2014
DOI: 10.1038/ncomms6605
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Somatic transcriptome priming gates lineage-specific differentiation potential of human-induced pluripotent stem cell states

Abstract: Human-induced pluripotent stem cells (hiPSCs) provide an invaluable source for regenerative medicine, but are limited by proficient lineage-specific differentiation. Here we reveal that hiPSCs derived from human fibroblasts (Fibs) versus human cord blood (CB) exhibit indistinguishable pluripotency, but harbour biased propensities for differentiation. Genes associated with germ layer specification were identical in Fib-or CB-derived iPSCs, whereas lineage-specific marks emerge upon differentiation induction of … Show more

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Cited by 45 publications
(40 citation statements)
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“…Compared with fibroblasts from skin biopsy, the un-invasive urine cells as reprogramming parental cell is much more acceptable. It has previously been reported that human iPSCs derived from different cellular origins (fibroblasts versus cord blood) showed indistinguishable pluripotency, but haboured biased tendency for lineage-specific differentiation [25]. However, the present study revealed that there were no significant differences in the specification and maturation of motor neurons between fibroblasts and urine cells derived SMA iPSCs.…”
Section: Discussioncontrasting
confidence: 66%
“…Compared with fibroblasts from skin biopsy, the un-invasive urine cells as reprogramming parental cell is much more acceptable. It has previously been reported that human iPSCs derived from different cellular origins (fibroblasts versus cord blood) showed indistinguishable pluripotency, but haboured biased tendency for lineage-specific differentiation [25]. However, the present study revealed that there were no significant differences in the specification and maturation of motor neurons between fibroblasts and urine cells derived SMA iPSCs.…”
Section: Discussioncontrasting
confidence: 66%
“…Human iPSC cultures often represent a progenitor stage and fail to complete differentiation to HSCs in vivo [11]. Furthermore, fibroblast-derived iPSCs exhibit a lower hematopoietic differentiation efficiency than cord blood-derived-iPSCs, which is due to lineage memory issues [25,26]. Here, we found that MEFderived iPSCs had the same differentiation potential as ESCs for multiple lymphocyte lineages without any bias compared with WT controls.…”
Section: Discussionmentioning
confidence: 50%
“…Additionally, epigenetic memory renders iPSCs prone to differentiate to their original somatic cell lineage [23,24]. Similarly, cord blood-derived iPSCs possess an enhanced hematopoietic differentiation potential compared with fibroblast-derived iPSCs [25,26]. Furthermore, iPSCs show a limited differentiation capacity for certain lineages such as hematopoietic cells, hepatocytes, and pancreatic cells [17,20,27,28].…”
Section: Introductionmentioning
confidence: 99%
“…A recent study identified a panel of 82 CpG methylation sites that could distinguish poor-quality hiPSCs from hESCs with high accuracy [96]. In accordance, a clear somatic memory was observed showing that lineage-specific marks emerge upon differentiation induction of hiPSCs that correlate to the cell of origin [97]. However, paralleling studies using the mouse system, different studies found comparable frequencies of coding mutations and loss of imprinting in human pluripotent cells derived by either nuclear transfer or defined factors introduced by non-integrating agents [98].…”
Section: Lessons Learned From Human Cellsmentioning
confidence: 65%