Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells

Williams, R.Lindsay; Hilton, Douglas J.; Pease, Shirley; Willson, Tracy A.; Stewart, Colin L.; Gearing, David P.; Wagner, Erwin F.; Metcalf, Donald; Nicola, Nicos A.; Gough, Nicholas M.

doi:10.1038/336684a0

Cited by 1,793 publications

(1,035 citation statements)

References 26 publications

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“…8 LIF activates a number of signaling pathways, one of which acts through activation and phosphorylation of STAT3 to maintain ESC selfrenewal. 9,10 pSTAT3 is a transcription factor that, when activated, dimerizes and translocates to the nucleus to activate transcription of its target genes.…”

Section: A Role For Polyamine Regulators In Esc Self-renewalmentioning

confidence: 99%

A role for polyamine regulators in ESC self-renewal

Zhao

Goh

et al. 2012

Cell Cycle

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E mbryonic stem cells (ESCs) dependon extensive regulatory networks to coordinate their self-renewal and differentiation. The polyamine pathway regulator AMD1 was recently implicated in ESC self-renewal and directed differentiation of ESCs to neural precursor cells (NPCs). The polyamines spermine and spermidine are essential for a wide range of biological processes, and their levels are tightly regulated. Here, we review the polyamine pathway and discuss how it can impact polyamine levels, cellular methylation and hypusinated EIF5A levels. We discuss how it could feed into regulation of ESC self-renewal and directed differentiation. We show that in addition to AMD1, a second rate-limiting enzyme in the polyamine pathway, ODC1, can also promote ESC self-renewal, and that both Amd1 and Odc1 can partially substitute for Myc during cellular reprogramming. We propose that both Amd1 and Odc1 are essential regulators of ESCs and function to ensure high polyamine levels to promote ESC self-renewal.

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Section: A Role For Polyamine Regulators In Esc Self-renewalmentioning

confidence: 99%

A role for polyamine regulators in ESC self-renewal

Zhao

Goh

et al. 2012

Cell Cycle

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“…Some of these factors have shown effects in other pluripotent cell populations. For instance, factors in the IL-6 family maintain the pluripotentiality of mouse embryonic stem (ES) cells through activation of the STAT3 pathway [22][23][24][25][26][27]. In addition, growth of human primordial germ cells requires LIF, SCF, and bFGF [28], whereas SCF, FLT3L, TPO, and IL-6 synergize with each other to promote expansion of hematopoietic progenitors [29][30][31][32][33][34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

Basic Fibroblast Growth Factor Supports Undifferentiated Human Embryonic Stem Cell Growth Without Conditioned Medium

et al. 2005

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Previous studies have shown that prolonged propagation of undifferentiated human embryonic stem cells (hESCs) requires conditioned medium from mouse embryonic feeders (MEF-CM) as well as matrix components. Because hESCs express growth factor receptors, including those for basic fibroblast growth factor (bFGF), stem cell factor (SCF), and fetal liver tyrosine kinase-3 ligand (Flt3L), we evaluated these and other growth factors for their ability to maintain undifferentiated hESCs in the absence of conditioned medium. We found cultures maintained in bFGF alone or in combination with other factors showed characteristics similar to MEF-CM control cultures, including morphology, surface marker and transcription factor expression, telomerase activity, differentiation, and karyotypic stability. In contrast, cells in media containing Flt-3L, thrombopoietin, and SCF, individually or in combination, showed almost complete differentiation after 6 weeks in culture. These data demonstrate that hESCs can be maintained in nonconditioned medium using growth factors. 2005;23:315-323 Stem Cells

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“…Thus ES cells have become invaluable in a number of experimental paradigms used for mouse transgenesis. LIF has been isolated and identified as the active factor in the fibroblast feeder layer (Williams et al, 1988). This factor was cloned and is now commercially available as ESgro.…”

Section: Discussionmentioning

confidence: 99%

Backtransplantation of chick cardiac neural crest cells cultured in LIF rescues heart development

Kirby

Kumiski

Myers

et al. 1993

Developmental Dynamics

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The cardiac neural crest is essential for normal development of the cardiovascular system. Cardiac neural crest cells are derived from the neural folds located between the mid-otic placodes and the caudal limit of somite 3. These crest cells can differentiate into a variety of mesenchymal cell types that support cardiovascular development, in addition to neurogenic cells. When cultured, many express a-smooth muscle actin or neurofilaments and lose their undifferentiated neural crest phenotype as shown by a decrease in HNK-1 reactivity. We wanted to determine whether cultured cardiac neural crest cells maintained the potency to support normal heart development when backtransplanted into embryos lacking their native cardiac neural crest. Under usual circumstances removal of the cardiac neural crest results in 80-100% incidence of persistent truncus arteriosus. The present study reports a system in which cardiac neural folds are cultured for 3 days and the cells backtransplanted into chick embryos after laser-induced ablation of the intrinsic cardiac neural folds, Rescue of heart development was improved 50% when cultured cells were backtransplanted and almost 200% when the backtransplanted cells had been cultured in leukemia inhibitory factor (LIF). To determine whether the cultured cells are capable of following normal migratory routes, cultured homospecific cardiac neural crest cells were tagged with DiI. Initially, fluorescent cells were found concentrated around the neural tube. By the second day following backtransplantation, the cells had migrated to the circumpharyngeal crest, populated the pharyngeal arches and aortic arch arteries, and were in the region of the cardiac outflow tract. By the third day, the labeled cells had dispersed, but could be found around the neural tube, esophagus, cardiac outflow tract, and within the dorsal root ganglia. Interestingly, a cranial migration to the periphery of the eyes was also noted. With the exception of the cranial migration to the eyes, cultured and backtransplanted cardiac neural crest cells followed normal migratory pathways to the cardiac outflow tract. LIF is used for the in vitro maintenance of the pluripotential phenotype of embryonic stem cells. In an effort to understand why LIF improves the ability of cul-tured neural crest cells to support normal heart development, we have examined the relationship of neural crest expression of HNK-1 antigen, a-smooth muscle actin, and neurofilament protein in neural crest cells cultured in LIF. LIF treatment resulted in an expanded period of expression of HNK-1 antigen, associated with a decrease in expression of a-smooth muscle actin. The expanded period of HNK-1 expression is associated with proliferation of the HNK-1 positive cell population. Expression of the neurofilament was the same in cells cultured with or without LIF.0 1993 Wiley-Liss, Inc.

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Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells

Cited by 1,793 publications

References 26 publications

A role for polyamine regulators in ESC self-renewal

A role for polyamine regulators in ESC self-renewal

Basic Fibroblast Growth Factor Supports Undifferentiated Human Embryonic Stem Cell Growth Without Conditioned Medium

Backtransplantation of chick cardiac neural crest cells cultured in LIF rescues heart development

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