TY - JOUR
T1 - Tmsb10 triggers fetal Leydig differentiation by suppressing the RAS/ERK pathway
AU - Inoue, Miki
AU - Baba, Takashi
AU - Takahashi, Fumiya
AU - Terao, Miho
AU - Yanai, Shogo
AU - Shima, Yuichi
AU - Saito, Daisuke
AU - Sugihara, Kei
AU - Miura, Takashi
AU - Takada, Shuji
AU - Suyama, Mikita
AU - Ohkawa, Yasuyuki
AU - Morohashi, Ken ichirou
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Leydig cells in fetal testes play crucial roles in masculinizing fetuses through androgen production. Gene knockout studies have revealed that growth factors are implicated in fetal Leydig cell (FLC) differentiation, but little is known about the mechanisms regulating this process. We investigate this issue by characterizing FLC progenitor cells using single-cell RNA sequencing. The sequence datasets suggest that thymosin β10 (Tmsb10) is transiently upregulated in the progenitors. While studying the function of Tmsb10, we reveal that platelet-derived growth factor (PDGF) regulates ciliogenesis through the RAS/ERK and PI3K/AKT pathways, and thereby promotes desert hedgehog (DHH)-dependent FLC differentiation. Tmsb10 expressed in the progenitor cells induces their differentiation into FLCs by suppressing the RAS/ERK pathway. Through characterizing the transiently expressed Tmsb10 in the FLC progenitors, this study unveils the molecular process of FLC differentiation and shows that it is cooperatively induced by DHH and PDGF.
AB - Leydig cells in fetal testes play crucial roles in masculinizing fetuses through androgen production. Gene knockout studies have revealed that growth factors are implicated in fetal Leydig cell (FLC) differentiation, but little is known about the mechanisms regulating this process. We investigate this issue by characterizing FLC progenitor cells using single-cell RNA sequencing. The sequence datasets suggest that thymosin β10 (Tmsb10) is transiently upregulated in the progenitors. While studying the function of Tmsb10, we reveal that platelet-derived growth factor (PDGF) regulates ciliogenesis through the RAS/ERK and PI3K/AKT pathways, and thereby promotes desert hedgehog (DHH)-dependent FLC differentiation. Tmsb10 expressed in the progenitor cells induces their differentiation into FLCs by suppressing the RAS/ERK pathway. Through characterizing the transiently expressed Tmsb10 in the FLC progenitors, this study unveils the molecular process of FLC differentiation and shows that it is cooperatively induced by DHH and PDGF.
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U2 - 10.1038/s42003-022-03941-5
DO - 10.1038/s42003-022-03941-5
M3 - Article
C2 - 36109592
AN - SCOPUS:85137850609
SN - 2399-3642
VL - 5
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 974
ER -