Table 1.
Human stem cell models of Huntington’s disease and their phenotypes reported in the literature.
| Pluripotent Cell Type | CAG Repeat | Genetic Modification |
Differentiation Stage and Phenotypes | Reference |
|---|---|---|---|---|
| ESCs from HD embryos | 37 and 51 | no | Differentiated neurosphere cells showed expanded CAG repeat length instability |
11 |
| ESCs from HD embryos | 40, 45, 46 and 48 | no | No phenotype described | 12 |
| ESCs from HD embryos | 37 and 51 | no | CAG51 forebrain neurons had elevated glutamate-evoked responses such as intracellular calcium levels |
13 |
| H9 ESCs | 23, 73 and 145 |
HTT exonl under CAG promoter delivered by ePiggyBac system |
CAG73 and CAG145 neurons showed EM48 positive aggregates and increased cell death upon growth factor deprivation compared to CAG23 neurons |
14 |
| ESCs from HD embryos | 15/21, 18/21, 22/22, 12/40, 17/46, 17/48, 23/45, 19/41, 19/46,21/42 |
no | Proteomic analysis had mitochondria dysfunction in HD affected ESCs shown by reduction components of electron transport chain complex I, III and IV. Neurons from HD affected ESCs showed vulnerability to nonspecific kinase inhibitor STS. There were transcription dysregulation such as histone H1 family members and actin cytoskeletal signaling proteins in HD neurons |
10 |
| iPSCs from HD patient | 72 | no | No phenotype described | 31 |
| iPSCs from HD patient | 72 | no | Increased caspase activity upon growth factor deprivation in NSCs |
30 |
| iPSCs from HD patient | 50 and 109 | no | Increased cytoplasmic vacuolation seen in differentiated astrocytes |
29 |
| iPSCs from HD patient | 15/17, 15/18, 17/45,39/43,42/44 |
no | No difference in growth rate, differentiation, caspase activation in iPSCs. Higher lysosomal activity in HD-iPSCs and derived neurons shown by LysoTracker dye. Increased autophagesome formation in HD-iPSCs |
28 |
| iPSCs from HD patient | 72 | no | HD iPSCs form EM48+ aggregates upon treatment of proteasome inhibitor MG132. NPCs from HD iPSCs and developed EM48+ HD pathology characteristic at later stage of transplantation into rat quinolinic acid-induced HD model |
27 |
| iPSCs from HD patient | 72 | no | Dysregulated proteins involved in oxidative stress response, apoptosis in HD-iPSCs. Decreased neuronal differentiation and neurite outgrowth and increased apoptosis (TUNEL) in HD-iPSCs and neurons. Reduced cytoskeleton associated proteins in HD-neurons |
26 |
| iPSCs from HD patient | 72 | Expanded CAG was genetically corrected byHR |
At NSC stage, HD cells showed increased apoptosis (TUNEL), caspase activity, decreased BDNF expression, maximal oxygen consumption rate, altered TGF-β and cadherin signaling. Corrected NSCs reversed these DhenotvDes |
66 |
| iPSCs from HD patient | 17/21,21/28, 18/33, 18/60, 19/109, 18/180 |
no | Microarray analysis showed distinct gene expression pattern in differentiated NSCs. HD NSCs showed decrease in energy metabolism (lower intracellular ATP level and ATP/ADP ratio) and cell adhesion (smaller clump size). HD neurons had higher risk of cell death after prolonged culture (stained cleaved caspase-3), BDNF withdrawal (condensed nuclei and caspase activation) or stressed by H2O2 or 3-MA (condensed nuclei). Physiological or pathological glutamate treatment would increase percentage of HD neurons with calcium dyshomeostasis |
24 |
| iPSCs from HD patient | 72 | no | mHTT formed EM48 positive aggregates in differentiated neurons which could be reduced by microRNA miR-196a |
23 |
| iPSCs from HD patient (non-integrating method) |
18/21, 18/28,18/33, 18/60, 19/109, 18/180 |
no | More Nestin+ neural cells after differentiation of HD iPSCs. Withdrawal of BDNF caused more apoptosis (TUNEL) in HD neurons and reduced numbers of Nestin positive cells. |
36 |