Review Article

Advances in Female Germ Cell Induction from Pluripotent Stem Cells

Table 2

Human female GCs differentiation from PSCs in vitro.

Cell typesMain induction methodsAchievementsJournal, year (reference)
Generated cellsCharacterization of generated cells

ESCsSpontaneous differentiation
Suspension culture
Oocyte-like cellsMorphology
Marker expressions (SCP1, SCP3, and GDF9)
Hum Mol Genet, 2004 [61]
ESCsBMP4
Suspension culture
PGCsMorphology
Marker expressions (VASA and SCP3)
Stem cells dev, 2006 [62]
VSELsSpontaneous differentiation
Suspension culture
Oocyte-like cellsMorphology
Marker expressions (C-KIT, VASA, and ZP2)
Differentiation, 2008 [78]
ESCs
iPSCs
Coculture with fetal gonadal cells
Adherent culture
PGCsMorphology
Marker expressions (DAZL, VASA, and SSEA1)
Stem Cells, 2009 [12]
ESCsVASA overexpression
BMP4, BMP7, and BMP8b
Adherent culture
PGCsMorphology
Marker expressions (DAZL, VASA, and SCP3)
Epigenetic analysis
Nature, 2009 [66]
ESCsRA
Suspension culture
Oocyte-like cellsMorphology
Marker expressions (SSEA1, DAZL, and VASA)
Hum Repro, 2009 [63]
iPSCsOverexpression of DAZL and BOULE
BMP4, BMP7, and BMP8b
Adherent culture
PGCsMorphology
Marker expressions (STELLA and DMC1)
Elongated SC formation
Human Mol Genet, 2011 [68]
VSELsSpontaneous differentiation
Adherent culture
Oocyte-like cellsMorphology
Marker expressions (DAZL, ZP4, and GDF9)
Stem Cells Dev, 2011 [79]
ESCs
iPSCs
VASA overexpression
Adherent culture
PGCs
Postmeiotic GCs
Morphology
Marker expressions (GCNF, LHR, and ZP2)
SCP formation analysis
Epigenetic analysis
Stem Cells, 2012 [67]
ESCsSTELLA overexpression
RA
Adherent culture
PGCsMarker expressions (VASA, SCP3, and SOX17)PloS one, 2013 [69]
ESCs
iPSCs
(i) 4i (MAPK, GSK3, P38, and JNK inhibitors), LIF, TGFβ, and bFGF
Adherent culture
(ii) BMP2/4, LIF, SCF, and EGF
Suspension culture
PGCLCsMorphology
Marker expressions (BLIMP1 and STELLA)
Global transcription profiles
Epigenetic analysis
Cell, 2015 [7]
iPSCs(i) ActA and GSK3b inhibitor
Adherent culture
(ii) GMEM/KSR, BMP4, LIF, SCF, and EGF
Suspension culture
iMeLCs
PGCLCs
Morphology
Marker expressions (PRDM14 andSOX17)
Global transcription profiles
Epigenetic analysis
Cell stem cell, 2015 [6]
ESCs
iPSCs
(i) ActA, bFGF, and BMP4 (5 ng/ml)
Adherent culture (ii) Lif and BMP4 (100 ng/ml)
Suspension culture
Mesodermal-like cells
PGCLCs
Morphology
Marker expressions (BLIMP1 and STELLA) global transcription profiles
Epigenetic analysis
EMBO J, 2015 [36]
ESCsOverexpression of DAZL and BOULE
GDF9 and BMP15
Adherent culture
FLCsMorphology
Marker expressions (ZP2, NOBOX, and AMH)
Global transcription profiles
Estradiol secretion
Nat commun, 2017 [74]
VSELsFollicular fluid “serum” medium
Adherent culture
Oocyte-like cellsMorphology
Marker expression (ZP1-3)
Stem Cell Rev Rep, 2018 [80]
iPSCsCoculture with mouse gonadal cells
Suspension culture
PGCLCs
Oogonia-like cells
Morphology
Marker expressions (SCP3, REC8 and STRA8)
Transcriptome dynamics
Epigenetic analysis
X chromosome activity
Science, 2018 [8]

ESCs: embryonic stem cells; iPSCs: induced pluripotent stem cells; VSELs: very small embryonic-like stem cells; iMeLCs: incipient mesoderm-like cells; PGCs: primordial germ cells; PGCLCs: primordial germ cell-like cells; FLCs: follicle-like cells; SCP: synaptonemal complex protein.