Mapping Human Pluripotent Stem Cell-derived Erythroid Differentiation by Single-cell Transcriptome Analysis.
Differentiation trajectory
Erythropoiesis
Hematopoiesis
iPSC
scRNA-seq
Journal
Genomics, proteomics & bioinformatics
ISSN: 2210-3244
Titre abrégé: Genomics Proteomics Bioinformatics
Pays: China
ID NLM: 101197608
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
22
01
2021
revised:
22
01
2021
accepted:
06
03
2021
pubmed:
21
7
2021
medline:
24
3
2022
entrez:
20
7
2021
Statut:
ppublish
Résumé
There is an imbalance between the supply and demand of functional red blood cells (RBCs) in clinical applications. This imbalance can be addressed by regenerating RBCs using several in vitro methods. Induced pluripotent stem cells (iPSCs) can handle the low supply of cord blood and the ethical issues in embryonic stem cell research, and provide a promising strategy to eliminate immune rejection. However, no complete single-cell level differentiation pathway exists for the iPSC-derived erythroid differentiation system. In this study, we used iPSC line BC1 to establish a RBC regeneration system. The 10X Genomics single-cell transcriptome platform was used to map the cell lineage and differentiation trajectory on day 14 of the regeneration system. We observed that iPSC differentiation was not synchronized during embryoid body (EB) culture. The cells (on day 14) mainly consisted of mesodermal and various blood cells, similar to the yolk sac hematopoiesis. We identified six cell classifications and characterized the regulatory transcription factor (TF) networks and cell-cell contacts underlying the system. iPSCs undergo two transformations during the differentiation trajectory, accompanied by the dynamic expression of cell adhesion molecules and estrogen-responsive genes. We identified erythroid cells at different stages, such as burst-forming unit erythroid (BFU-E) and orthochromatic erythroblast (ortho-E) cells, and found that the regulation of TFs (e.g., TFDP1 and FOXO3) is erythroid-stage specific. Immune erythroid cells were identified in our system. This study provides systematic theoretical guidance for optimizing the iPSC-derived erythroid differentiation system, and this system is a useful model for simulating in vivo hematopoietic development and differentiation.
Identifiants
pubmed: 34284135
pii: S1672-0229(21)00153-4
doi: 10.1016/j.gpb.2021.03.009
pmc: PMC8864192
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
358-376Informations de copyright
Copyright © 2021 The Author. Published by Elsevier B.V. All rights reserved.
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