Regulation of human erythropoiesis by activin A, BMP2, and BMP4, members of the TGFβ family

Maguer-Satta, Véronique; Bartholin, Laurent; Jeanpierre, Sandrine; Ffrench, Martine; Martel, Sylvie; Magaud, Jean‐Pierre; Rimokh, Ruth

doi:10.1016/s0014-4827(02)00013-7

Cited by 91 publications

(104 citation statements)

References 45 publications

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“…25 However, recent studies have demonstrated that most BMP are pleiotropic regulators of embryonic and tissue development and functions, including hematopoiesis. [26][27][28] Our previous study demonstrated that PDGF enhanced the ex vivo expansion of NOD/SCID repopulating cells from cord blood CD34 þ cells. 15 A group of pleiotropic factors was detected in both AGM and C17.2 cells.…”

Section: Discussionmentioning

confidence: 99%

Multipotent neural precursors express neural and hematopoietic factors, and enhance ex vivo expansion of cord blood CD34+ cells, colony forming units and NOD/SCID-repopulating cells in contact and noncontact cultures

Lee

et al. 2004

Leukemia

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In view of the possible crosstalks between hematopoiesis and neuropoiesis, we evaluated two microenvironments, murine neonatal neural cell line C17.2 and primary embryonic aortagonad-mesonephros (AGM) stromal cells, on the ex vivo expansion of CD34 þ cells from human cord blood. In a contact culture system, C17.2 or AGM cells significantly enhanced the expansion of CD34 þ cells to a panel of early and committed hematopoietic progenitor cells. In a noncontact transwell system, pre-established C17.2 cells significantly increased the expansion of total nucleated cells, CD34 þ cells and multilineage colony forming cells (Po0.01). Expanded cells were infused into nonobese diabetic/severe-combined immunodeficient mice. The engraftment of human (hu)CD45 þ cells in the bone marrow of these mice was consistently higher in all the 10 experiments conducted with the support of C17.2 cells when compared with those in respective control groups (11.9 vs 2.43%, P ¼ 0.03). Using RT-PCR and Southern blot analysis, we showed that AGM and C17.2 cells expressed a panel of hematopoietic, bone morphogenetic and neurotrophic factors. Our data provided the first evidence on the promoting effects of a neural progenitor cell line on hematopoiesis at a noncontact condition. The mechanism could be mediated by the expression of multilineage regulatory factors.

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Section: Discussionmentioning

confidence: 99%

Multipotent neural precursors express neural and hematopoietic factors, and enhance ex vivo expansion of cord blood CD34+ cells, colony forming units and NOD/SCID-repopulating cells in contact and noncontact cultures

Lee

et al. 2004

Leukemia

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“…S7G-J). Activin A reduced the expansion of MPs during in vitro culture, while high levels of BMP4 slightly increased their proliferation (Maguer-Satta et al 2003;Jeanpierre et al 2008). Tricistron-transduced CD34 + HSPCs were resistant to both effects (Supplemental Fig.…”

Section: Cold Spring Harbor Laboratory Pressmentioning

confidence: 97%

miR-99a/100∼125b tricistrons regulate hematopoietic stem and progenitor cell homeostasis by shifting the balance between TGFβ and Wnt signaling

et al. 2014

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Although regulation of stem cell homeostasis by microRNAs (miRNAs) is well studied, it is unclear how individual miRNAs genomically encoded within an organized polycistron can interact to induce an integrated phenotype. miR-99a/100, let-7, and miR-125b paralogs are encoded in two tricistrons on human chromosomes 11 and 21. They are highly expressed in hematopoietic stem cells (HSCs) and acute megakaryoblastic leukemia (AMKL), an aggressive form of leukemia with poor prognosis. Here, we show that miR-99a/100~125b tricistrons are transcribed as a polycistronic message transactivated by the homeobox transcription factor HOXA10. Integrative analysis of global gene expression profiling, miRNA target prediction, and pathway architecture revealed that miR-99a/100, let-7, and miR-125b functionally converge at the combinatorial block of the transforming growth factor b (TGFb) pathway by targeting four receptor subunits and two SMAD signaling transducers. In addition, down-regulation of tumor suppressor genes adenomatous polyposis coli (APC)/APC2 stabilizes active b-catenin and enhances Wnt signaling. By switching the balance between Wnt and TGFb signaling, the concerted action of these tricistronic miRNAs promoted sustained expansion of murine and human HSCs in vitro or in vivo while favoring megakaryocytic differentiation. Hence, our study explains the high phylogenetic conservation of the miR-99a/100~125b tricistrons controlling stem cell homeostasis, the deregulation of which contributes to the development of AMKL.

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“…Multiple biological functions of activin A in a variety of cells and tissues have been described, including involvement in mesoder m induction [29] , stem cell biology [30] , reproductive biology [31] , erythroid differentiation [32] , systemic inflammation [33] , cell death induction [34] , wound healing [35] , and fibrosis [36] . Knock-out mice for activin beta A show severe defects in craniofacial development and die shortly after birth [37] .…”

Section: Dysfunctionmentioning

confidence: 99%

Activins and follistatins: Emerging roles in liver physiology and cancer

Kreidl

Öztürk²,

Metzner³

et al. 2009

WJH

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Activins are secreted proteins belonging to the TGF-β family of signaling molecules. Activin signals are crucial for differentiation and regulation of cell proliferation and apoptosis in multiple tissues. Signal transduction by activins relies mainly on the Smad pathway, although the importance of crosstalk with additional pathways is increasingly being recognized. Activin signals are kept in balance by antagonists at multiple levels of the signaling cascade. Among these, follistatin and FLRG, two members of the emerging family of follistatin-like proteins, can bind secreted activins with high affinity, thereby blocking their access to cell surface-anchored activin receptors. In the liver, activin A is a major negative regulator of hepatocyte proliferation and can induce apoptosis. The functions of other activins expressed by hepatocytes have yet to be more clearly defined. Deregulated expression of activins and follistatin has been implicated in hepatic diseases including inflammation, fibrosis, liver failure and primary cancer. In particular, increased follistatin levels have been found in the circulation and in the tumor tissue of patients suffering from hepatocellular carcinoma as well as in animal models of liver cancer. It has been argued that up-regulation of follistatin protects neoplastic hepatocytes from activin-mediated growth inhibition and apoptosis. The use of follistatin as biomarker for liver tumor development is impeded, however, due to the presence of elevated follistatin levels already during preceding stages of liver disease. The current article summarizes our evolving understanding of the multi-faceted activities of activins and follistatins in liver physiology and cancer.

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Regulation of human erythropoiesis by activin A, BMP2, and BMP4, members of the TGFβ family

Cited by 91 publications

References 45 publications

Multipotent neural precursors express neural and hematopoietic factors, and enhance ex vivo expansion of cord blood CD34+ cells, colony forming units and NOD/SCID-repopulating cells in contact and noncontact cultures

Multipotent neural precursors express neural and hematopoietic factors, and enhance ex vivo expansion of cord blood CD34+ cells, colony forming units and NOD/SCID-repopulating cells in contact and noncontact cultures

miR-99a/100∼125b tricistrons regulate hematopoietic stem and progenitor cell homeostasis by shifting the balance between TGFβ and Wnt signaling

Activins and follistatins: Emerging roles in liver physiology and cancer

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