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Transcriptional regulatory networks underlying the reprogramming of spermatogonial stem cells to multipotent stem cells

Title
Transcriptional regulatory networks underlying the reprogramming of spermatogonial stem cells to multipotent stem cells
Authors
Jeong, Hoe-SuBhin, JinhyukKim, Hyung JoonHwang, DaeheeLee, Dong RyulKim, Kye-Seong
DGIST Authors
Hwang, Daehee
Issue Date
2017-04
Citation
Experimental and Molecular Medicine, 49
Type
Article
Article Type
Article
Keywords
Adult Human TestisBiologyGenerationMolecular Interaction DatabaseMouse TestisPluripotencySelf RenewalSomatic CellsTransfer RNA SynthetasesTumorigenicity
ISSN
1226-3613
Abstract
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.
URI
http://hdl.handle.net/20.500.11750/4209
DOI
10.1038/emm.2017.2
Publisher
NATURE PUBLISHING GROUP
Related Researcher
  • Author Hwang, Dae Hee Systems Biology and Medicine Lab
  • Research Interests Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
Files:
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Collection:
New BiologyETC1. Journal Articles
ETC1. Journal Articles


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