Autocrine transforming growth factor-β regulation of hematopoiesis: many outcomes that depend on the context

Ruscetti, Francis W.; Akel, Salem; Bartelmez, Stephen H.

doi:10.1038/sj.onc.1208921

Cited by 104 publications

(96 citation statements)

References 145 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although IFN is not usually detectable in normal plasma, human peripheral blood mononuclear cells have been shown to express low levels of IFN mRNA, 46 suggesting that a paracrine or an autocrine secretion of IFNa may also participate in this homeostatic regulation. Human stem and progenitor cell control by the TGF-b superfamily has been extensively studied in vitro with various cell types such as hHSCs, [25][26][27][28] keratinocytes, 29 and more recently, human adult embryonic stem cells (hESCs). [47][48][49][50][51][52][53] Our preliminary study of the effect of TGF-b on MSCs (data not shown) also indicates that blocking TGF-b can activate a subpopulation of highly proliferative progenitor cells.…”

Section: G12mentioning

confidence: 99%

“…3,[21][22][23] One group has also obtained differentiation into cells derived from ectoderm, such as neural cells 21 in mouse, or endoderm, such as functional hepatocyte-like cells in human. 24 The multifunctional cytokine transforming growth factor-b1 (TGF-b1) has been shown previously to play an important role in the regulation of the proliferation of stem cells in vitro, such as human hematopoietic stem cell (hHSC) subpopulations, [25][26][27][28] and primitive keratinocytes. 29 Thus, the use of antisense oligonucleotides has revealed that hHSC quiescence is mediated in part through an autocrine loop involving TGFb1.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A sub-population of high proliferative potential-quiescent human mesenchymal stem cells is under the reversible control of interferon α/β

et al. 2007

View full text Add to dashboard Cite

Type I interferon (IFN) is shown to control the reversible quiescence of a primitive human bone marrow mesenchymal stem cell (MSC) subpopulation. A 24 h pre-treatment of Stro1 þ / GlycoA-or CD45-/GlycoA-subpopulations with a monoclonal antibody (mAb) against the IFNAR1 chain of the human type I IFN receptor (64G12), or with a polyclonal anti-IFNa antibody, resulted in a marked increase in the number of very large colonies (CFU-F 43000 cells) obtained in the presence of low, but necessary, concentrations of bFGF. Over a 2-month culture period, this short activation promoted a faster and greater amplification of mesenchymal progenitors for adipocytes and osteoblasts. Activation correlated with inhibition of STAT1 and STAT2 phosphorylation and of STAT1 nuclear translocation. A non-neutralizing anti-IFNAR1 mAb was ineffective. We demonstrate that control and activated MSCs express ST3GAL3, a sialyltransferase necessary to produce the embryonic antigens SSEA-3 and -4. Interestingly, activated MSC progeny expressed SSEA-3 and -4 at a higher level than control cultures, but this was not correlated with a significant expression of other embryonic markers. As MSCs represent an essential tool in tissue regeneration, the use of 64G12, which rapidly recruits a higher number of primitive cells, might increase amplification safety for cell therapy.

show abstract

Section: G12mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A sub-population of high proliferative potential-quiescent human mesenchymal stem cells is under the reversible control of interferon α/β

et al. 2007

View full text Add to dashboard Cite

show abstract

“…[4][5][6] In vivo, TGF-b has a principal role as regulator of immune cell homeostasis and function, as unequivocally shown by the development of a lethal inflammatory disorder in both Tgf-b1-ligand and receptor knockout mice. [34][35][36] Furthermore, Tgf-b1 null mice exhibited enhanced myelopoiesis, suggesting that TGF-b acts as a negative regulator of myelopoiesis in vivo.…”

Section: Tgf-b: Lessons From In Vivo Modelsmentioning

confidence: 99%

“…2,3 A fundamental feature of the TGF-b superfamily is its highly pleiotropic nature, a phenomenon well illustrated within the hematopoietic system; depending on the differentiation stage and environmental context of the target cell, these factors can affect proliferation, differentiation and apoptosis either positively or negatively. [4][5][6] Part of the molecular basis for this is thought to stem from the unique repertoire of transcriptional co-factors expressed by each specific cellular target. The context-dependent actions of TGF-b ligands are reflected in vitro, often leading to opposing findings between in vitro and in vivo systems.…”

Section: Introductionmentioning

confidence: 99%

The role of Smad signaling in hematopoiesis and translational hematology

2011

View full text Add to dashboard Cite

Hematopoietic stem cells (HSCs) reside in the bone marrow (BM) of adult individuals and function to produce and regenerate the entire blood and immune system over the course of an individual's lifetime. Historically, HSCs are among the most thoroughly characterized tissue-specific stem cells. Despite this, the regulation of fate options, such as self-renewal and differentiation, has remained elusive, partly because of the expansive plethora of factors and signaling cues that govern HSC behavior in vivo. In the BM, HSCs are housed in specialized niches that dovetail the behavior of HSCs with the need of the organism. The Smad-signaling pathway, which operates downstream of the transforming growth factor-b (TGF-b) superfamily of ligands, regulates a diverse set of biological processes, including proliferation, differentiation and apoptosis, in many different organ systems. Much of the function of Smad signaling in hematopoiesis has remained nebulous due to early embryonic lethality of most knockout mouse models. However, recently new data have been uncovered, suggesting that the Smad-signaling circuitry is intimately linked to HSC regulation. In this review, we bring the Smad-signaling pathway into focus, chronicling key concepts and recent advances with respect to TGF-b-superfamily signaling in normal and leukemic hematopoiesis.

