scholarly journals Trisomy Correction in Down Syndrome Induced Pluripotent Stem Cells

2012 ◽  
Vol 11 (5) ◽  
pp. 615-619 ◽  
Author(s):  
Li B. Li ◽  
Kai-Hsin Chang ◽  
Pei-Rong Wang ◽  
Roli K. Hirata ◽  
Thalia Papayannopoulou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Down Syndrome ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent

scholarly journals Generation of disease-specific induced pluripotent stem cells from patients with different karyotypes of Down syndrome

2012 ◽  
Vol 3 (2) ◽  
pp. 14 ◽  
Author(s):  
Xiaoning Mou ◽  
Yuanbo Wu ◽  
Henghua Cao ◽  
Qingzhang Meng ◽  
Qihui Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Down Syndrome ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent ◽  
Disease Specific

scholarly journals Generation of Integration-Free Induced Pluripotent Stem Cells from Urine-Derived Cells Isolated from Individuals with Down Syndrome

2017 ◽  
Vol 6 (6) ◽  
pp. 1465-1476 ◽  
Author(s):  
Young M. Lee ◽  
Bruna L. Zampieri ◽  
Jonah J. Scott-McKean ◽  
Mark W. Johnson ◽  
Alberto C.S. Costa
Keyword(s):  
Stem Cells ◽  
Down Syndrome ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent

Abstract P515: Dynamics Of Cardiomyocyte Differentiation In Isogenic Induced Pluripotent Stem Cells Derived From Trisomy21 Patients Hints Molecular Pathology Of Congenital Heart Defects In Down Syndrome

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Malay Chaklader ◽  
Beverly A Rothermel
Keyword(s):  
Stem Cells ◽  
Down Syndrome ◽  
Induced Pluripotent Stem Cells ◽  
Congenital Heart Defects ◽  
Pluripotent Stem Cells ◽  
Congenital Heart ◽  
Heart Defects ◽  
Congenital Defects ◽  
Cardiac Progenitors ◽  
Induced Pluripotent

Down syndrome (DS) is the most frequently occurring human chromosomal disorder and is responsible for a range of both congenital defects and progressive, degenerative conditions. For instance, an estimated 50% DS neonates are born with congenital heart defects (CHD) and more than 50% of DS adults develop early onset Alzheimer’s. Using induced pluripotent stem cells (iPSCs) derived from DS patients and isogenic controls we previously demonstrated the presence of a hyper-metabolic, hyper-fused mitochondrial network in trisomic iPSCs (3S-iPSCs) compared to disomic (2S-iPSCs) controls. Furthermore, mitochondrial function was normalized by siRNA depletion of RCAN1, an inhibitor of the protein phosphatase calcineurin (CN). Both CN signaling and mitochondrial metabolism have been implicated in a variety of steps during the progression from embryonic stem cells to cardiac progenitors, including self-renewal, exit from pluripotency, and commitment to cardiac verses hematopoietic lineages. Based on this, we hypothesized that the dynamics of many of these processes will be altered over the course of differentiation of 3S-iPSCs to cardiomyocytes when compared to 2S-iPSCs. Here, we investigate the temporal expression of pluripotency associated genes and lineage associated genes as well as cardiac mesoderm and mature cardiomyocyte specific genes. We also define and compare changes in CN activity, expression of specific CN isoforms, mitochondrial expansion, ROS generation, and activation of stress responses. Our study identifies early developmental and metabolic sequelae capable of contributing to CHD in DS that may result from a disruption in the normal balance in crosstalk between CN and RCAN1.

Integration-Free Induced Pluripotent Stem Cells Model Genetic and Neural Developmental Features of Down Syndrome Etiology

Stem Cells ◽  
2013 ◽  
Vol 31 (3) ◽  
pp. 467-478 ◽  
Author(s):  
James A. Briggs ◽  
Jane Sun ◽  
Jill Shepherd ◽  
Dmitry A. Ovchinnikov ◽  
Tung-Liang Chung ◽  
...  
Keyword(s):  
Stem Cells ◽  
Down Syndrome ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent ◽  
Developmental Features

Hematopoiesis of Human Induced Pluripotent Stem Cells Derived From Patients with Down Syndrome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 881-881
Author(s):  
Natsumi Nishihama ◽  
Yasuhiro Ebihara ◽  
Feng Ma ◽  
Wenyu Yang ◽  
Daisuke Tomizawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Down Syndrome ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Colony Formation ◽  
Trisomy 21 ◽  
Conflicts Of Interest ◽  
P Value ◽  
Increased Risk ◽  
Induced Pluripotent

Abstract Abstract 881 Trisomy 21, genetic hallmark of Down syndrome, is the most frequent human chromosomal abnormality. Infants and children with Down Syndrome (DS) are known to have some hematological disorders with an increased risk of developing leukemia. Ten to 20% of newborn with DS are diagnosed as neonatal preleukemic status, Transient Myeloproliferative Disorder (TMD), and approximately 30% of TMD patients are predisposed to acute megakaryoblastic leukemia (AMKL). Recently, acquired mutations in the N-terminal activation domain of the GATA1 gene, leading to expression of a shorter GATA1 isoform (GATA1s), have been reported in AMKL and TMD (Wechsler et al., 2002; Mundschau et al., 2003), but neither patients nor mice with germline mutations leading to expression of GATA1s developed AMKL and TMD in the absent of trisomy 21. These findings suggested that trisomy 21 itself directly contributes to the development of AMKL and TMD. However, the role of trisomy 21 in hematopoiesis, particularly in the human fetus remains poorly understood. To better understand the effects of trisomy 21 on hematopoiesis in embryonic stage and leukemogenesis, we employed human induced pluripotent stem cells (hiPSCs) derived from patients with DS (DS-hiPSCs). Six DS-hiPS and 5 hiPS cell lines (control) from healthy donors, which we used here, were all created from skin fibroblasts and reprogrammed by the defined 3 or 4 reprogramming factors (OCT3/4, KLF4, and SOX2, or c-MYC in addition to the 3 factors, respectively). We generated blood cells from DS-hiPSCs and controls with coculture system using murine aorta-gonad-mesonephros (AGM)-derived stromal cell line (Ma et al., 2009). The cells from hiPSCs were harvested at D11 or D12 of coculture and analyzed the presence of hematopoietic markers and the potentials of hematopoietic colony formation. In the experiments using hiPSCs reprogrammed by 3 factors, human CD34 expression in harvested cells from DS-hiPSCs or controls were detected 10.06 ± 4.35% and 3.04%, respectively. CD45 expression of CD34+ cells was small proportion in both DS-hiPSCs and controls. We next examined the hematopoietic colony formation. Both myeloid and erythroid colonies were detected. Number of colonies formed from DS-hiPSCs was 43.7±11.1 to 74.3±11.2 per an iPSC colony. It's approximately 2 to 3.5 folds numbers of control (p-value<0.05). Similar results were obtained in the experiments using hiPSCs reprogrammed by 4 factors. These results indicated that hiPSCs derived from patients with Down syndrome could differentiate into multiple hematopoietic cell lineages and the differentiation into hematopoietic lineage was promoted in DS patients. Further researches are under investigation to identify the responsible genes in trisomy 21 for acceleration of hematopoiesis with microarray analysis. Our study may contribute to understanding of the effects of trisomy 21 on hematopoiesis and effective use of patients derived hiPSCs in research and clinical application. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document