Integrated analysis of hematopoietic differentiation outcomes and molecular characterization reveals unbiased differentiation capacity and minor transcriptional memory in HPC/HSC-iPSCs.
Stem Cell Res Ther, 2017/01/23;8(1):13.
Gao S[1, 2], Hou X[1, 2], Jiang Y[2], Xu Z[2], Cai T[2], Chen J[3], Chang G[4, 5]
Affiliations
PMID: 28114969DOI: 10.1186/s13287-016-0466-1
Impact factor: 8.079
Abstract
background: Transcription factor-mediated reprogramming can reset the epigenetics of somatic cells into a pluripotency compatible state. Recent studies show that induced pluripotent stem cells (iPSCs) always inherit starting cell-specific characteristics, called epigenetic memory, which may be advantageous, as directed differentiation into specific cell types is still challenging; however, it also may be unpredictable when uncontrollable differentiation occurs. In consideration of biosafety in disease modeling and personalized medicine, the availability of high-quality iPSCs which lack a biased differentiation capacity and somatic memory could be indispensable.
methods: Herein, we evaluate the hematopoietic differentiation capacity and somatic memory state of hematopoietic progenitor and stem cell (HPC/HSC)-derived-iPSCs (HPC/HSC-iPSCs) using a previously established sequential reprogramming system.
results: We found that HPC/HSCs are amenable to being reprogrammed into iPSCs with unbiased differentiation capacity to hematopoietic progenitors and mature hematopoietic cells. Genome-wide analyses revealed that no global epigenetic memory was detectable in HPC/HSC-iPSCs, but only a minor transcriptional memory of HPC/HSCs existed in a specific tetraploid complementation (4 N)-incompetent HPC/HSC-iPSC line. However, the observed minor transcriptional memory had no influence on the hematopoietic differentiation capacity, indicating the reprogramming of the HPC/HSCs was nearly complete. Further analysis revealed the correlation of minor transcriptional memory with the aberrant distribution of H3K27me3.
conclusions: This work provides a comprehensive framework for obtaining high-quality iPSCs from HPC/HSCs with unbiased hematopoietic differentiation capacity and minor transcriptional memory.
Keywords: Differentiation; Hematopoietic progenitor and stem cells; Induced pluripotent stem cells; Transcriptional memory
MeSH terms
Animals; Cell Differentiation; Cellular Reprogramming; Coculture Techniques; DNA Methylation; Epigenesis, Genetic; Hematopoietic Stem Cells; Histones; Induced Pluripotent Stem Cells; Mice; RNA; Sequence Analysis, RNA; Transcription Factors; Transcription, Genetic
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