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Cell Rep. 2019 Mar 5;26(10):2580-2592.e7. doi: 10.1016/j.celrep.2019.02.021.

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

Author information

1
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY.
2
Department of Internal Medicine, Division of Dermatology, Albert Einstein College of Medicine, Bronx, NY.
3
National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD.
4
Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY.
5
Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY.
6
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY. Electronic address: eric.bouhassira@einstein.yu.edu.

Abstract

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 G0. 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.

KEYWORDS:

induced pluripotent stem cells; long-term hematopoietic stem cells; reprogramming; skin fibroblasts; somatic mutation

PMID:
30840883
DOI:
10.1016/j.celrep.2019.02.021
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