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Induction of Sertoli-like cells from human fibroblasts by NR5A1 and GATA4.
- Source :
-
ELife [Elife] 2019 Nov 11; Vol. 8. Date of Electronic Publication: 2019 Nov 11. - Publication Year :
- 2019
-
Abstract
- Sertoli cells are essential nurse cells in the testis that regulate the process of spermatogenesis and establish the immune-privileged environment of the blood-testis-barrier (BTB). Here, we report the in vitro reprogramming of fibroblasts to human induced Sertoli-like cells (hiSCs). Initially, five transcriptional factors and a gene reporter carrying the AMH promoter were utilized to obtain the hiSCs. We further reduce the number of reprogramming factors to two, NR5A1 and GATA4, and show that these hiSCs have transcriptome profiles and cellular properties that are similar to those of primary human Sertoli cells. Moreover, hiSCs can sustain the viability of spermatogonia cells harvested from mouse seminiferous tubules. hiSCs suppress the proliferation of human T lymphocytes and protect xenotransplanted human cells in mice with normal immune systems. hiSCs also allow us to determine a gene associated with Sertoli cell only syndrome (SCO), CX43, is indeed important in regulating the maturation of Sertoli cells.<br />Competing Interests: JL, NW, JH, JD, YG, LL, WW, CY, ZL, KK No competing interests declared<br /> (© 2019, Liang et al.)
- Subjects :
- Animals
Cell Differentiation genetics
Cell Proliferation
Coculture Techniques
Fibroblasts cytology
GATA4 Transcription Factor metabolism
Gene Expression Regulation, Developmental
Humans
Male
Mice
Promoter Regions, Genetic
Receptors, Peptide genetics
Receptors, Peptide metabolism
Receptors, Transforming Growth Factor beta genetics
Receptors, Transforming Growth Factor beta metabolism
SOX9 Transcription Factor genetics
SOX9 Transcription Factor metabolism
Seminiferous Tubules cytology
Seminiferous Tubules growth & development
Seminiferous Tubules metabolism
Sertoli Cell-Only Syndrome metabolism
Sertoli Cell-Only Syndrome pathology
Sertoli Cells cytology
Sertoli Cells transplantation
Spermatogenesis genetics
Spermatogonia cytology
Spermatogonia growth & development
Spermatogonia metabolism
Steroidogenic Factor 1 metabolism
T-Lymphocytes cytology
T-Lymphocytes metabolism
Transcription Factors genetics
Transcription Factors metabolism
Transplantation, Heterologous methods
WT1 Proteins genetics
WT1 Proteins metabolism
Cellular Reprogramming
Fibroblasts metabolism
GATA4 Transcription Factor genetics
Sertoli Cell-Only Syndrome genetics
Sertoli Cells metabolism
Steroidogenic Factor 1 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 31710289
- Full Text :
- https://doi.org/10.7554/eLife.48767