Gastrulation is a key event in embryonic development when the germ layers are specified and the basic animal body plan is established. The complexities of primate gastrulation remain a mystery ...because of the difficulties in accessing primate embryos at this stage. Here, we report the establishment of an in vitro culture (IVC) system that supports the continuous development of cynomolgus monkey blastocysts beyond early gastrulation up to 20 days after fertilization. The IVC embryos highly recapitulated the key events of in vivo early postimplantation development, including segregation of the epiblast and hypoblast, formation of the amniotic and yolk sac cavities, appearance of the primordial germ cells, and establishment of the anterior-posterior axis. Single-cell RNA-sequencing analyses of the IVC embryos provide information about lineage specification during primate early postimplantation development. This system provides a platform with which to explore the characteristics and mechanisms of early postimplantation embryogenesis in primates with possible conservation of cell movements and lineages in human embryogenesis.
Breast cancer amplified sequence 2 (BCAS2) is involved in multiple biological processes, including pre-mRNA splicing. However, the physiological roles of BCAS2 are still largely unclear. Here we ...report that BCAS2 is specifically enriched in spermatogonia of mouse testes. Conditional disruption of Bcas2 in male germ cells impairs spermatogenesis and leads to male mouse infertility. Although the spermatogonia appear grossly normal, spermatocytes in meiosis prophase I and meiosis events (recombination and synapsis) are rarely observed in the BCAS2-depleted testis. In BCAS2 null testis, 245 genes are altered in alternative splicing forms; at least three spermatogenesis-related genes (Dazl, Ehmt2 and Hmga1) can be verified. In addition, disruption of Bcas2 results in a significant decrease of the full-length form and an increase of the short form (lacking exon 8) of DAZL protein. Altogether, our results suggest that BCAS2 regulates alternative splicing in spermatogonia and the transition to meiosis initiation, and male fertility.
Maintaining genomic stability is crucial for embryonic stem cells (ESCs). ESCs with unrepaired DNA damage are eliminated through differentiation and apoptosis. To date, only tumor suppressor p53 is ...known to be implicated in this quality control process. Here, we identified a p53-independent quality control factor lncRNA NONMMUT028956 (
for short) in mouse ESCs.
is prevalently expressed in ESCs and regulates the differentiation of ESCs after DNA damage. Mechanistically, Ataxia telangiectasia mutated (ATM) activation drives m
A methylation of
, which promotes its interaction with Krüppel-like factor 4 (KLF4).
-KLF4 association sequestrates the KLF4 protein and prevents KLF4's transcriptional regulation on pluripotency. This posttranslational mechanism favors the rapid shutdown of the regulatory circuitry of pluripotency. Thus, ATM signaling in ESCs can activate two pathways mediated by p53 and
, respectively, which act together to ensure robust differentiation and apoptosis in response to unrepaired DNA damage.
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