show abstract

“…6 TGF-β'nın paradoksal etkisi sadece solid tümörlerde değil, hematolojik malignitelerde de görülmektedir. 7,8 SMAD sinyal iletimindeki bozuklukların lökomogenez, almaç düzeyindeki değişikliklerin ve TGF-β etkinliğindeki artışın ise malign lenfoma (ML) gelişimi ile ilişkili olduğu bildirilmiştir. [8][9][10][11][12][13][14] Yukarıda belirtilen çalışmalar çoğunlukla eriş-kin hastalarda yapılmış olup, çocukluk çağı hematolojik maligniteleri ile TGF-β ilişkisine ait veriler kısıtlıdır.…”

unclassified

The İmportance of Serum Transforming Growth Factor-Beta 1 Levels in Pediatric Patients with Acute Leukemia and Malignant Lymphoma

Ödek¹,

Yavuz²,

Dinçaslan³

et al. 2016

Turkiye Klinikleri J Pediatr

View full text Add to dashboard Cite

Ö ÖZ ZE ET T A Am ma aç ç: : Dönüştürücü büyüme faktörü-beta [transforming growth faktör-beta (TGF-β)], hematolojik malignitelerin patogenezinde önemli rol oynamaktadır. Bu araştırmanın amacı, akut lösemi ve malign lenfoma tanısı almış çocuk hastalarda, tanı anındaki ve remisyondaki serum TGF-β1 düzeylerinin öneminin belirlenmesidir. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Ocak 2006-Aralık 2010 tarihleri arasında, Ankara Üniversitesi Tıp Fakültesi Çocuk Onkoloji Bilim Dalı'nda tanı alıp tedavisi yapılan 12 akut lösemi ve 16 malign lenfomalı hasta araştırmaya alındı. Serum TGF-β1 düzeyleri ELISA yöntemi ile belirlendi ve sonuçlar 20 sağlıklı kontrol ile karşılaştırıldı. B Bu ul lg gu ul la ar r: : Akut lösemi grubunda, tanı anındaki ortalama TGF-β1 düzeyi (8,067±3,820 pg/mL), remisyondaki (17,663±9,547 pg/mL) ve kontrol grubundakilere (21,565±7,910 pg/mL) göre istatistiksel olarak anlamlı şekilde düşük bulundu (sırasıyla p=0,015 ve p<0,001). Akut lösemi grubunda tanı anın-daki serum TGF-β1 düzeyleri ile beyaz küre, hemoglobin, trombosit ve laktat dehidrogenaz düzeyleri arasında ilişki saptanmadı. Hodgkin lenfoma grubunda, tanı anındaki ortalama TGF-β1 düzeyi (19,015±4,035 pg/mL) remisyondakine (22,942±6,805 pg/mL) göre düşük bulundu. Non-Hodgkin lenfoma grubunda ise tanı anın-daki ortalama TGF-β1 düzeyi (17,937±7,167 pg/mL) remisyondakine (16,055±7,435 pg/mL) göre yüksek bulundu. Hodgkin lenfoma ve non-Hodgkin lenfoma gruplarında tanı anı ve remisyondaki TGF-β1 düzeyleri arasında istatistiksel olarak anlamlı fark saptanmadı (sırasıyla p=0,173 ve 0,779). Malign lenfoma grubunda, tanı anındaki serum TGF-β1 düzeyleri ile eritrosit sedimentasyon hızı ve laktat dehidrogenaz düzeyleri arasında ilişki saptanmadı. S So on nu uç ç: : Akut lösemi grubunun tanı anındaki serum TGF-β1 düzeyi, remisyondaki ve kontrol grubundakilere göre anlamlı şekilde düşük saptanmıştır. Serum TGF-β1 düzeyinin, çocukluk çağı akut lösemilerinde tedaviye yanıtın izlenmesinde yararlı bir parametre olarak kullanılabileceği düşünülm-üştür.A An na ah h t ta ar r K Ke e l li i m me e l le er r: : Lösemi; lenfoma; dönüştürücü büyüme faktörü beta A AB BS S T TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Transforming growth factor-beta (TGF-β) seems to play an important role in the pathogenesis of hematological malignancies. The aim of this study was to evaluate the importance of serum levels of TGF-β1 in children with acute leukemia and malignant lymphoma at diagnosis and in remission. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : The serum levels of TGF-β1 were studied by ELISA in 12 children with acute leukemia and 16 children with malignant lymphoma who were diagnosed and treated at Ankara University Faculty of Medicine, Division of Pediatric Oncology between January 2006 and December 2010. Results were compared with 20 healthy controls. R Re es su ul lt ts s: : In acute leukemia group, the mean level of TGF-β1 at diagnosis (8.067±3.820 pg/mL) was significantly lower compared with patients in remission (17.663±9.547 pg/mL...

show abstract

Autocrine transforming growth factor-β regulation of hematopoiesis: many outcomes that depend on the context

Cited by 104 publications

References 145 publications

A sub-population of high proliferative potential-quiescent human mesenchymal stem cells is under the reversible control of interferon α/β

A sub-population of high proliferative potential-quiescent human mesenchymal stem cells is under the reversible control of interferon α/β

The role of Smad signaling in hematopoiesis and translational hematology

The İmportance of Serum Transforming Growth Factor-Beta 1 Levels in Pediatric Patients with Acute Leukemia and Malignant Lymphoma

Contact Info

Product

Resources

About