PMID- 35249258
OWN - NLM
STAT- MEDLINE
DCOM- 20220412
LR  - 20220511
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 26
IP  - 8
DP  - 2022 Apr
TI  - Analyses of erythropoiesis from embryonic stem cell-CD34(+) and cord 
      blood-CD34(+) cells reveal mechanisms for defective expansion and enucleation of 
      embryomic stem cell-erythroid cells.
PG  - 2404-2416
LID - 10.1111/jcmm.17263 [doi]
AB  - Red blood cells (RBCs) generated ex vivo have the potential to be used for 
      transfusion. Human embryonic stem cells (ES) and induced pluripotent stem cells 
      (iPS) possess unlimited self-renewal capacity and are the preferred cell sources 
      to be used for ex vivo RBC generation. However, their applications are hindered 
      by the facts that the expansion of ES/iPS-derived erythroid cells is limited and 
      the enucleation of ES/iPS-derived erythroblasts is low compared to that derived 
      from cord blood (CB) or peripheral blood (PB). To address this, we sought to 
      investigate the underlying mechanisms by comparing the in vitro erythropoiesis 
      profiles of CB CD34(+) and ES CD34(+) cells. We found that the limited expansion 
      of ES CD34(+) cell-derived erythroid cells was associated with defective cell 
      cycle of erythroid progenitors. In exploring the cellular and molecular 
      mechanisms for the impaired enucleation of ES CD34(+) cell-derived orthochromatic 
      erythroblasts (ES-ortho), we found the chromatin of ES-ortho was less condensed 
      than that of CB CD34(+) cell-derived orthochromatic erythroblasts (CB-ortho). At 
      the molecular level, both RNA-seq and ATAC-seq analyses revealed that pathways 
      involved in chromatin modification were down-regulated in ES-ortho. Additionally, 
      the expression levels of molecules known to play important role in chromatin 
      condensation or/and enucleation were significantly lower in ES-ortho compared to 
      that in CB-ortho. Together, our findings have uncovered mechanisms for the 
      limited expansion and impaired enucleation of ES CD34(+) cell-derived erythroid 
      cells and may help to improve ex vivo RBC production from stem cells.
CI  - (c) 2022 The Authors. Journal of Cellular and Molecular Medicine published by 
      Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
FAU - Wang, Shihui
AU  - Wang S
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou, China.
AD  - Laboratory of Membrane Biology, New York Blood Center, New York, New York, USA.
FAU - Zhao, Huizhi
AU  - Zhao H
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou, China.
FAU - Zhang, Huan
AU  - Zhang H
AD  - Laboratory of Membrane Biology, New York Blood Center, New York, New York, USA.
FAU - Gao, Chengjie
AU  - Gao C
AD  - Laboratory of Membrane Biology, New York Blood Center, New York, New York, USA.
FAU - Guo, Xinhua
AU  - Guo X
AD  - Laboratory of Membrane Biology, New York Blood Center, New York, New York, USA.
FAU - Chen, Lixiang
AU  - Chen L
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou, China.
FAU - Lobo, Cheryl
AU  - Lobo C
AD  - Laboratory of Blood Borne Parasites, New York Blood Center, New York, New York, 
      USA.
FAU - Yazdanbakhsh, Karina
AU  - Yazdanbakhsh K
AD  - Laboratory of Complement Biology, New York Blood Center, New York, New York, USA.
FAU - Zhang, Shijie
AU  - Zhang S
AD  - School of Life Sciences, Zhengzhou University, Zhengzhou, China.
FAU - An, Xiuli
AU  - An X
AD  - Laboratory of Membrane Biology, New York Blood Center, New York, New York, USA.
LA  - eng
GR  - R01 HL140625/HL/NHLBI NIH HHS/United States
GR  - 81870094/National Natural Science Foundation of China/
GR  - U1804282/National Natural Science Foundation of China/
GR  - 81700102/National Natural Science Foundation of China/
GR  - 81870095/National Natural Science Foundation of China/
GR  - P01 HL149626/HL/NHLBI NIH HHS/United States
GR  - 202102310040/Science and Technology Research Project of Henan/
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220305
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Antigens, CD34)
RN  - 0 (Chromatin)
SB  - IM
MH  - Antigens, CD34/metabolism
MH  - Cell Differentiation
MH  - Chromatin/metabolism
MH  - Embryonic Stem Cells/metabolism
MH  - Erythroid Cells
MH  - *Erythropoiesis
MH  - *Fetal Blood
MH  - Humans
PMC - PMC8995447
OTO - NOTNLM
OT  - ATAC-Seq
OT  - RNA-Seq
OT  - enucleation
OT  - erythropoiesis
COIS- The authors declare no competing financial interests.
EDAT- 2022/03/07 06:00
MHDA- 2022/04/13 06:00
PMCR- 2022/04/01
CRDT- 2022/03/06 20:38
PHST- 2022/02/21 00:00 [revised]
PHST- 2021/08/11 00:00 [received]
PHST- 2022/02/24 00:00 [accepted]
PHST- 2022/03/07 06:00 [pubmed]
PHST- 2022/04/13 06:00 [medline]
PHST- 2022/03/06 20:38 [entrez]
PHST- 2022/04/01 00:00 [pmc-release]
AID - JCMM17263 [pii]
AID - 10.1111/jcmm.17263 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2022 Apr;26(8):2404-2416. doi: 10.1111/jcmm.17263. Epub 2022 Mar 
      5.