title: Integrated analysis of hematopoietic differentiation outcomes and molecular characterization reveals unbiased differentiation capacity and minor transcriptional memory in HPC/HSC-iPSCs.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  This work provides a comprehensive framework for obtaining high-quality iPSCs from HPC/HSCs with unbiased hematopoietic differentiation capacity and minor transcriptional memory.
authors.affiliation: School of Medicine, Shenzhen University, Nanhai Ave 3688, Shenzhen, 518060, Guangdong, China.|National Institute of Biological Sciences, NIBS, Beijing, 102206, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Gao
authors.affiliation: School of Medicine, Shenzhen University, Nanhai Ave 3688, Shenzhen, 518060, Guangdong, China.|National Institute of Biological Sciences, NIBS, Beijing, 102206, China.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Hou
authors.affiliation: National Institute of Biological Sciences, NIBS, Beijing, 102206, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: National Institute of Biological Sciences, NIBS, Beijing, 102206, China.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Xu
authors.affiliation: National Institute of Biological Sciences, NIBS, Beijing, 102206, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
authors.affiliation: School of Medicine, Shenzhen University, Nanhai Ave 3688, Shenzhen, 518060, Guangdong, China. chenjj@szu.edu.cn.
authors.forename: Jiajie
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Medicine, Shenzhen University, Nanhai Ave 3688, Shenzhen, 518060, Guangdong, China. changgang@szu.edu.cn.|National Institute of Biological Sciences, NIBS, Beijing, 102206, China. changgang@szu.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Chang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D018920:Coculture Techniques; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D012313:RNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D017423:Sequence Analysis, RNA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D014157:Transcription Factors; D012313:RNA
keywords: Differentiation; Hematopoietic progenitor and stem cells; Induced pluripotent stem cells; Transcriptional memory