Generation of integration-free Down syndrome and isogenic euploid human induced pluripotent stem cells.

A pair of Down syndrome (DS) human iPSCs (hiPSCs) and isogenic euploid hiPSCs generated by using an integration-free Sendai viral vector system showed trisomy 21 (47; XY) and typical (46; XY) karyotype respectively. Pluripotency of both hiPSC lines was confirmed by pluripotency marker expression and three germ layer differentiation potentials.

Biphasic cell cycle defect causes impaired neurogenesis in down syndrome.

Impaired neurogenesis in Down syndrome (DS) is characterized by reduced neurons, increased glial cells, and delayed cortical lamination. However, the underlying cause for impaired neurogenesis in DS is not clear. Using both human and mouse iPSCs, we demonstrate that DS impaired neurogenesis is due to biphasic cell cycle dysregulation during the generation of neural progenitors from iPSCs named the "neurogenic stage" of neurogenesis.

Generation of AAVS1-EGFP reporter cell lines from an isogenic pair of trisomy 21 and euploid human iPSCs.

Human mouse chimeric models are valuable tools to develop in-vivo disease models. However, in-vivo detection of human cells limits their analysis. To facilitate in-vivo modeling of Down syndrome (DS), we generated a stable AAVS1-EGFP isogenic pair of DS human iPSCs by zinc finger mediated genetic engineering of the AAVS1 locus.

Generation of integration free hiPSCs clones, NSi001-A, NSi001-B, and NSi001-C from peripheral blood mononuclear cells of an individual with down syndrome having Robertsonian translocation.

Human-induced pluripotent stem cells (hiPSCs) clones NSi001-A, NSi001-B, and NSi001-C were generated from a female individual of Indian origin having Robertsonian translocation down syndrome (DS) by reprogramming peripheral blood mononuclear cells (PBMCs) using integration-free Sendai viral vectors. The established hiPSCs clones had karyotype similar to the patient sample with Robertsonian translocation [46, XX rob (14;21)], normal ES-like morphology, expression of pluripotency markers, and potential for three germ layer differentiation, i.e.