Stem Cell Signaling

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.

Products
Background
Literature (4)
Pathways (3)
Cat. No. Product Name / Activity
1515 17-AAG
Selective Hsp90 inhibitor; protects neuroprogenitor cells against stress-induced apoptosis
3979 Alexidine dihydrochloride
Selective inhibitor of PTPMT1; maintains functional HSCs ex vivo
3299 AMD 3100 octahydrochloride
Highly selective CXCR4 antagonist; mobilizes hematopoietic stem cells in vivo
3194 BIO
Maintains self-renewal and pluripotency of ESCs; potent inhibitor of GSK-3; also inhibits cdks
5051 BIO 5192
Integrin α4β1 inhibitor; mobilizes HSCs and progenitors
3874 BIO-acetoxime
Selective GSK-3α/β inhibitor; inhibits CD8+ T cell effector differentiation
6047 BOP
Preferentially mobilizes HSCs; dual α9β1/α4β1 integrin inhibitor
5050 CASIN
Cdc42 GTPase inhibitor; functionally rejuvenates aged HSCs
4529 Ciliobrevin A
Hedgehog pathway antagonist; inhibits ciliogenesis
1623 Cyclopamine
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
1769 Flurbiprofen
Cyclooxygenase inhibitor; regulates prostate stem cell antigen
3889 GANT 58
GLI1 antagonist; inhibits Hh signaling
3191 GANT 61
GLI antagonist; inhibits Hh signaling
1368 Geldanamycin
Selective Hsp90 inhibitor; breast cancer stem cell inhibitor
4474 20(S)-Hydroxycholesterol
Allosteric activator of Hedgehog signaling; induces Smo accumulation
3533 IWP 2
PORCN inhibitor; suppresses self-renewal in R1 ESCs and promotes cardiomyocyte differentiation
3532 endo-IWR 1
Wnt/β-catenin signaling inhibitor; axin stabilizer
3341 JK 184
Downstream Hh signaling pathway inhibitor; inhibits alcohol dehydrogenase 7
3603 Kaempferol
TAZ activator; promotes osteogenesis from MSCs; also activates mitochondrial Ca2+ uniporter
3258 Mitomycin C
Used for MEF/STO feeder layer preparation in stem cell culture
5522 Napabucasin
STAT3 inhibitor; blocks cancer stem cell self-renewal
4079 Niclosamide
STAT3 and mTORC1 signaling inhibitor; antineoplastic against AML stem cells
1267 Pifithrin-α hydrobromide
p53 inhibitor; supresses self renewal of embryonic stem cells
2296 Prostaglandin E2
Major endogenous prostanoid
3324 QS 11
ARFGAP1 inhibitor; modulates Wnt signaling pathway
6048 R-BC154
Mobilizes HSCs; high affinity fluorescent α4β1/α9β1 inhibitor
3667 SR 3677 dihydrochloride
Potent, selective Rho-kinase (ROCK) inhibitor
4855 WIKI4
Tankyrase inhibitor; inhibits Wnt signaling
3748 XAV 939
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.


Key Stem Cell Signaling Pathways

Key signaling pathways in stem cells

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.

Literature for Stem Cell Signaling

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.


Stem Cell

Stem Cell Research Product Guide

This product guide provides a background to the use of small molecules in stem cell research and lists over 200 products for use in:

  • Self-renewal and Maintenance
  • Differentiation
  • Reprogramming
  • Organoid Generation
  • Regenerative Medicine
Stem Cells

Stem Cells Scientific Review

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 Cell Workflow

Stem Cell Workflow Poster

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.

Stem Cells

Stem Cells Poster

Written by Rebecca Quelch and Stefan Przyborski from Durham University (UK), this poster describes the isolation of pluripotent stem cells, their maintenance in culture, differentiation, and the generation and potential uses of organoids.

Pathways for Stem Cell Signaling

Notch

Notch Signaling Pathway

The Notch pathway is involved in determination of cell fate, regulation of pattern formation and other developmental settings. Disrupted signaling can cause developmental defects and a range of adult pathologies.
TGF-β

TGF-β Signaling Pathway

The TGF-β signaling pathway is involved in the regulation of growth and proliferation of cells along with migration, differentiation and apoptosis.
Wnt

Wnt Signaling Pathway

The Wnt pathway is involved in cellular differentiation and proliferation in adult tissues and also during embryogenesis. Disturbances within the pathway may lead to the formation of tumors and promote metastasis.