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Title: Extracellular laminin regulates hematopoietic potential of pluripotent stem cells through integrin β1-ILK-β-catenin-JUN axis
Authors: Yuzuriha, Akinori
Nakamura, Sou
Sugimoto, Naoshi  kyouindb  KAKEN_id  orcid (unconfirmed)
Kihara, Shunsuke
Nakagawa, Masato  kyouindb  KAKEN_id  orcid (unconfirmed)
Yamamoto, Takuya
Sekiguchi, Kiyotoshi
Eto, Koji
Author's alias: 杠, 明憲
中村, 壮
杉本, 直志
中川, 誠人
山本, 拓也
江藤, 浩之
Keywords: Hematopoietic cell differentiation
Integrin β1
Canonical Wnt/β-catenin pathway
Pluripotent stem cells
Issue Date: May-2021
Publisher: Elsevier BV
Journal title: Stem Cell Research
Volume: 53
Thesis number: 102287
Abstract: Recombinant matrices have enabled feeder cell-free maintenance cultures of human pluripotent stem cells (hPSCs), with laminin 511-E8 fragment (LM511-E8) being widely used. However, we herein report that hPSCs maintained on LM511-E8 resist differentiating to multipotent hematopoietic progenitor cells (HPCs), unlike hPSCs maintained on LM421-E8 or LM121-E8. The latter two LM-E8s bound weakly to hPSCs compared with LM511-E8 and activated the canonical Wnt/β-catenin signaling pathway. Moreover, the extracellular LM-E8-dependent preferential hematopoiesis was associated with a higher expression of integrin β1 (ITGB1) and downstream integrin-linked protein kinase (ILK), β-catenin and phosphorylated JUN. Accordingly, the lower coating concentration of LM511-E8 or addition of a Wnt/β-catenin signaling activator, CHIR99021, facilitated higher HPC yield. In contrast, the inhibition of ILK, Wnt or JNK by inhibitors or mRNA knockdown suppressed the HPC yield. These findings suggest that extracellular laminin scaffolds modulate the hematopoietic differentiation potential of hPSCs by activating the ITGB1-ILK-β-catenin-JUN axis at the undifferentiated stage. Finally, the combination of low-concentrated LM511-E8 and a revised hPSC-sac method, which adds bFGF, SB431542 and heparin to the conventional method, enabled a higher yield of HPCs and higher rate for definitive hematopoiesis, suggesting a useful protocol for obtaining differentiated hematopoietic cells from hPSCs in general.
Description: 血液細胞へ効率よく変化させる弱い接着を明らかに --血液細胞の産生効率を向上--. 京都大学プレスリリース. 2021-03-31.
Stuck stem cells are no good at making blood. 京都大学プレスリリース. 2021-03-31.
Rights: © 2021 The Authors. Published by Elsevier B.V. This is an open access article under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Public License (CC BY-NC-ND license)
DOI(Published Version): 10.1016/j.scr.2021.102287
PubMed ID: 33813173
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