Masanaga Muto

Masanaga Muto

Researcher (Ema-G)

Assistant Professor
Research Field
Reproductive Biology

Research Overview

Exploring Developmental Potential of Inner Cell Mass and Trophectoderm in Cynomolgus Monkeys

The mammalian pre-implantation embryos establish two distinct cell lineages by the time of blastocyst formation: epiblast and trophoblast cells. Studying mechanisms regulating differentiation of epiblast and trophoblast cells is clinically relevant for infertility and miscarriage. There are so many reports utilizing the mouse epiblast-derived embryonic stem (ES) cells and gene modified mouse models for investigating of the mechanisms of embryonic development. The recent reports suggested that the gene expression profiles related to pluripotency and differentiation markers are significantly difference between human and mouse ES cells. Furthermore, mouse ES cells do not differentiate into trophoblast cells, however, human ES cells are able to form trophoblast-like cells and express genes characteristic of trophoblast cells which is specialized cell of the placenta. These results suggesting that the human epiblast is not characterized by the conventional developmental mechanisms which has been studied using mouse models. However, the studying of human embryonic development is utilizing only in vitro human ES cell models, thus the in vivo differentiation mechanism is still poorly understood. We will utilize cynomolgus monkey to elucidate the new insight into the primate-specific mechanisms of developmental plasticity between epiblast and trophoblast cell in the mammalian blastocyst formation.


Masanaga Muto obtained his PhD from Osaka University (2016) and moved to U.S. and undertook postdoctoral training at University of Kansas Medical Center (2016-2019). He has been working as Assistant Professor in the Research Center for Animal Life Science of Shiga University of Medical Science.


Muto M, Chakraborty D, Varberg KM, Moreno-Irusta A, Iqbal K, Scott RL, McNally RP, Choudhury RH, Aplin JD, Okae H, Arima T, Matsumoto S, Ema M, Mast AE, Grundberg E, Soares MJ.
Intersection of Regulatory Pathways Controlling Hemostasis and Hemochorial Placentation
Proc Natl Acad Sci U S A. 2021 Dec 14 118 (50) e2111267118 doi:10.1073/pnas.2111267118

Varberg KM, Iqbal K, Muto M, Simon ME, Scott RL, Kozai K, Choudhury RH, Aplin JD, Biswell R, Gibson M, Okae H, Arima T, Vivian JL, Grundberg E, Soares MJ.
ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development
Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):e2016517118. doi:10.1073/pnas.2016517118

Seita Y, Morimura T, Watanabe N, Iwatani C, Tsuchiya H, Nakamura S, Suzuki T, Yanagisawa D, Tsukiyama T, Nakaya M, Okamura E, Muto M, Ema M, Nishimura M, Tooyama I.
Generation of Transgenic Cynomolgus Monkeys Overexpressing the Gene for Amyloid-β Precursor Protein
J Alzheimers Dis. 2020;75(1):45-60. doi: 10.3233/JAD-191081

Tobita T, Kiyozumi D,  Muto M, Noda T, Ikawa M.
Lvrn expression is not critical for mouse placentation.
J Reprod Dev. 2019 Jun 14;65(3):239-244. doi: 10.1262/jrd.2018-157. Epub 2019

Aoki A, Nakashima A, Kusabiraki T, Ono Y, Yoshino O, Muto M, Kumasawa K, Yoshimori T, Ikawa M, Saito S.
Trophoblast-Specific Conditional Atg7 Knockout Mice Develop Gestational Hypertension.
The American Journal of Pathology. 188(11):2474-2486. 2018

Chakraborty D, Muto M, Soares MJ.
Ex vivo Trophoblast-specific Genetic Manipulation Using Lentiviral Delivery.
Bio-Protocol. pii; 7(24) e2652, 2017

Onda K, Tong S, Beard S, Binder N, Muto M, Senadheera SN, Parry L, Dilworth M, Renshall L, Brownfoot F, Hastie R, Tuohey L, Palmer K, Hirano T, Ikawa M, Kaitu'u-Lino T, Hannan NJ.
Proton Pump Inhibitors Decrease Soluble fms-Like Tyrosine Kinase-1 and Soluble Endoglin Secretion, Decrease Hypertension, and Rescue Endothelial Dysfunction.
Hypertension. 69(3):457-468. 2017

Muto M, Fujihara Y, Tobita T, Kiyozumi D, Ikawa M.
Lentiviral vector mediated complementation restored fetal viability but not placental hyperplasia in Plac1 deficient mice.
Biology of Reproduction, 94(1):6. 2016

Latos PA, Sienerth AR, Murray A, Senner CE, Muto M, Ikawa M, Oxley D, Burge S, Cox B, Hemberger M.
Elf5-centered transcription factor hub controls trophoblast stem cell self-renewal and differentiation through stoichiometry-sensitive shifts in target gene networks.4
Genes & Development. 29(23):2435-48. 2015

Miyata H, Satouh Y, Mashiko D, Muto M, Nozawa K, Shiba K, Fujihara Y, Isotani A, Inaba K, Ikawa M.
Sperm calcineurin inhibition prevents mouse fertility with implications for male contraceptive.
Science. 350(6259):442-5. 2015


American Heart Association Postdoctoral Fellowship (January 2019 to July 2019)
Lalor Foundation Postdoctoral Fellowship (July 2016 to June 2017)
2017 Poster Award Winner, The 14th Annual Gilbert S. Greenwald Symposium on Reproduction and Regenerative Medicine (2017)
Maruho Trainee Travel Grant (SSR 48th Annual Meeting, 2015)
Research Fellowship for Young Scientists (DC2), Japan Society for the Promotion of Science (JSPS) (April 2015 to June 2016)

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