Human somatic cells subjected to genetic induction with six germ line-related factors display meiotic germ cell-like features

Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Martínez-Arroyo AM
- Míguez JM
- Moreno I
- Martínez S
- Quiñonero A
- Díaz-Gimeno P
- Marqués-Marí AI
- Remohí J
- Simón C
Grupos
Abstract
The in vitro derivation of human germ cells has attracted interest in the last years, but their direct conversion from human somatic cells has not yet been reported. Here we tested the ability of human male somatic cells to directly convert into a meiotic germ cell-like phenotype by inducing them with a combination of selected key germ cell developmental factors. We started with a pool of 12 candidates that were reduced to 6, demonstrating that ectopic expression of the germ line-related genes PRDM1, PRDM14, LIN28A, DAZL, VASA and SYCP3 induced direct conversion of somatic cells (hFSK (46, XY), and hMSC (46, XY)) into a germ cell-like phenotype in vitro. Induced germ cell-like cells showed a marked switch in their transcriptomic profile and expressed several post-meiotic germ line related markers, showed meiotic progression, evidence of epigenetic reprogramming, and approximately 1% were able to complete meiosis as demonstrated by their haploid status and the expression of several post-meiotic markers. Furthermore, xenotransplantation assays demonstrated that a subset of induced cells properly colonize the spermatogonial niche. Knowledge obtained from this work can be used to create in vitro models to study gamete-related diseases in humans.
Datos de la publicación
- ISSN/ISSNe:
- 2045-2322, 2045-2322
- Tipo:
- Article
- Páginas:
- 24956-24956
- DOI:
- 10.1038/srep24956
- Factor de Impacto:
- 1,692 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
SCIENTIFIC REPORTS NATURE PUBLISHING GROUP
Citas Recibidas en Web of Science: 15
Documentos
- No hay documentos
Filiaciones
Proyectos asociados
ESTUDIO DE LA ENFERMEDAD METASTASICA EN EL TEJIDO OVARICO CRIOPRESERVADO DE MUJERES CON CANCER DE MAMA
Investigador Principal: ANTONIO PELLICER MARTÍNEZ
PI08/90483 . INSTITUTO DE SALUD CARLOS III . 2009
CONTRATO POSTDOCTORAL DE INVESTIGACION SARA BORRELL
CD11/00292 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2012
CONTRATO POSTDOCTORAL DE INVESTIGACION SARA BORELL
CD12/00568 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2013
CONTRATO POST FSE (RIO HORTEGA)
CM13/00191 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2014
CONTRATO POSTDOCTORAL DE INVESTIGACION SARA BORRELL
Investigador Principal: ANTONIO PELLICER MARTÍNEZ
CD15/00058 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2016
TRAMIENTO COMBINADO DE VITAMINA D CON AGNRH SOBRE EL CRECIMIENTO DE LOS MIOMAS UTERINOS
Investigador Principal: ANTONIO PELLICER MARTÍNEZ
PI15/00312 . INSTITUTO DE SALUD CARLOS III . 2016
Cita
Medrano JV,Martínez AM,Míguez JM,Moreno I,Martínez S,Quiñonero A,Díaz P,Marqués AI,Pellicer A,Remohí J,Simón C. Human somatic cells subjected to genetic induction with six germ line-related factors display meiotic germ cell-like features. Sci Rep. 2016. 6. p. 24956-24956. IF:4,259. (1).