SALL3 expression balance underlies lineage biases in human induced pluripotent stem cell differentiation

Takuya Kuroda, Satoshi Yasuda, Shiori Tachi, Satoko Matsuyama, Shinji Kusakawa, Keiko Tano, Takumi Miura, Akifumi Matsuyama and Yoji Sato ()
Additional contact information
Takuya Kuroda: Division of Cell-Based Therapeutic Products, National Institute of Health Sciences
Satoshi Yasuda: Division of Cell-Based Therapeutic Products, National Institute of Health Sciences
Shiori Tachi: Division of Cell-Based Therapeutic Products, National Institute of Health Sciences
Satoko Matsuyama: Division of Cell-Based Therapeutic Products, National Institute of Health Sciences
Shinji Kusakawa: Division of Cell-Based Therapeutic Products, National Institute of Health Sciences
Keiko Tano: Division of Cell-Based Therapeutic Products, National Institute of Health Sciences
Takumi Miura: Division of Cell-Based Therapeutic Products, National Institute of Health Sciences
Akifumi Matsuyama: Fujita Health University
Yoji Sato: Division of Cell-Based Therapeutic Products, National Institute of Health Sciences

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract Clinical applications of human induced pluripotent stem cells (hiPSCs) are expected, but hiPSC lines vary in their differentiation propensity. For efficient selection of hiPSC lines suitable for differentiation into desired cell lineages, here we identify SALL3 as a marker to predict differentiation propensity. SALL3 expression in hiPSCs correlates positively with ectoderm differentiation capacity and negatively with mesoderm/endoderm differentiation capacity. Without affecting self-renewal of hiPSCs, SALL3 knockdown inhibits ectoderm differentiation and conversely enhances mesodermal/endodermal differentiation. Similarly, loss- and gain-of-function studies reveal that SALL3 inversely regulates the differentiation of hiPSCs into cardiomyocytes and neural cells. Mechanistically, SALL3 modulates DNMT3B function and DNA methyltransferase activity, and influences gene body methylation of Wnt signaling-related genes in hiPSCs. These findings suggest that SALL3 switches the differentiation propensity of hiPSCs toward distinct cell lineages by changing the epigenetic profile and serves as a marker for evaluating the hiPSC differentiation propensity.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-09511-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09511-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-09511-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().