Transcriptional regulatory networks underlying the reprogramming of spermatogonial stem cells to multipotent stem cells
| Autor: | Daehee Hwang, Jinhyuk Bhin, Kye Seong Kim, Hyung Joon Kim, Hoe Su Jeong, Dong Ryul Lee |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Pluripotent Stem Cells 0301 basic medicine Homeobox protein NANOG Clinical Biochemistry Biology Biochemistry Kruppel-Like Factor 4 Mice 03 medical and health sciences SOX2 Animals Humans Gene Regulatory Networks Epigenetics Induced pluripotent stem cell Molecular Biology Cell Proliferation Cellular Reprogramming Spermatogonia Up-Regulation Cell biology 030104 developmental biology Multipotent Stem Cell KLF4 Molecular Medicine Original Article Stem cell Reprogramming Transcription Factors |
| Zdroj: | Experimental & Molecular Medicine |
| ISSN: | 2092-6413 |
| Popis: | Spermatogonial stem cells (SSCs) are germline stem cells located along the basement membrane of seminiferous tubules in testes. Recently, SSCs were shown to be reprogrammed into multipotent SSCs (mSSCs). However, both the key factors and biological networks underlying this reprogramming remain elusive. Here, we present transcriptional regulatory networks (TRNs) that control cellular processes related to the SSC-to-mSSC reprogramming. Previously, we established intermediate SSCs (iSSCs) undergoing the transition to mSSCs and generated gene expression profiles of SSCs, iSSCs and mSSCs. By comparing these profiles, we identified 2643 genes that were up-regulated during the reprogramming process and 15 key transcription factors (TFs) that regulate these genes. Using the TF-target relationships, we developed TRNs describing how these TFs regulate three pluripotency-related processes (cell proliferation, stem cell maintenance and epigenetic regulation) during the reprogramming. The TRNs showed that 4 of the 15 TFs (Oct4/Pou5f1, Cux1, Zfp143 and E2f4) regulated cell proliferation during the early stages of reprogramming, whereas 11 TFs (Oct4/Pou5f1, Foxm1, Cux1, Zfp143, Trp53, E2f4, Esrrb, Nfyb, Nanog, Sox2 and Klf4) regulated the three pluripotency-related processes during the late stages of reprogramming. Our TRNs provide a model for the temporally coordinated transcriptional regulation of pluripotency-related processes during the SSC-to-mSSC reprogramming, which can be further tested in detailed functional studies. |
| Databáze: | OpenAIRE |
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