Analysis of genotype effects and inter-individual variability in iPSC-derived trisomy 21 neural progenitor cells

生物 诱导多能干细胞 转录组 祖细胞 非整倍体 遗传学 神经干细胞 表型 细胞生物学 干细胞 胚胎干细胞 基因表达 基因 染色体
作者
Sarah E. Lee,Laura L. Baxter,Manuel Durán,Sidney M. Morris,Iman A Mosley,K. Fuentes,Jeroen L. A. Pennings,Fayçal Guedj,Diana W. Bianchi
出处
期刊:Human Molecular Genetics [Oxford University Press]
标识
DOI:10.1093/hmg/ddae160
摘要

Abstract Trisomy of human chromosome 21 (T21) gives rise to Down syndrome (DS), the most frequent live-born autosomal aneuploidy. T21 triggers genome-wide transcriptomic alterations that result in multiple atypical phenotypes with highly variable penetrance and expressivity in individuals with DS. Many of these phenotypes, including atypical neurodevelopment, emerge prenatally. To enable in vitro analyses of the cellular and molecular mechanisms leading to the neurological alterations associated with T21, we created and characterized a panel of genomically diverse T21 and euploid induced pluripotent stem cells (iPSCs). We subsequently differentiated these iPSCs to generate a panel of neural progenitor cells (NPCs). Alongside characterizing genotype effects from T21, we found that T21 NPCs showed inter-individual variability in growth rates, oxidative stress, senescence characteristics, and gene and protein expression. Pathway enrichment analyses of T21 NPCs identified vesicular transport, DNA repair, and cellular response to stress pathways. These results demonstrate T21-associated variability at the cellular level and suggest that cell lines from individuals with DS should not solely be analyzed as a homogenous population. Examining large cohorts of genetically diverse samples may more fully reveal the effects of aneuploidy on transcriptomic and phenotypic characteristics in T21 cell types. A panel of genomically diverse T21 and euploid induced pluripotent stem cells (iPSCs) were created and subsequently differentiated into neural progenitor cells (NPCs). T21 NPCs showed reduced growth, increased oxidative stress, and inter-individual variability in gene and protein expression. This inter-individual variability suggests that studies with large cohorts of genetically diverse T21 samples may more fully reveal the effects of aneuploidy.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
3w学术完成签到 ,获得积分10
1秒前
量子星尘发布了新的文献求助10
1秒前
XU博士完成签到,获得积分10
2秒前
万能图书馆应助cata采纳,获得10
2秒前
Dr大壮完成签到,获得积分10
4秒前
猪猪女孩完成签到,获得积分10
5秒前
livra1058完成签到,获得积分10
5秒前
大可完成签到 ,获得积分10
6秒前
Orochimaru完成签到,获得积分10
8秒前
小神仙完成签到 ,获得积分10
8秒前
星辰大海应助Much采纳,获得100
10秒前
abtitw完成签到,获得积分10
11秒前
青黛完成签到 ,获得积分10
14秒前
传统的松鼠完成签到 ,获得积分10
16秒前
量子星尘发布了新的文献求助10
17秒前
19秒前
cata完成签到,获得积分10
19秒前
TGU的小马同学完成签到 ,获得积分10
20秒前
my完成签到,获得积分10
21秒前
jlux完成签到,获得积分10
22秒前
ioio完成签到 ,获得积分10
23秒前
everyone_woo完成签到,获得积分10
23秒前
wxiao完成签到,获得积分10
25秒前
25秒前
Hello应助jlux采纳,获得10
25秒前
影月完成签到,获得积分10
27秒前
jeffrey完成签到,获得积分0
27秒前
机灵的丹寒完成签到 ,获得积分10
28秒前
29秒前
zhangxinan完成签到,获得积分10
30秒前
余生完成签到 ,获得积分10
30秒前
诚心的人雄应助岩崖采纳,获得10
32秒前
32秒前
江雁完成签到,获得积分10
32秒前
佰斯特威完成签到,获得积分10
36秒前
奈何桥完成签到,获得积分10
36秒前
梦璃完成签到 ,获得积分10
37秒前
量子星尘发布了新的文献求助10
37秒前
Ttimer完成签到,获得积分10
38秒前
40秒前
高分求助中
International Code of Nomenclature for algae, fungi, and plants (Madrid Code) (Regnum Vegetabile) 1500
Functional High Entropy Alloys and Compounds 1000
Building Quantum Computers 1000
Molecular Cloning: A Laboratory Manual (Fourth Edition) 500
Social Epistemology: The Niches for Knowledge and Ignorance 500
优秀运动员运动寿命的人文社会学因素研究 500
Principles of Plasma Discharges and Materials Processing,3rd Edition 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4236520
求助须知:如何正确求助?哪些是违规求助? 3770183
关于积分的说明 11841026
捐赠科研通 3426808
什么是DOI,文献DOI怎么找? 1880714
邀请新用户注册赠送积分活动 933251
科研通“疑难数据库(出版商)”最低求助积分说明 840148