Derivation of human primordial germ cell-like cells in an embryonic-like culture

Sajedeh Nasr Esfahani; Yi Zheng; Auriana Arabpour; Agnes M Resto Irizarry; Norio Kobayashi; Xufeng Xue; Yue Shao; Cheng Zhao; Nicole L Agranonik; Megan Sparrow; Timothy J Hunt; Jared Faith; Mary Jasmine Lara; Qiu Ya Wu; Sherman Silber; Sophie Petropoulos; Ran Yang; Kenneth R Chien; Amander T Clark; Jianping Fu

doi:10.1038/s41467-023-43871-2

Derivation of human primordial germ cell-like cells in an embryonic-like culture

Nat Commun. 2024 Jan 2;15(1):167. doi: 10.1038/s41467-023-43871-2.

Authors

Sajedeh Nasr Esfahani^#¹, Yi Zheng^#^{1

2}, Auriana Arabpour^#^{3

4

5}, Agnes M Resto Irizarry¹, Norio Kobayashi¹, Xufeng Xue¹, Yue Shao⁶, Cheng Zhao⁷, Nicole L Agranonik⁵, Megan Sparrow⁵, Timothy J Hunt⁵, Jared Faith⁵, Mary Jasmine Lara⁵, Qiu Ya Wu⁵, Sherman Silber⁸, Sophie Petropoulos^{7

9

10

11}, Ran Yang¹², Kenneth R Chien¹², Amander T Clark^{13

14

15}, Jianping Fu^{16

17

18}

Affiliations

¹ Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
² Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY, 13244, USA.
³ Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
⁴ Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
⁵ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
⁶ Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, School of Aerospace Engineering, Tsinghua University, 100084, Beijing, China.
⁷ Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynecology, Karolinska Instituet, 14186, Stockholm, Sweden.
⁸ Infertility Center of St. Louis, St. Luke's Hospital, St. Louis, MO, 63017, USA.
⁹ Département de Médecine, Université de Montréal, Montréal, QC, Canada.
¹⁰ Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Axe Immunopathologie, Montreal, QC, H2X 19A, Canada.
¹¹ Département de Médecine, Molecular Biology Programme, Université de Montréal, Montréal, QC, Canada.
¹² Department of Cell and Molecular Biology, Karolinska Institutet, 171 77, Stockholm, Sweden.
¹³ Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA. clarka@ucla.edu.
¹⁴ Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, 90095, USA. clarka@ucla.edu.
¹⁵ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, 90095, USA. clarka@ucla.edu.
¹⁶ Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA. jpfu@umich.edu.
¹⁷ Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. jpfu@umich.edu.
¹⁸ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA. jpfu@umich.edu.

^# Contributed equally.

Abstract

Primordial germ cells (PGCs) are the embryonic precursors of sperm and eggs. They transmit genetic and epigenetic information across generations. Given the prominent role of germline defects in diseases such as infertility, detailed understanding of human PGC (hPGC) development has important implications in reproductive medicine and studying human evolution. Yet, hPGC specification remains an elusive process. Here, we report the induction of hPGC-like cells (hPGCLCs) in a bioengineered human pluripotent stem cell (hPSC) culture that mimics peri-implantation human development. In this culture, amniotic ectoderm-like cells (AMLCs), derived from hPSCs, induce hPGCLC specification from hPSCs through paracrine signaling downstream of ISL1. Our data further show functional roles of NODAL, WNT, and BMP signaling in hPGCLC induction. hPGCLCs are successfully derived from eight non-obstructive azoospermia (NOA) participant-derived hPSC lines using this biomimetic platform, demonstrating its promise for screening applications.

MeSH terms

Cell Differentiation
Cell Line
Germ Cells / metabolism
Humans
Male
Pluripotent Stem Cells*
Semen*
Signal Transduction

Abstract

MeSH terms

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