Lin28a promotes self-renewal and proliferation of dairy goat spermatogonial stem cells (SSCs) through regulation of mTOR and PI3K/AKT

Abstract

Lin28a is a conserved RNA-binding protein that plays an important role in development, pluripotency, stemness maintenance, proliferation and self-renewal. Early studies showed that Lin28a serves as a marker of spermatogonial stem cells (SSCs) and promotes the proliferation capacity of mouse SSCs. However, there is little information about Lin28a in livestock SSCs. In this study, we cloned Capra hircus Lin28a CDS and found that it is evolutionarily conserved. Lin28a is widely expressed in different tissues of Capra hircus, but is expressed at a high level in the testis. Lin28a is specifically located in the cytoplasm of Capra hircus spermatogonial stem cells and may also be a marker of dairy goat spermatogonial stem cells. Lin28a promoted proliferation and maintained the self-renewal of GmGSCs-I-SB in vivo and in vitro. Lin28a-overexpressing GmGSCs-I-SB showed an enhanced proliferation rate, which might be due to increased PCNA expression. Moreover, Lin28a maintained the self-renewal of GmGSCs-I-SB by up-regulating the expression of OCT4, SOX2, GFRA1, PLZF and ETV5. Furthermore, we found that Lin28a may activate the AKT, ERK, and mTOR signaling pathways to promote the proliferation and maintain the self-renewal of GmGSCs-I-SB.

Compared proteomic analysis of 8‐ and 32‐week‐old postnatal porcine ovaries

“…However, we found that products of genes for stem cell maintenance, including Bcl9l, Cdh2,and Jag1; stem cell proliferation, including Aspm, Numbl, and Nkap; and positive regulation of stem cell maintenance, such as Yap1, were present in ovaries of 8 and 32‐week‐old animals, suggesting existence of stem cells in both (Table S1). Proteins in the mTOR and PI3K‐AKT signalling pathways, involved in maintaining stem cell renewal, were more highly expressed in the 8‐week than in the 32‐week ovaries. Compared with at 8‐week ovaries, the 32‐week ovaries contained more metabolism‐related proteins, responsible for supporting oocyte maturation.…”

SOX2 recruits KLF4 to regulate nasopharyngeal carcinoma proliferation via PI3K/AKT signaling

“… 31 , 32 ). SOX2 was also shown to regulate Lin28a to activate the AKT signaling pathway thereby promoting the proliferation and maintain the self-renewal of GmGSCs-I-SB 12 . In our present study, by performing KEGG pathway analyses of the microarray gene expression data in shSOX2-HNE-1 cell line, we found that knockdown of SOX2 was significantly correlated with the PI3K/AKT signaling pathway.…”

“…It has been reported that SOX2 works as transcriptional activators in reprogramming human fibroblasts 11 . SOX2 is also shown as a regulator of PI3K/AKT signaling in spermatogonial stem cells 12 . Moreover, SOX2 was reported to promote tumorigenesis, progression, and metastasis in multiple types of cancer through controlling stem cell activity 13 , 14 .…”

Newcastle disease virus V protein inhibits apoptosis in DF-1 cells by downregulating TXNL1

“…The primer sequences for TXNL1 were designed according to the published Gallus TXNL1 (XM_424463.5), as shown in Table 1. TXNL1 was amplified from the CEF, and the cDNA was synthesized using a reverse transcription polymerase chain reaction (RT-PCR) [23]. Then, enzyme digestion and ligation were performed, and the specific fragments were cloned into the pCMV-HA cloning vector (TaKaRa, Dalian, China).…”