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

Summary: 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 Dishwasher Basket Stopper Pin 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 TRANQUIL SLEEP EXTRA STRENGTH 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.: Wang et al.

show that single adult human long-term hematopoietic stem cells can be reprogrammed into induced pluripotent stem cells at close to 50% efficiency and contain fewer somatic single-nucleotide variants and indels than skin fibroblasts.They may become the preferred source for the production of clinical-grade iPSCs.Keywords: long-term hematopoietic stem cells, reprogramming, induced pluripotent stem cells, skin fibroblasts, somatic mutation.

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