

confidence: 99%

“…In rodents, the placenta comprises two zones: the junctional zone and the labyrinth. The placenta is further subdivided into three predominant cell lineages: labyrinthine cells, spongiotrophoblasts, and trophoblast giant cells [3,6,[12][13][14]. Different trophoblast lineages are derived via differentiation of trophoblast progenitor cells that perform specialized functions during gestation [3][4][5]12].…”

Section: Introductionmentioning

confidence: 99%

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Id2 Mediates Differentiation of Labyrinthine Placental Progenitor Cell Line, SM10

Selesniemi

Albers

Brown

2016

Stem Cells and Development

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The placenta is an organ that is formed transiently during pregnancy, and appropriate placental development is necessary for fetal survival and growth. Proper differentiation of the labyrinthine layer of the placenta is especially crucial, as it establishes the fetal-maternal interface that is involved in physiological exchange processes. Although previous studies have indicated the importance of inhibitor of differentiation/inhibitor of DNA binding-2 (Id2) helix-loop-helix transcriptional regulator in mediating cell differentiation, the ability of Id2 to regulate differentiation toward the labyrinthine (transport) lineage of the placenta has yet to be determined. In the current study, we have generated labyrinthine trophoblast progenitor cells with increased (SM10-Id2) or decreased (SM10-Id2-shRNA) Id2 expression and determined the effect on TGF-b-induced differentiation. Our Id2 overexpression and knockdown analyses indicate that Id2 mediates TGF-b-induced morphological differentiation of labyrinthine trophoblast cells, as Id2 overexpression prevents differentiation and Id2 knockdown results in differentiation. Thus, our data indicate that Id2 is an important molecular mediator of labyrinthine trophoblast differentiation. An understanding of the regulators of trophoblast progenitor differentiation toward the labyrinthine lineage may offer insights into events governing pregnancy-associated disorders, such as placental insufficiency, fetal growth restriction, and preeclampsia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Id2 Mediates Differentiation of Labyrinthine Placental Progenitor Cell Line, SM10

Selesniemi

Albers

Brown

2016

Stem Cells and Development

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“…p16 INK4a has earlier been shown to be associated with induction of squamous cell differentiation in normal human epidermal keratinocytes, but overexpression of p16 INK4a did not induce differentiation in the same cells. 25 In a human trophoblast cell line, p16 INK4a is upregulated during TGFb1-induced differentiation 26 and in K562 cells forced p16 INK4a expression promoted erythroid differentiation, 27 suggesting that p16 INK4a is involved in differentiation in different cell types. In summary, we have shown that p16 INK4a is expressed in cancerous and precancerous lesions of the skin and by specifically studying phosphorylation of Rb in parallel with p16 INK4a and proliferation shown that both squamous cell carcinoma in situ and invasive squamous cell carcinoma have a nonfunctional Rb-pathway but with partially contrasting etiologies.…”

Section: Discussionmentioning

confidence: 99%

Retinoblastoma protein function and p16INK4a expression in actinic keratosis, squamous cell carcinoma in situ and invasive squamous cell carcinoma of the skin and links between p16INK4a expression and infiltrative behavior

2004

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p16 INK4a is involved in many important regulatory events in the cell and the expression and function is closely associated with the retinoblastoma protein (Rb). Earlier, we have in colorectal cancer and in basal cell carcinoma showed that p16 INK4a is upregulated at the invasive front causing cell cycle arrest in infiltrative tumor cells via a functional Rb. This role for p16 INK4a as a regulator of proliferation when tumor cells infiltrate might besides a general cyclin-dependent kinase (cdk) inhibitory effect explain why p16 INK4a is deregulated in many tumor forms. The expression pattern of p16 INK4a in relation to Rb-function in squamous cancer and precancerous forms of the skin has not been fully detailed. We therefore characterized the expression of p16 INK4a , Rb-phosphorylation and proliferation in actinic keratosis, squamous cell carcinoma in situ and invasive squamous cell carcinoma with special reference to infiltrative behavior. The expression of p16 INK4a varied between the lesions, with weak and cytoplasmic p16 INK4a expression and functional Rb in actinic keratosis. Strong nuclear and cytoplasmic p16 INK4a expression was observed in all carcinomas in situ in parallel with lack of Rb-phosphorylation but high proliferation indicating a nonfunctional Rb. Invasive squamous carcinoma showed a mixed p16 INK4a expression pattern where some tumors had strong cytoplasmic p16 INK4a expression, large fraction of Rb-phosphorylated cells and high proliferation. Interestingly, despite this disability of p16 INK4a to inhibit proliferation there was an upregulation of cytoplasmic p16 INK4a in infiltrative cells compared to tumor cells towards the tumor center. A similar scenario but strong and combined nuclear and cytoplasmic p16 INK4a expression in infiltrative cells, was observed in other invasive squamous cancers. This suggests that the p16 INK4a upregulation in infiltrative cells is governed independently of the subcellular localization or of the potential to affect proliferation via Rb, and suggests a potentially proliferation independent function for p16 INK4a in infiltrative behavior.

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“…Ccna2 forms a complex with Cdk1 and enables the start of mitosis (G2 / M). Previous studies confimed the inhibitory effect of TGF-β1 on the expression of Cdk and Ccna2 (Rama et al 2003). Reduction in Ccna2 level, similar to described in cardiomyocytes, can prevent cell division and result in inhibition of myogenesis (Fajas et al 2001).…”

Section: Discussionmentioning

confidence: 82%

Transcriptional pattern of TGF-β1 inhibitory effect on mouse C2C12 myoblasts differentiation

Wicik¹,

Sadkowski²,

Jank³

et al. 2010

Polish Journal of Veterinary Sciences

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The aim of the present study was to define the effect of TGF-β1 on C2C12 myoblasts myogenesis. TGF-β1 together with its receptor is a negative auto-paracrine regulator of myogenesis, which influences the proliferation, differentiation, and functions of muscle cells. TGF-β1 exerts highly significant inhibitory effect on differentiation of C2C12 mouse myoblasts manifested by the impairment of cell fusion and very low expression of myosin heavy chain. The study of differentiating C2C12 mouse myoblasts treated with TGF-β1 revealed 502 genes (436 down-regulated and 66 up-regulated) with statistically different expression. TGF-β1-regulated genes were identified to be involved in 29 biological processes, 29 molecular functions groups and 59 pathways. The strongest inhibiting effect of TGF-β1 was observed in the cadherin and Wnt pathways. The key-genes that could play the role of TGF-β1 targets during myoblasts differentiation was identified such as: Max, Creb1, Ccna2, Bax, MdfI, Tef, Tubg1, Cxcl5, Rho, Calca and Lgals4.

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TGF β1 induces multiple independent signals to regulate human trophoblastic differentiation: mechanistic insights

Cited by 36 publications

References 64 publications

Id2 Mediates Differentiation of Labyrinthine Placental Progenitor Cell Line, SM10

Id2 Mediates Differentiation of Labyrinthine Placental Progenitor Cell Line, SM10

Retinoblastoma protein function and p16INK4a expression in actinic keratosis, squamous cell carcinoma in situ and invasive squamous cell carcinoma of the skin and links between p16INK4a expression and infiltrative behavior

Transcriptional pattern of TGF-β1 inhibitory effect on mouse C2C12 myoblasts differentiation

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