Fibroblast Growth Factor 4 and Its Novel Splice Isoform Have Opposing Effects on the Maintenance of Human Embryonic Stem Cell Self-Renewal

Mayshar, Yoav; Rom, Eran; Chumakov, Irina; Kronman, Achia; Yayon, Avner; Benvenisty, Nissim

doi:10.1634/stemcells.2007-1037

Cited by 61 publications

(46 citation statements)

References 48 publications

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“…Transcriptional profiling was used here to define the molecular signatures of VPCs and MPCs. The self-renewal property of stem cells is regulated by a multitude of genes, including FGF4 and telomerase (5,6). TERT and FGF4 did not differ in VPCs and MPCs, but whether this molecular characteristic is sufficient to control the kinetics of these PC classes, favoring in both cases the generation of daughter stem cells could not be established.…”

Section: Discussionmentioning

confidence: 93%

RETRACTED: Identification of a coronary vascular progenitor cell in the human heart

Bearzi

Leri

Monaco

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

185

164

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Primitive cells capable of generating small resistance arterioles and capillary structures in the injured myocardium have been identified repeatedly. However, these cells do not form large conductive coronary arteries that would have important implications in the management of the ischemic heart. In the current study, we determined whether the human heart possesses a class of progenitor cells that regulates the growth of endothelial cells (ECs) and smooth muscle cells (SMCs) and vasculogenesis. The expression of vascular endothelial growth-factor receptor 2 (KDR) was used, together with the stem cell antigen c-kit, to isolate and expand a resident coronary vascular progenitor cell (VPC) from human myocardial samples. Structurally, vascular niches composed of c-kit-KDR-positive VPCs were identified within the walls of coronary vessels. The VPCs were connected by gap junctions to ECs, SMCs, and fibroblasts that operate as supporting cells. In vitro, VPCs were self-renewing and clonogenic and differentiated predominantly into ECs and SMCs and partly into cardiomyocytes. To establish the functional import of VPCs, a critical stenosis was created in immunosuppressed dogs, and tagged human VPCs were injected in proximity to the constricted artery. One month later, there was an increase in coronary blood flow (CBF) distal to the stenotic artery, resulting in functional improvement of the ischemic myocardium. Regenerated large, intermediate, and small human coronary arteries and capillaries were found. In conclusion, the human heart contains a pool of VPCs that can be implemented clinically to form functionally competent coronary vessels and improve CBF in patients with ischemic cardiomyopathy.

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Section: Discussionmentioning

confidence: 93%

RETRACTED: Identification of a coronary vascular progenitor cell in the human heart

Bearzi

Leri

Monaco

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

185

164

View full text Add to dashboard Cite

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“…At the ligand level, alternative splicing of fgf4 and fgf8 pre-mRNA can generate protein variants with distinct biological activities (Fletcher et al, 2006;Guo and Li, 2007;Mayshar et al, 2008). In particular, two FGF8 isoforms, FGF8a and FGF8b, respectively, induce neural and mesodermal tissues in Xenopus embryos (Fletcher et al, 2006).…”

Section: Pqbp1 Regulates Alternative Splicing Of An Fgf Receptormentioning

confidence: 99%

The splicing factor PQBP1 regulates mesodermal and neural development through FGF signaling

Iwasaki

Thomsen

2014

Development

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Alternative splicing of pre-mRNAs is an important means of regulating developmental processes, yet the molecular mechanisms governing alternative splicing in embryonic contexts are just beginning to emerge. Polyglutamine-binding protein 1 (PQBP1) is an RNAsplicing factor that, when mutated, in humans causes Renpenning syndrome, an X-linked intellectual disability disease characterized by severe cognitive impairment, but also by physical defects that suggest PQBP1 has broader functions in embryonic development. Here, we reveal essential roles for PQBP1 and a binding partner, WBP11, in early development of Xenopus embryos. Both genes are expressed in the nascent mesoderm and neurectoderm, and morpholino knockdown of either causes defects in differentiation and morphogenesis of the mesoderm and neural plate. At the molecular level, knockdown of PQBP1 in Xenopus animal cap explants inhibits target gene induction by FGF but not by BMP, Nodal or Wnt ligands, and knockdown of either PQBP1 or WBP11 in embryos inhibits expression of fgf4 and FGF4-responsive cdx4 genes. Furthermore, PQBP1 knockdown changes the alternative splicing of FGF receptor-2 (FGFR2) transcripts, altering the incorporation of cassette exons that generate receptor variants (FGFR2 IIIb or IIIc) with different ligand specificities. Our findings may inform studies into the mechanisms underlying Renpenning syndrome.

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“…Pluripotent stem cells express many alternatively spliced mRNAs, including alternatively spliced isoforms of pivotal pluripotency genes such as SALL4 (Rao et al, 2010), POU5F1 (Takeda et al, 1992), NANOG (Das et al, 2011), NR2F2 (Rosa and Brivanlou, 2011), and FGF4 (Mayshar et al, 2008).…”

Section: Alternative Splicingmentioning

confidence: 99%

How microRNAs facilitate reprogramming to pluripotency

Anokye‐Danso

Snitow

Morrisey

2012

Journal of Cell Science

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SummaryThe ability to generate pluripotent stem cells from a variety of cell and tissue sources through the ectopic expression of a specific set of transcription factors has revolutionized regenerative biology. The development of this reprogramming technology not only makes it possible to perform basic research on human stem cells that do not have to be derived from embryos, but also allows patient-specific cells and tissues to be generated for therapeutic use. Optimizing this process will probably lead to a better and more efficient means of generating pluripotent stem cells. Here, we discuss recent findings that show that, in addition to transcription factors, microRNAs can promote pluripotent reprogramming and can even substitute for these pluripotency transcription factors in some cases. Taking into consideration that microRNAs have the potential to be used as small-molecule therapeutics, such findings open new possibilities for both pluripotent stem cell reprogramming and the reprogramming of cells into other cell lineages.

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Fibroblast Growth Factor 4 and Its Novel Splice Isoform Have Opposing Effects on the Maintenance of Human Embryonic Stem Cell Self-Renewal

Cited by 61 publications

References 48 publications

RETRACTED: Identification of a coronary vascular progenitor cell in the human heart

RETRACTED: Identification of a coronary vascular progenitor cell in the human heart

The splicing factor PQBP1 regulates mesodermal and neural development through FGF signaling

How microRNAs facilitate reprogramming to pluripotency

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