Small‐Molecule Regulators of Human Stem Cell Self‐Renewal

Bouchez, Laure C.; Boitano, Anthony E.; Lichtervelde, Lorenzo de; Romeo, Russell D.; Cooke, M.; Schultz, Peter G.

doi:10.1002/cbic.201000734

Cited by 17 publications

(10 citation statements)

References 36 publications

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“…Although pharmacological approaches to modulate SC fate have shown some promise (Angelos et al, 2017;Bouchez et al, 2011;Fares et al, 2014;Rentas et al, 2016), few studies have successfully modulated SC function by targeting autophagy. SMER28, a small molecule capable of inducing autophagy (Sarkar et al, 2007), has been used to reverse erythropoiesis abnormalities in patients with Diamond-Blackfan anaemia (DBA), a congenital disorder characterized by severely diminished red blood cell production due to defective erythroid progenitor differentiation (Doulatov et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Autophagy in stem cells: repair, remodelling and metabolic reprogramming

2018

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Autophagy is a catabolic pathway by which cellular components are delivered to the lysosome for degradation and recycling. Autophagy serves as a crucial intracellular quality control and repair mechanism but is also involved in cell remodelling during development and cell differentiation. In addition, mitophagy, the process by which damaged mitochondria undergo autophagy, has emerged as key regulator of cell metabolism. In recent years, a number of studies have revealed roles for autophagy and mitophagy in the regulation of stem cells, which represent the origin for all tissues during embryonic and postnatal development, and contribute to tissue homeostasis and repair throughout adult life. Here, we review these studies, focussing on the latest evidence that supports the quality control, remodelling and metabolic functions of autophagy during the activation, self-renewal and differentiation of embryonic, adult and cancer stem cells.

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Section: Discussionmentioning

confidence: 99%

Autophagy in stem cells: repair, remodelling and metabolic reprogramming

2018

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“…CH223191 was purchased from Tocris Bioscience (Ellisville, MO, USA). SR1 and SR2 compounds were prepared as described (Bouchez et al , 2011). …”

Section: Methodsmentioning

confidence: 99%

CXCR4 activation maintains a stem cell population in tamoxifen-resistant breast cancer cells through AhR signalling

et al. 2012

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Background:Tamoxifen is commonly used for breast cancer therapy. However, tamoxifen resistance is an important clinical problem. Continuous treatment with conventional therapy may contribute to cancer progression in recurring cancers through the accumulation of drug-resistant cancer progenitors.Methods:To investigate signalling mechanisms important for the maintenance and viability of drug-resistant cancer progenitors, we used microarray analysis, PCR array for genes involved in cancer drug resistance and metabolism, flow cytometry, soft agar colony formation assay, in vivo tumourigenicity assay and immunohistochemical analysis using tamoxifen-sensitive and tamoxifen-resistant breast cancer MCF7 cells.Results:Downregulation of CXCR4 signalling by small molecule antagonist AMD3100 specifically inhibits growth of progenitor cell population in MCF7(TAM-R) cells both in vitro and in vivo. Microarray analysis revealed aryl hydrocarbon receptor (AhR) signalling as one of the top networks that is differentially regulated in MCF7(TAM-R) and MCF7 xenograft tumours treated with AMD3100. Further, small molecule antagonists of AhR signalling specifically inhibit the progenitor population in MCF7(TAM-R) cells and growth of MCF7(TAM-R) xenografts in vivo.Conclusion:The chemokine receptor CXCR4 maintains a cancer progenitor population in tamoxifen-resistant MCF7 cells through AhR signalling and could be a putative target for the treatment of tamoxifen-resistant breast cancers.

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“…1A and fig. S1C), five of which were known [four (11, 12)] or previously unknown (one, UM125454, fig. S2) suppressors of the AhR pathway (Fig.…”

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confidence: 99%

Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal

Fares

Chagraoui

Gareau

et al. 2014

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The small number of hematopoietic stem and progenitor cells in cord blood units limits their widespread use in human transplant protocols. We identified a family of chemically related small molecules that stimulates the expansion ex vivo of human cord blood cells capable of reconstituting human hematopoiesis for at least 6 months in immunocompromised mice. The potent activity of these newly identified compounds, UM171 being the prototype, is independent of suppression of the aryl hydrocarbon receptor, which targets cells with more-limited regenerative potential. The properties of UM171 make it a potential candidate for hematopoietic stem cell transplantation and gene therapy.

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Small‐Molecule Regulators of Human Stem Cell Self‐Renewal

Cited by 17 publications

References 36 publications

Autophagy in stem cells: repair, remodelling and metabolic reprogramming

Autophagy in stem cells: repair, remodelling and metabolic reprogramming

CXCR4 activation maintains a stem cell population in tamoxifen-resistant breast cancer cells through AhR signalling

Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal

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