Table 1 scRNA-Seq profile of 31 genes known to be involved in idiopathic hypogonadotropic hypogonadism (IHH) as well as genes localized downstream of Nescient-helix-loop-helix 2 (NHL]H2). Expression values correspond to RPKM (Reads Per Kilobase of transcript per Million mapped reads), calculated from the model coefficients using the differential expression model described in [12]. A das]h (“-“) indicates that the gene was not detected in these samples; logFC: log2 fold-change of RNA level; FDR: false discovery rate; n.s.: not significant. HIR Ad, high infertility risk group lacking Ad spermatogonia, LIR Ad+, low infertility risk group displaying Ad spermatogonia, HIR/GnRHa, high infertility risk group, before (prior ) and after (post) GnRHa treatment
Symbol | HIR Ad- | LIR Ad+ | logFC | FDR | HIR/GnRHa | logFC | FDR | ||
|---|---|---|---|---|---|---|---|---|---|
prior | post | ||||||||
Class 1: lower in HIR versus LIR and lower after HIR treatment | |||||||||
FGFR2 | Fiboblast growth factor receptor 2 | 2.05 | 4.3 | -1.25 | 0.0005 | 4.10 | 2.75 | -0.57 | 0.01 |
Class 2: lower in HIR versus LIR but no significant change after HIR treatment | |||||||||
CHD7 | Chromodomain helicase DANN binding protein 7 | 3.94 | 6.53 | -0.72 | 0.001 | 6.46 | 5.20 | n.s. | n.s. |
FGF9 | Fiboblast growth factor 9 | 0.58 | 1.14 | -1.06 | 0.001 | 0.81 | 1.20 | n.s. | n.s. |
FGFR1 | Fiboblast growth factor receptor 1 | 5,26 | 7.40 | -0.49 | 0.019 | 7.60 | 5.94 | n.s. | n.s. |
MET | MET proto-oncogene, receptor tyrosine kinase | 0.40 | 0.98 | -1.28 | 0.007 | 0.78 | 0.95 | n.s. | n.s. |
PROKR1 | Prokineticin receptor 1 | 0.58 | 1.43 | -1.30 | 0.005 | 1.11 | 0.92 | n.s. | n.s. |
PROK2 | Prokineticin receptor 2 | 0.22 | 1.23 | -2.43 | 0.001 | 0.67 | 0.81 | n.s. | n.s. |
SPRY4 | Sprouty RTK signaling antagonist 4 | 0.57 | 1.18 | -1.05 | 0.001 | 1.20 | 1.16 | n.s. | n.s. |
Class 3: no significant difference between HIR and LIR and lower after HIR treatment | |||||||||
DMXL2 | Dmx-like 2 | 9.84 | 12.35 | n.s. | n.s. | 13.31 | 7.58 | -0.81 | 0.001 |
CXCL12 | C-X-C motif chemokine ligand 12 | 13.57 | 13.81 | n.s. | n.s. | 16.84 | 9.53 | -0.82 | 0.003 |
GLCE | Glucuronic acid epimerase | 20.47 | 17.38 | n.s. | n.s. | 21.30 | 11.80 | -0.85 | 0.0006 |
GNRH | Gonadotropin realeasing hormone | 10.37 | 8.95 | n.s. | n.s. | 10.37 | 7.42 | -0.48 | 0.035 |
GNRHR | Gonadotropin realeasing hormone receptor | 2.15 | 2.26 | n.s. | n.s. | 2.94 | 1.72 | -0.76 | 0.002 |
ANOS1 | Anosmin 1 | 13.14 | 11.36 | n.s. | n.s. | 12.71 | 7.35 | -0.79 | 0.0009 |
LEPR | Leptin receptor | 3.40 | 3.31 | n.s. | n.s. | 4.16 | 2.56 | -0.69 | 0.003 |
NDN | Necdin, MAGE family member | 28.99 | 29.08 | n.s. | n.s. | 30.00 | 21.06 | -0.77 | 0.001 |
OTUD4 | OTU deubiquitinase 4 | 23.49 | 23.75 | n.s. | n.s. | 26.78 | 16.72 | -0.67 | 0.005 |
TTF1 | Transcription termination factor 1 | 7.52 | 7.40 | n.s. | n.s. | 8.76 | 6.20 | -0.49 | 0.02 |
VEGFA | Vascular endothelial growth factor A | 9.95 | 11.27 | n.s. | n.s. | 12.22 | 7.58 | -0.68 | 0.005 |
WDR11 | WD repeat domain 11 | 19.99 | 17.77 | n.s. | n.s. | 21.08 | 13.03 | -0.69 | 0.003 |
Class 4: no significant difference between HIR and LIR and higher after HIR treatment | |||||||||
CCD141 | Coiled-coil domain containing 141 | 0.47 | 0.53 | n.s. | n.s. | 0.63 | 1.06 | +0.74 | 0.003 |
EBF2 | Early B-cell Faktor 2 | 0.19 | 0.22 | n.s. | n.s. | 0.24 | 0.84 | +1.76 | 2.07E-05 |
FEZF1 | Fez family zinc finger protein 1 | - | - | - | - | 0.14 | 0.52 | +1.84 | 0.014 |
LEP | Leptin | 0.20 | 0.26 | n.s. | n.s. | 0.02 | 0.80 | +1.59 | 0.001 |
NHLH 1 | Necient helix-loop-helix 1 | - | - | - | - | 0.09 | 0.48 | +1.95 | 0.01 |
SEMA3E | Semaphorin 3E | 0.66 | 1.08 | n.s. | n.s. | 0.23 | 0.72 | +1.59 | 0.0001 |
PCK1 | Phosphoenolpyruvate carboxykinse 1 | - | - | - | - | 0.11 | 0.56 | +2.36 | 0.001 |
PCSK1 | Protein covertase subtilising/kexin 1 | 0.15 | 0.17 | n.s. | n.s. | 0.15 | 0.71 | +2,23 | 2.02E-05 |
TAC3 | Tachykinin precursor 3 | - | - | - | - | 0.23 | 0.87 | +1.87 | 0.011 |
TACR3 | Tachykinin precursor receptor 3 | - | - | - | - | 0.46 | 0.68 | +2.93 | 0.003 |
VAX1 | Ventral anterior homeobox 1 | - | - | - | - | 0.07 | 0.43 | +2.46 | 3.4E-05 |
Class 5: lower in HIR versus LIR and higher after HIR treatment | |||||||||
NHLH2 | Necient helix-loop-helix 2 | 0.18 | 0.59 | -1.65 | 0.0007 | 0.31 | 0.74 | +1.25 | 0.01 |
NHLH2 target genes | |||||||||
NTN1 | Netrin 1 | 0.11 | 0.47 | -2.08 | 0.0005 | 0.28 | 0.51 | +0.84 | 0.03 |
UNC5D | Unc-5 netrin receptor D | 0.26 | 0.57 | -1.10 | 0.003 | 0.44 | 0.98 | +1.15 | 0.002 |
DCC | Deleted in colorectal cancer, netrin 1 receptor | 0.20 | 0.27 | n.s. | n.s. | 0.26 | 0.62 | +1.22 | 0.0003 |