Ultra-High-Frequency Reprogramming of Individual Long-Term Hematopoietic Stem Cells Yields Low Somatic Variant Induced Pluripotent Stem Cells

被引：10

作者：

Wang, Kai ^{[1
]}

Guzman, Anthony K. ^{[2
]}

Yan, Zi ^{[1
]}

Zhang, Shouping ^{[1
]}

Hu, Michael Y. ^{[1
]}

Hamaneh, Mehdi B. ^{[3
]}

Yu, Yi-Kuo ^{[3
]}

Tolu, Seda ^{[2
]}

Zhang, Jinghang ^{[4
]}

Kanavy, Holly E. ^{[2
]}

Ye, Kenny ^{[5
]}

Bartholdy, Boris ^{[1
]}

Bouhassira, Eric E. ^{[1
]}

机构：

[1] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10467 USA

[2] Albert Einstein Coll Med, Dept Internal Med, Div Dermatol, Bronx, NY 10467 USA

[3] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA

[4] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA

[5] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA

来源：

CELL REPORTS | 2019年 / 26卷 / 10期

关键词：

MUTATIONAL PROCESSES; CLONAL HEMATOPOIESIS; EMBRYONIC STEM; RATES; BLOOD; MOUSE; DIFFERENTIATION; QUANTIFICATION; SIGNATURES; INDUCTION;

D O I：

10.1016/j.celrep.2019.02.021

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Efficiency of reprogramming of human cells into induced pluripotent stem cells (iPSCs) has remained low. We report that individual adult human CD49f(+) long-term hematopoietic stem cells (LT-HSCs) can be reprogrammed into iPSCs at close to 50% efficiency using Sendai virus transduction. This exquisite sensitivity to reprogramming is specific to LT-HSCs, since it progressively decreases in committed progenitors. LT-HSC reprogramming can follow multiple paths and is most efficient when transduction is performed after the cells have exited G(0). Sequencing of 75 paired skin fibroblasts/LT-HSC samples collected from nine individuals revealed that LT-HSCs contain a lower load of somatic single-nucleotide variants (SNVs) and indels than skin fibroblasts and accumulate about 12 SNVs/year. Mutation analysis revealed that LT-HSCs and fibroblasts have very different somatic mutation signatures and that somatic mutations in iPSCs generally exist prior to reprogramming. LT-HSCs may become the preferred cell source for the production of clinical-grade iPSCs.

引用

页码：2580 / +

页数：20

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