SK-N-SH (ATCC HTB-11) is a human neuroblastoma cell line widely used in neurobiology and neurodegeneration research. Established from a bone marrow metastasis in a 4-year-old female patient in 1970, this cell line serves as a valuable in vitro model for studying neuronal differentiation, neurotoxicity, and therapeutic interventions for neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD)[1][2].
The cell line exhibits a unique bipotential nature, with cells capable of existing in either a neuronal (N-type) or substrate-adherent (S-type) morphology. This heterogeneity reflects the developmental plasticity of neural crest-derived cells and has made SK-N-SH a valuable model for studying cellular differentiation and lineage commitment[3].
| Property | Value |
|---|---|
| Organism | Homo sapiens (human) |
| Age | 4 years |
| Gender | Female |
| Disease | Neuroblastoma |
| Tissue | Brain |
| Metastatic site | Bone marrow |
| Growth properties | Adherent |
| Morphology | Epithelial (S-type) / Neuronal (N-type) |
| Karyotype | Hyperdiploid human female (XX), modal chromosome number 47, trisomic for N7 |
| Biosafety Level | BSL 1 |
| Medium | Eagle's Minimum Essential Medium (EMEM) + 10% FBS |
| Temperature | 37°C |
| Doubling time | ~48 hours |
The SK-N-SH cell line was developed by J.L. Biedler and colleagues at the Memorial Sloan Kettering Cancer Center[1:1]. The cell line was deposited by G. Trempe and L.J. Old and accessioned into the ATCC collection as HTB-11.
SK-N-SH differs from related neuroblastoma lines (such as SK-N-MC, ATCC HTB-10) in several key aspects:
The cell line represents a committed neuronal lineage derived from the neural crest, explaining its ability to produce neurotransmitters and express neuronal markers[2:1][3:1].
SK-N-SH cells exist in two main morphological forms:
N-type (neuronal) cells:
S-type (substrate-adherent) cells:
The ratio of N-type to S-type cells can be modulated by culture conditions and differentiation agents[3:2].
Key neuronal markers expressed in SK-N-SH include:
Cytoskeletal proteins:
Enzymes and metabolic markers:
Synaptic markers:
Surface receptors:
SK-N-SH cells possess functional neurotransmitter systems:
Dopaminergic properties:
GABAergic properties:
Cholinergic properties:
SK-N-SH cells can be differentiated toward a more mature neuronal phenotype using various agents. Differentiated cells show enhanced neuronal characteristics and are more relevant for studying age-related neurodegeneration[5].
All-trans retinoic acid (RA) is the most commonly used differentiation agent:
Protocol:
Results:
Mechanism: RA acts through nuclear retinoic acid receptors (RARs) to regulate gene expression programs involved in neuronal differentiation.
Brain-derived neurotrophic factor promotes neuronal differentiation and survival:
Protocol:
Results:
A two-stage protocol produces more mature neurons:
Stage 1 (Days 1-5):
Stage 2 (Days 6-10):
This protocol yields cells with more elaborate neurite networks and higher expression of synaptic markers[6:2].
Elevated intracellular cAMP drives neuronal differentiation:
Protocol:
Results:
Phorbol 12-myristate 13-acetate (PMA) activates PKC:
Protocol:
Results:
SK-N-SH cells have been extensively used as an in vitro model for studying Alzheimer's disease mechanisms[8]:
SK-N-SH express Trk receptors and are used to study:
Pharmaceutical and academic researchers use SK-N-SH for:
SK-N-SH cells serve as a valuable model for PD research, particularly for dopaminergic neuron biology[10]:
SK-N-SH can be differentiated toward a dopaminergic phenotype:
The cell line is used to model Lewy body pathology:
PD-relevant neurotoxins are used to model dopaminergic degeneration:
MPP+ (1-methyl-4-phenylpyridinium):
6-Hydroxydopamine (6-OHDA):
Rotenone:
SK-N-SH expressing mutant LRRK2 are used to study:
SK-N-SH cells are readily amenable to genetic manipulation:
| Cell Line | ATCC | Characteristics |
|---|---|---|
| SH-SY5Y | CRL-2266 | Differentiated subclone of SK-N-SH, more homogeneous, widely used in PD research |
| SK-N-MC | HTB-10 | Related neuroblastoma, shorter doubling time |
| IMR-32 | CCL-127 | Another human neuroblastoma line, different morphology |
| M17 | — | Human neuroblastoma with dopaminergic characteristics |
| LUHMES | — | Conditionally immortalized human neuronal precursor |
| PC12 | CRL-1721 | Rat pheochromocytoma, neuronal model |
Despite these limitations, SK-N-SH remains a valuable and widely-used model system for initial studies and drug screening before validation in more complex systems.
Biedler JL, Helson L, Spengler BA. Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture. Cancer Research. 1973. ↩︎ ↩︎
Ciccarone V, Spengler BA, Meyers MB, Biedler JL. Phenotypic diversification in human neuroblastoma cells: expression of distinct neural crest lineages. Cancer Research. 1989. ↩︎ ↩︎
Ross RA, Spengler BA, Biedler JL. Coordinate morphological and biochemical interconversion of human neuroblastoma cells. Journal of the National Cancer Institute. 1983. ↩︎ ↩︎ ↩︎
Cheng B, Narang A, Liao H, Barger SW. Dopamine metabolism and oxidative stress in cultured neuronal cells. Brain Research. 2002. ↩︎ ↩︎
Påhlman S, Ruusala AI, Abrahamsson L, Mattsson ME, Esscher T. Retinoic acid-induced differentiation of human neuroblastoma cells: a cell model system for study of neuronal cell differentiation. Biomedicine & Pharmacotherapy. 1991. ↩︎ ↩︎
Encinas M, Iglesias M, Liu Y, et al. Sequential treatment of SH-SY5Y cells with retinoic acid and brain-derived neurotrophic factor gives rise to fully differentiated, neurotrophic factor-dependent, human neuron-like cells. Journal of Neurochemistry. 2000. ↩︎ ↩︎ ↩︎
Scheibe RJ, Ginty DD, Hueber LG. The effect of forskolin on differentiation of the human neuroblastoma cell line SK-N-SH. Developmental Biology. 1986. ↩︎
Yao J, Du R, Wang T, et al. Amyloid beta-induced neuronal apoptosis is associated with mitochondrial dysfunction and cytochrome c release. Neurochemical Research. 2011. ↩︎ ↩︎
Chen Y, Liang Z, Blanchard J, et al. A non-transgenic mouse model of tauopathy induced by okadaic acid. Journal of Alzheimer's Disease. 2013. ↩︎ ↩︎
Xie HR, Hu LS, Li GY. SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson's disease. Chinese Medical Journal. 2010. ↩︎ ↩︎
da Silva JD, Lopes MH. Alpha-synuclein biology in cellular models of Parkinson's disease. Journal of Neural Transmission. 2022. ↩︎
Cookson MR. The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease. Nature Reviews Neuroscience. 2010. ↩︎