In Vitro Derivation and Propagation of Spermatogonial Stem Cell Activity from Mouse Pluripotent Stem Cells.

نویسندگان

  • Yukiko Ishikura
  • Yukihiro Yabuta
  • Hiroshi Ohta
  • Katsuhiko Hayashi
  • Tomonori Nakamura
  • Ikuhiro Okamoto
  • Takuya Yamamoto
  • Kazuki Kurimoto
  • Kenjiro Shirane
  • Hiroyuki Sasaki
  • Mitinori Saitou
چکیده

The in vitro derivation and propagation of spermatogonial stem cells (SSCs) from pluripotent stem cells (PSCs) is a key goal in reproductive science. We show here that when aggregated with embryonic testicular somatic cells (reconstituted testes), primordial germ cell-like cells (PGCLCs) induced from mouse embryonic stem cells differentiate into spermatogonia-like cells in vitro and are expandable as cells that resemble germline stem cells (GSCs), a primary cell line with SSC activity. Remarkably, GSC-like cells (GSCLCs), but not PGCLCs, colonize adult testes and, albeit less effectively than GSCs, contribute to spermatogenesis and fertile offspring. Whole-genome analyses reveal that GSCLCs exhibit aberrant methylation at vulnerable regulatory elements, including those critical for spermatogenesis, which may restrain their spermatogenic potential. Our study establishes a strategy for the in vitro derivation of SSC activity from PSCs, which, we propose, relies on faithful epigenomic regulation.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

O-3: Identification and Characterization of Repopulating Spermatogonial Stem Cells from The Adult Human Testis

Background: This study was conducted to identify and characterize repopulating spermatogonial stem cells (SSCs) in the adult human testes. Materials and Methods: Testes biopsies from obstructive azoospermic patients and normal segments of human testicular tissue were used. Flow cytometry, real time PCR and immunohistochemical analysis were performed. Purified human spermatogonia were transplant...

متن کامل

P-50: Elongating and Elongated Spermatids Manufactured In Vitro from Non-Human Primate Pluripotent Stem Cells

Background: We have recently shown that human embryonic (hESCs) and induced pluripotent stem cells (hiPSCs) can differentiate into advanced spermatogenic cells including round spermatids by in vitro culture (Easley et al., Direct differentiation of human pluripotent stem cells into haploid spermatogenic cells. Cell Reports 2, 440-446 2012) and also, in collaboration, that rhesus spermatogonial ...

متن کامل

Evaluation and Comparison of the Expression Levels of the ZBTB16 (Plzf) and ZFP Genes and Alkaline Phosphatase in Three Cell Populations: Mouse Spermatogonial Stem Cells, Embryonic Stem-Like Cells (Es-Like), And Embryonic Stem Cells

Introduction: One of the vital enzymes during spermatogenesis, which is one of the pluripotency factors of stem cells and contributes to maintaining their pluripotency is alkaline phosphatase. ZBTB16 and ZFP proteins are critical elements in stem cells which are expressed in pluripotent stem cells and maintain their pluripotency due to their role in messaging pathways. Material & Methods: The ...

متن کامل

I-54: New Models for Human and Mouse Genetic

The possibility to reprogram somatic human cells will greatly and deeply change genetic approach and allow the development of new tools to study genetics diseases. Indeed, our ability to study human genetic diseases suffers from the lack of valid in vitro models. The latter should (i) be originating from human primary cells, (ii) be able to self-renew for a long time and (iii) be able to differ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Cell reports

دوره 17 10  شماره 

صفحات  -

تاریخ انتشار 2016