TY - JOUR
T1 - Testicular somatic cell-like cells derived from embryonic stem cells induce differentiation of epiblasts into germ cells
AU - Rore, Holly
AU - Owen, Nicholas
AU - Piña-Aguilar, Raul Eduardo
AU - Docherty, Kevin
AU - Sekido, Ryohei
N1 - Funding Information:
We thank Dr Robin Lovell-Badge and Prof Azim Surani for tesco-cfp ESC line and Prdm1-gfp ESC line, respectively. We also thank the University of Aberdeen Microscopy, Histology and real-time PCR facilities as well as the Iain Fraser Cytometry Centre for training and use of their equipment. H.R. was supported by BBSRC EASTBIO doctoral training partnership (#RG10147-10). This research was supported by grants from NHS Grampian (#RGB4407) and Royal Society (#RG12667-10).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/6/28
Y1 - 2021/6/28
N2 - Regeneration of the testis from pluripotent stem cells is a real challenge, reflecting the complexity of the interaction of germ cells and somatic cells. Here we report the generation of testicular somatic cell-like cells (TesLCs) including Sertoli cell-like cells (SCLCs) from mouse embryonic stem cells (ESCs) in xeno-free culture. We find that Nr5a1/SF1 is critical for interaction between SCLCs and PGCLCs. Intriguingly, co-culture of TesLCs with epiblast-like cells (EpiLCs), rather than PGCLCs, results in self-organised aggregates, or testicular organoids. In the organoid, EpiLCs differentiate into PGCLCs or gonocyte-like cells that are enclosed within a seminiferous tubule-like structure composed of SCLCs. Furthermore, conditioned medium prepared from TesLCs has a robust inducible activity to differentiate EpiLCs into PGCLCs. Our results demonstrate conditions for in vitro reconstitution of a testicular environment from ESCs and provide further insights into the generation of sperm entirely in xeno-free culture.
AB - Regeneration of the testis from pluripotent stem cells is a real challenge, reflecting the complexity of the interaction of germ cells and somatic cells. Here we report the generation of testicular somatic cell-like cells (TesLCs) including Sertoli cell-like cells (SCLCs) from mouse embryonic stem cells (ESCs) in xeno-free culture. We find that Nr5a1/SF1 is critical for interaction between SCLCs and PGCLCs. Intriguingly, co-culture of TesLCs with epiblast-like cells (EpiLCs), rather than PGCLCs, results in self-organised aggregates, or testicular organoids. In the organoid, EpiLCs differentiate into PGCLCs or gonocyte-like cells that are enclosed within a seminiferous tubule-like structure composed of SCLCs. Furthermore, conditioned medium prepared from TesLCs has a robust inducible activity to differentiate EpiLCs into PGCLCs. Our results demonstrate conditions for in vitro reconstitution of a testicular environment from ESCs and provide further insights into the generation of sperm entirely in xeno-free culture.
KW - UKRI
KW - BBSRC
UR - http://www.scopus.com/inward/record.url?scp=85108828566&partnerID=8YFLogxK
UR - https://abdn.pure.elsevier.com/en/
U2 - 10.1038/s42003-021-02322-8
DO - 10.1038/s42003-021-02322-8
M3 - Article
C2 - 34183774
AN - SCOPUS:85108828566
SN - 2399-3642
VL - 4
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 802
ER -