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Table 2 Differentiation of multipotent fetal stem cells into germ cells

From: Multipotent fetal stem cells in reproductive biology research

Stem cells

Differentiation

Germ cell sex

References

Amniotic fluid

AFSCs

Follicular fluid triggered BMP15, ZP1, ZP2, and ZP3-positive oocyte-like cell differentiation

Female

[154]

Germ cell maturation factors or follicular fluid induced the expression of germ cell markers

Female

[215]

Follicular fluid induced the development of meiotic germ cells expressing markers for folliculogenesis and oogenesis

Female

[156]

AF-MSCs

Stem cells from the amniotic fluid without c-Kit selection were developed to embryoid bodies and proven to express PGC markers and markers of early germ cell development, including ACR, Dazl, Fragilis, Piwil2, RNf17, Stella, Stra8, and Vasa

Not applicable

[216]

Amniotic membrane

AM-MSCs

Incubation with BMP4 and RA induced PGC/spermatogonia-like cells (positive for Dazl, Itgb1, Mvh, Piwil2, and Stra8)

Male

[157]

BMP4 induced the differentiation of germ/oocyte-like cells positive for Oct4, SSEA4, Vasa, and the oocyte-related gene Gdf9

Female

[158]

Induction of PGC markers upon treatment with RA (induction of c-Kit, SSEA4, Vasa; downregulation of Oct4)

Male

[159]

AECs

Medium containing serum substitute supplement triggered the development of oocyte-like cells expressing Dazl, Vasa, the oocyte-specific markers Gdf9 and ZP3, and the meiosis-specific markers DMC1 and SYCP3

Female

[155]

Chorion laeve

CL-MSCs

BMP4 induced the differentiation of germ/oocyte-like cells positive for Oct4, SSEA4, Vasa, and the oocyte-related gene Gdf9

Female

[158]

Wharton´s jelly

WJ-MSCs

RA/testosterone and testicular cell-conditioned medium induced CD49, c-Kit, Oct4, Stella, and Vasa-positive GCs

Male

[217]

Cultivation with follicular fluid induced oocyte-like cells positive for Dazl, Oct4, Stra8, SYCP3, Vasa, ZP2, and ZP3

Female

[218]

Figlα transfection/cultivation with follicular fluid induced oocyte-like cells positive for Dazl, Oct4, Stra8, Vasa, ZP2, and ZP3

Female

[219]

BMP4 induced DMRT1, PLZF, Stra8, and SYCP3-positive GCs and some sperm-like cells

Male

[220]

RA/testosterone and testicular-cell-conditioned medium induced germ cells positive for Dazl, SYCP3, and Vasa

Male

[221]

BMP4/RA-mediated induction of PGC markers SSEA4, Stella, SYCP3, and Vasa

Male

[222]

BMP4/RA and cultivation on amniotic epithelial and chorionic plate cells drove the development of GCs expressing Dazl, Fragilis, β1-integrin, α6-integrin, Oct4, Piwil2, PLZF, Stra8, and Vasa

Male

[223]

Co-cultivation with placental cells induced germ/oocyte-like cells positive for Oct4 and Vasa and weakly positive for the oocyte markers Gdf9 and ZP3

Female

[224]

Follicular fluid, FSH, LH, and estradiol induced oocyte-like cells positive for Gdf9, SYCP3, ZP1, ZP2, and ZP3

Female

[225]

Co-cultivation with Sertoli cells induced GCs positive for Dazl, Stella, and Vasa

Male

[226]

BMP4/RA and testicular and placental culture condition induced GCs positive for c-Kit, Dazl, Piwil2, and Vasa

Male

[227]

Human WJ-MSCs differentiated into germ-like cells upon injection into mouse seminiferous tubules

Male

[161]

CD61 overexpression and BMP4 triggered ACR, Prm1, Stra8, and SYCP3-positive GCs

Male

[228]

RA/LIF/GDNF/putrescine/testosterone/FSH and Sertoli/Epididymal cell co-cultivation triggered the development of haploid spermatid-like cells positive for ACR, Dazl, ODF2, Prm1, and Vasa

Male

[160]

BMP4 induced the differentiation of germ/oocyte-like cells positive for Oct4, SSEA4, Vasa, and the oocyte-related gene Gdf9

Female

[158]

RA and Sertoli cell-conditioned medium induced GCs positive for Prm1 and Stra8

Male

[229]

RA and Sertoli cell-conditioned medium triggered the differentiation of GCs with diminished Oct4 and PLZF expression and upregulated ACR, Prm1, Stra8, and SYCP3. Some secondary spermatocytes and spermatid-like cells developed

Male

[230]

BMP4/RA and polarized or non-polarized red light irradiation induced Dazl, Fragilis, SYCP3, and Vasa expression

Male

[231]

Follicular fluid and cumulus cells-conditioned medium triggered the development of oocyte-like cells positive for c-Kit, Gdf9, SYCP3, Vasa, ZP1, ZP2, and ZP3

Female

[232]

Co-cultivation with testicular cells induced Fragilis, SYCP3, and Vasa-positive GCs

Male

[233]

  1. AFSCs, c-Kit + amniotic fluid stem cells; AF-MSCs, amniotic fluid mesenchymal stem cells; AM-MSCs, amniotic membrane mesenchymal stem cells; AECs, amniotic epithelial cells; CL-MSCs, chorion laeve mesenchymal stem cells; WJ-MSCs, Wharton’s jelly mesenchymal stem cells; UCB-MSCs, umbilical cord blood mesenchymal stem cells; UCB-HSCs, umbilical cord blood hematopoietic stem cells; CP-MSCs, chorionic plate mesenchymal stem cells; CV-MSCs, chorionic villi mesenchymal stem cells
  2. ACR, Acrosin; BMP, bone morphogenetic protein; CD, cluster of differentiation; CD61, also called integrin-β3; c-Kit, tyrosine-protein kinase Kit (receptor for SCF); Dazl, deleted in azoospermia like protein; DMC1, DNA meiotic recombinase 1; DMRT1, doublesex and Mab-3 related transcription factor 1; Figlα; folliculogenesis specific basic helix-loop-helix protein; Fragilis, an interferon-inducible gene coding for a transmembrane protein; FSH, follicle-stimulating hormone; GC, germ cell; Itgb1, integrin β-1; Gdf9, growth differentiation factor-9; GDNF, glial cell line-derived neurotrophic factor; LH, luteinizing hormone; LIF, leukemia inhibitory factor; Mvh, mouse Vasa homolog; Oct4, octamer-binding transcription factor 4; ODF2, outer dense fiber of sperm tails 2 protein; PGC, primordial germ cells; Piwil2, Piwi like RNA-mediated gene silencing 2 protein; PLZF, promyelocytic leukemia zinc finger; Prm1, protamine 1; RA, retinoic acid; Rnf17, ring finger protein 17; SSEA, stage specific embryonic antigen; Stella, also known as developmental pluripotency associated 3 protein; Stra8, stimulated by retinoic acid 8 protein; SYCP3, synaptonemal complex protein 3; Vasa, also designated DDX4 - DEAD-box helicase 4; ZP, zona pellucida sperm-binding protein or zona pellucida glycoprotein.