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Int J Stem Cells. 2019 Jul 31;12(2):240-250. doi: 10.15283/ijsc18137.

Comparative Evaluation of Hormones and Hormone-Like Molecule in Lineage Specification of Human Induced Pluripotent Stem Cells.

Choi SA1,2, An JH1,2,3, Lee SH1,2, Lee GH1,2, Yang HJ1,2, Jeong PS1,2, Cha JJ1,2, Lee S1,2, Park YH1,2,3, Song BS1,2,3, Sim BW1,2, Kim YH2,3, Kim JS2,3,4, Jin YB2, Huh JW2,3, Lee SR2,3, Lee JH1,2, Kim SU1,2,3.

Author information

1
Futuristic Animal Resource & Research Center (FARRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Korea.
2
National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Korea.
3
Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Korea.
4
Primate Resource Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, Korea.

Abstract

Background and Objectives:

Proficient differentiation of human pluripotent stem cells (hPSCs) into specific lineages is required for applications in regenerative medicine. A growing amount of evidences had implicated hormones and hormone-like molecules as critical regulators of proliferation and lineage specification during in vivo development. Therefore, a deeper understanding of the hormones and hormone-like molecules involved in cell fate decisions is critical for efficient and controlled differentiation of hPSCs into specific lineages. Thus, we functionally and quantitatively compared the effects of diverse hormones (estradiol 17-β (E2), progesterone (P4), and dexamethasone (DM)) and a hormone-like molecule (retinoic acid (RA)) on the regulation of hematopoietic and neural lineage specification.

Methods and Results:

We used 10 nM E2, 3 µM P4, 10 nM DM, and 10 nM RA based on their functional in vivo developmental potential. The sex hormone E2 enhanced functional activity of hematopoietic progenitors compared to P4 and DM, whereas RA impaired hematopoietic differentiation. In addition, E2 increased CD34+CD45+ cells with progenitor functions, even in the CD43- population, a well-known hemogenic marker. RA exhibited lineage-biased potential, preferentially committing hPSCs toward the neural lineage while restricting the hematopoietic fate decision.

Conclusions:

Our findings reveal unique cell fate potentials of E2 and RA treatment and provide valuable differentiation information that is essential for hPSC applications.

KEYWORDS:

Cell fate decision; Estradiol-17β; Hematopoietic differentiation; Human induced pluripotent stem cells; Retinoic acid; lineage specification

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