Transdifferentiation of human male germline stem cells to hepatocytes<i>in vivo</i>via the transplantation under renal capsules

Chen, Zheng; Niu, Minghui; Sun, Min; Yuan, Quan; Yao, Chencheng; Hou, Jingmei; Wang, Hong; Wen, Lei; Fu, Han; Zhou, Fan; Li, Zheng; He, Zuping

doi:10.18632/oncotarget.14713

Cited by 13 publications

(8 citation statements)

References 39 publications

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“…Fourth, it has recently been demonstrated that both rodent and human SSCs can acquire pluripotency to become embryonic stem cell (ESC)-like cells that differentiate to mature and functional cells of the three germ cell layers. 2 , 3 , 4 Finally, we and peers have recently reported that mouse and human SSCs are able to directly transdifferentiate to cells with phenotypic and functional hepatocytes; 5 , 6 , 7 neuron; 8 and various kinds of tissues, including prostatic, uterine, and skin epithelium. 9 As such, human SSCs have great applications in regenerative medicine to treat various kinds of human diseases.…”

Section: Introductionmentioning

confidence: 95%

PAK1 Promotes the Proliferation and Inhibits Apoptosis of Human Spermatogonial Stem Cells via PDK1/KDR/ZNF367 and ERK1/2 and AKT Pathways

Zhang

Yuan

et al. 2018

Molecular Therapy - Nucleic Acids

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Spermatogonial stem cells (SSCs) have significant applications in reproductive and regenerative medicine. However, nothing is known about genes in mediating human SSCs. Here we have explored for the first time the function and mechanism of P21-activated kinase 1 (PAK1) in regulating the proliferation and apoptosis of the human SSC line. PAK1 level was upregulated by epidermal growth factor (EGF), but not glial cell line-derived neurotrophic factor (GDNF) or fibroblast growth factor 2 (FGF2). PAK1 promoted proliferation and DNA synthesis of the human SSC line, whereas PAK1 suppressed its apoptosis in vitro and in vivo. RNA sequencing identified that PDK1, ZNF367, and KDR levels were downregulated by PAK1 knockdown. Immunoprecipitation and Western blots demonstrated that PAK1 interacted with PDK1. PDK1 and KDR levels were decreased by ZNF367-small interfering RNAs (siRNAs). The proliferation of the human SSC line was reduced by PDK1-, KDR-, and ZNF367-siRNAs, whereas its apoptosis was enhanced by these siRNAs. The levels of phos-ERK1/2, phos-AKT, and cyclin A were decreased by PAK1-siRNAs. Tissue arrays showed that PAK1 level was low in non-obstructive azoospermia patients. Collectively, PAK1 was identified as the first molecule that controls proliferation and apoptosis of the human SSC line through PDK1/KDR/ZNF367 and the ERK1/2 and AKT pathways. This study provides data on novel gene regulation and networks underlying the fate of human SSCs, and it offers new molecular targets for human SSCs in translational medicine.

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Section: Introductionmentioning

confidence: 95%

PAK1 Promotes the Proliferation and Inhibits Apoptosis of Human Spermatogonial Stem Cells via PDK1/KDR/ZNF367 and ERK1/2 and AKT Pathways

Zhang

Yuan

et al. 2018

Molecular Therapy - Nucleic Acids

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“…The fate determinations of SSCs, including the self-renewal, differentiation, and apoptosis, are essential for the maintenance of human spermatogenesis [ 1 ]. Notably, human and rodent SSCs have the great plasticity, as evidenced by the findings that they are able to become embryonic stem cell-like cells that differentiate into all cell types of three germ layersand can be transdifferentiated to other cell lineages [ 2 , 3 , 4 , 5 , 6 ]. As such, human SSCs could have significant applications in both reproductive and regenerative medicine.…”

Section: Novel Gene Regulation In the Fate Decisions Of Human Sscsmentioning

confidence: 99%

Novel Gene Regulation in Normal and Abnormal Spermatogenesis

Chen

Cheng

et al. 2021

Cells

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Spermatogenesis is a complex and dynamic processwhich is precisely controlledby genetic and epigenetic factors. With the development of new technologies (e.g., single-cell RNA sequencing), increasingly more regulatory genes related to spermatogenesis have been identified. In this review, we address the roles and mechanisms of novel genes in regulatingthenormal and abnormal spermatogenesis. Specifically, we discussed the functions and signaling pathways of key new genes in mediating the proliferation, differentiation, and apoptosis of rodent and human spermatogonial stem cells (SSCs), as well as in controlling the meiosis of spermatocytes and other germ cells. Additionally, we summarized the gene regulation in the abnormal testicular microenvironment or the niche by Sertoli cells, peritubularmyoid cells, and Leydig cells. Finally, we pointed out the future directions for investigating the molecular mechanisms underlying human spermatogenesis. This review could offer novel insights into genetic regulation in the normal and abnormal spermatogenesis, and it provides new molecular targets for gene therapy of male infertility.

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“…In male, spermatogonial stem cells (SSCs) undergo self-renewal to ensure at the same time the maintenance of the stem cells pool and the differentiation to spermatocytes and spermatids. SSCs can also dedifferentiate into embryonic stem (ES)-like cells to acquire pluripotency in vitro (Conrad et al, 2008) and they are able to be reprogrammed to transdifferentiate to cell lineages of other tissues and for this reason SSCs have relevant applications in treating male infertility (Chen et al, 2017). Distinct circRNA expression profiles in different types of male germ cells indicate an important role exerted by circRNAs in the control of self-renewal and differentiation processes of SSCs (Zhou et al, 2019).…”

Section: Circrnas In Reproductive System and Germ Cell Developmentmentioning

confidence: 99%

Circular RNAs in Embryogenesis and Cell Differentiation With a Focus on Cancer Development

Agostino¹,

Riccioli

Cesaris

et al. 2020

Front. Cell Dev. Biol.

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In the recent years thousands of non-coding RNAs have been identified, also thanks to highthroughput sequencing technologies. Among them, circular RNAs (circRNAs) are a well-represented class characterized by the high sequence conservation and cell type specific expression in eukaryotes. They are covalently closed loops formed through back-splicing. Recently, circRNAs were shown to regulate a variety of cellular processes functioning as miRNA sponges, RBP binding molecules, transcriptional regulators, scaffold for protein translation, as well as immune regulators. A growing number of studies are showing that deregulated expression of circRNAs plays important and decisive actions during the development of several human diseases, including cancer. The research on their biogenesis and on the various molecular mechanisms in which they are involved is going very fast, however, there are still few studies that address their involvement in embryogenesis and eukaryotic development. This review has the intent to describe the most recent progress in the study of the biogenesis and molecular activities of circRNAs providing insightful information in the field of embryogenesis and cell differentiation. In addition, we describe the latest research on circRNAs as novel promising biomarkers in diverse types of tumors.

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Transdifferentiation of human male germline stem cells to hepatocytesin vivovia the transplantation under renal capsules

Cited by 13 publications

References 39 publications

PAK1 Promotes the Proliferation and Inhibits Apoptosis of Human Spermatogonial Stem Cells via PDK1/KDR/ZNF367 and ERK1/2 and AKT Pathways

PAK1 Promotes the Proliferation and Inhibits Apoptosis of Human Spermatogonial Stem Cells via PDK1/KDR/ZNF367 and ERK1/2 and AKT Pathways

Novel Gene Regulation in Normal and Abnormal Spermatogenesis

Circular RNAs in Embryogenesis and Cell Differentiation With a Focus on Cancer Development

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