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Various stem cell signaling pathways influence stem cell generation, self-renewal and differentiation. In vivo, the microenvironment responsible for maintaining stem cells in pluripotent form and enabling their self-renewal is called the stem-cell niche.
|Cat. No.||Product Name / Activity|
|Selective Hsp90 inhibitor; protects neuroprogenitor cells against stress-induced apoptosis|
|Selective inhibitor of PTPMT1; maintains functional HSCs ex vivo|
|3299||AMD 3100 octahydrochloride|
|Highly selective CXCR4 antagonist; mobilizes hematopoietic stem cells in vivo|
|Maintains self-renewal and pluripotency of ESCs; potent inhibitor of GSK-3; also inhibits cdks|
|Integrin α4β1 inhibitor; mobilizes HSCs and progenitors|
|Selective GSK-3α/β inhibitor; inhibits CD8+ T cell effector differentiation|
|Preferentially mobilizes HSCs; dual α9β1/α4β1 integrin inhibitor|
|Cdc42 GTPase inhibitor; functionally rejuvenates aged HSCs|
|Hedgehog pathway antagonist; inhibits ciliogenesis|
|Inhibitor of Hedgehog (Hh) signaling; depletes stem-like cancer cells in glioblastoma|
|4027||16,16-Dimethyl Prostaglandin E2|
|Synthetic prostaglandin E2 (Cat. No. 2296) derivative; regulates HSC development|
|Cyclooxygenase inhibitor; regulates prostate stem cell antigen|
|GLI1 antagonist; inhibits Hh signaling|
|GLI antagonist; inhibits Hh signaling|
|Selective Hsp90 inhibitor; breast cancer stem cell inhibitor|
|Allosteric activator of Hedgehog signaling; induces Smo accumulation|
|PORCN inhibitor; suppresses self-renewal in R1 ESCs and promotes cardiomyocyte differentiation|
|Wnt/β-catenin signaling inhibitor; axin stabilizer|
|Downstream Hh signaling pathway inhibitor; inhibits alcohol dehydrogenase 7|
|Used for MEF/STO feeder layer preparation in stem cell culture|
|STAT3 inhibitor; blocks cancer stem cell self-renewal|
|STAT3 and mTORC1 signaling inhibitor; antineoplastic against AML stem cells|
|p53 inhibitor; supresses self renewal of embryonic stem cells|
|Major endogenous prostanoid|
|ARFGAP1 inhibitor; modulates Wnt signaling pathway|
|Mobilizes HSCs; high affinity fluorescent α4β1/α9β1 inhibitor|
|3667||SR 3677 dihydrochloride|
|Potent, selective Rho-kinase (ROCK) inhibitor|
|Tankyrase inhibitor; inhibits Wnt signaling|
|Tankyrase inhibitor; promotes cardiomyogenesis|
Stem cell generation, self-renewal and differentiation are controlled by various intra- and extracellular cues. In vivo, the microenvironment responsible for maintaining stem cells in pluripotent form and enabling their self-renewal is called the stem-cell niche. Environmental factors and certain signal pathways, such as the Wnt, JAK-STAT and TGF-β/BMP pathways, contribute to the maintenance of this niche.
Communication between the stem cells within this environment helps coordinate the process of differentiation, after it is triggered by signal molecules such as growth factors and Wnt proteins. Signaling pathways closely linked to developmental processes, and which are frequently dysregulated in cancer - e.g. Notch, Hedgehog and Wnt - have also been linked with the regulation of stem cell self-renewal. Internal signals, controlled by the cell's genes, play an equally important role in stem cell differentiation. While these signaling pathways are integral to the generation of specific differentiated cells, the mechanisms that determine differentiated cell type and destination are not entirely understood.
Figure 1: Schematic highlighting some of the key signaling pathways in stem cells. The proliferation and differentiation of stem cells are controlled by a network of signaling pathways. These pathways can be readily manipulated using small molecules (represented here in blue). Abbreviations: BMP, Bone morphogenetic protein; CK1, casein kinase 1; β-cat, β-catenin; DVL, Dishevelled; FGF, Fibroblast growth factor; FZD, Frizzled receptor; GSK, glycogen synthase kinase-3β; Hh, Hedgehog; NICD, Notch intracellular domain; PKA, protein kinase A; PORCN, Porcupine; PTCH, Patched receptor; SMO, Smoothened receptor; TGFβ, Transforming growth factor β.
Other signals result in the reprogramming of differentiated cells, generating embryonic stem-like cells. Transcription factors such as Oct4, Sox2 and Nanog regulate the expression of selected induction genes and are used to create pluripotent cells. These induced pluripotent stem cells (iPSCs) provide a viable alternative to embryonic stem cells (ESCs), without the moral issues affecting human ESC use. Recent research has moved away from the use of viruses and oncogenes to genetically alter adult cells; instead, recombinant proteins and chemicals have been used successfully to generate murine and human iPSCs (protein-induced pluripotent stem cells). The fusion of pluripotent cells with somatic cells also enables the transfer of pluripotent phenotype by an unknown mechanism.
Tocris offers the following scientific literature for Stem Cell Signaling to showcase our products. We invite you to request* or download your copy today!
*Please note that Tocris will only send literature to established scientific business / institute addresses.
Written by Kirsty E. Clarke, Victoria B. Christie, Andy Whiting and Stefan A. Przyborski, this review provides an overview of the use of small molecules in the control of stem cell growth and differentiation. Key signaling pathways are highlighted, and the regulation of ES cell self-renewal and somatic cell reprogramming is discussed. Compounds available from Tocris are listed.
Stem cells have potential as a source of cells and tissues for research and treatment of disease. This poster summarizes some key protocols demonstrating the use of small molecules across the stem cell workflow, from reprogramming, through self-renewal, storage and differentiation to verification. Advantages of using small molecules are also highlighted.