动物学研究, Год журнала: 2023, Номер 45(0), С. 1 - 2
Опубликована: Янв. 1, 2023
Язык: Английский
Cell stem cell, Год журнала: 2024, Номер 31(3), С. 312 - 333
Опубликована: Фев. 20, 2024
Though totipotency and pluripotency are transient during early embryogenesis, they establish the foundation for development of all mammals. Studying these in vivo has been challenging due to limited access ethical constraints, particularly humans. Recent progress led diverse culture adaptations epiblast cells vitro form totipotent pluripotent stem cells, which not only deepen our understanding embryonic but also serve as invaluable resources animal reproduction regenerative medicine. This review delves into hallmarks shedding light on their key molecular functional features.
Язык: Английский
Процитировано
31
Опубликована: Дек. 7, 2023
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Язык: Английский
Процитировано
30
Cell stem cell, Год журнала: 2025, Номер unknown
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
1
Cell stem cell, Год журнала: 2023, Номер 31(1), С. 127 - 147.e9
Опубликована: Дек. 22, 2023
Our understanding of pluripotency remains limited: iPSC generation has only been established for a few model species, pluripotent stem cell lines exhibit inconsistent developmental potential, and germline transmission demonstrated mice rats. By swapping structural elements between Sox2 Sox17, we built chimeric super-SOX factor, Sox2-17, that enhanced in five tested species: mouse, human, cynomolgus monkey, cow, pig. A swap alanine to valine at the interface Oct4 delivered gain function by stabilizing Sox2/Oct4 dimerization on DNA, enabling high-quality OSKM iPSCs capable supporting development healthy all-iPSC mice. emerged as core driver naive with its levels diminished upon priming. Transient overexpression SK cocktail (Sox+Klf4) restored boosted potential cells across providing universal method reset mammals.
Язык: Английский
Процитировано
22
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
Опубликована: Май 17, 2025
Pan-GSK3α/β inhibition promotes stem cell self-renewal through activation of WNT/β-catenin signaling, but its broad effects complicate the precise control states. Here, we show that selective GSK3α with BRD0705 supports long-term mouse embryonic cells (ESCs), epiblast (EpiSCs), and neural (NSCs), independent β-catenin signaling. When combined tankyrase inhibitor IWR1, broadly maintenance diverse pluripotent states, including ESCs, EpiSCs, formative cells. This BRD0705/IWR1 cocktail enables stable co-culture naive ESCs primed EpiSCs while preserving their distinct molecular functional identities. Single-cell transcriptomics, epigenomic profiling, assays confirm sustained lineage-specific features across types. These findings demonstrate enhances stemness by buffering against differentiation cues promoting intrinsic capacity. work identifies as a key regulator states establishes versatile culture system applications. Wang et al. Combined it NSCsBRD0705/IWR1 EpiSCsCo-cultured retain or identitiesBRD0705 preserves independently
Язык: Английский
Процитировано
1
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Март 6, 2024
ABSTRACT The crisis of biodiversity loss in the anthropogenic era requires new tools for studying non-model organisms. Elephants, example, are both an endangered species and excellent models complex phenotypes like size, social behavior, longevity, but they remain severely understudied. Here we report first derivation elephant ( Elephas maximus ) induced pluripotent stem cells (emiPSCs) achieved via a two-step process chemical-media induction colony selection, followed by overexpression transcription factors OCT4, SOX2, KLF4, MYC ± NANOG LIN28A , modulation TP53 pathway. Since seminal discovery reprogramming Shinya Yamanaka, iPSCs from many including functionally extinct northern white rhinocerous have been reported, emiPSCs remained elusive. While multiple protocol was adopted with little changes compared to model organisms mouse human, our emiPSC longer timeline inhibition expansion genes that hypothesized confer unique cancer resistance elephants. unlock tremendous potential explore cell fate determination, tissue development, therapies, drug screening, disease modeling, gametogenesis beyond further understanding this iconic megafauna. This study opens frontiers advanced organism cellular genetic rescue conservation.
Язык: Английский
Процитировано
4
Hepatic Medicine Evidence and Research, Год журнала: 2024, Номер Volume 16, С. 11 - 29
Опубликована: Фев. 1, 2024
Orthotopic liver transplantation (OLT) currently serves as the sole definitive treatment for thousands of patients suffering from end-stage disease; and existing supply donor livers OLT is drastically outpaced by increasing demand. To alleviate this significant gap in treatment, several experimental approaches have been devised with aim either offering interim support to waiting on transplant list or bioengineering complete infusing them fresh hepatic cells. Recently, interspecies blastocyst complementation has emerged a promising method generating organs utero over short timeframe. When coupled gene editing technology, it brought about potentially revolutionary transformation regenerative medicine. Blastocyst harbors notable potential human large animals, which could be used xenotransplantation humans, addressing scarcity OLT. Nevertheless, substantial ethical challenges still need overcome produce larger domestic animals like pigs. This review compiles current understanding outlines future possibilities humans.
Язык: Английский
Процитировано
3
Stem Cell Reports, Год журнала: 2025, Номер unknown, С. 102388 - 102388
Опубликована: Янв. 1, 2025
Highlights•Isolation of gpEpiSCs resembling E10.5–E11.5 epiblasts from embryos•gpEpiSC self-renewal depends on FGF2, ACTIVIN A, and WNT signaling inhibition•gpEpiSCs show transcriptional features the primed pluripotent stateSummaryGuinea pigs are valuable models for human disease research, yet lack established stem cell lines has limited their utility. In this study, we isolate characterize guinea pig epiblast cells (gpEpiSCs) post-implantation embryos. These differentiate into three germ layers, maintain normal karyotypes, rely FGF2 A pluripotency. Wingless/Integrated (WNT) inhibition is also essential maintenance. GpEpiSCs express key pluripotency markers (OCT4, SOX2, NANOG) share similarities with mouse cells. While many genes conserved between cells, analysis reveals species-specific differences in pluripotency-related pathways. Epigenetic highlights bivalent gene regulation, underscoring developmental potential. This work demonstrates both evolutionary conservation divergence providing a new tool biomedical research enhancing pigs' utility studying diseases.
Язык: Английский
Процитировано
0
Cell stem cell, Год журнала: 2025, Номер unknown
Опубликована: Фев. 1, 2025
Naive pluripotent stem cells (PSCs) are counterparts of early epiblast in the mammalian embryo. Mouse and human naive PSCs differ self-renewal requirements extraembryonic lineage potency. Here, we investigated generation chimpanzee PSCs. Colonies generated by resetting or reprogramming failed to propagate. We discovered that is enabled inhibition Polycomb repressive complex 2 (PRC2). Expanded show global transcriptome proximity embryo pre-implantation epiblast, with shared expression a subset pluripotency transcription factors. Chimpanzee can transition multilineage competence differentiate into trophectoderm hypoblast, forming tri-lineage blastoids. They thus provide higher primate comparative model for studying embryogenesis. Genetic deletions confirm PRC2 mediates growth arrest. Further, overcomes roadblock feeder-free propagation Therefore, excess deposition chromatin modification H3K27me3 an unexpected barrier PSC self-renewal.
Язык: Английский
Процитировано
0
Cell Reports, Год журнала: 2025, Номер 44(4), С. 115568 - 115568
Опубликована: Апрель 1, 2025
The specification of extra-embryonic mesenchyme (ExMC) is a prime example developmental divergence between mouse and human. Derived from definitive mesoderm during gastrulation, the human ExMC first appears at peri-implantation prior to gastrulation therefore its cellular origin, still unknown, must differ. In pluripotent stem cell model, we report that shares progenitor cells with trophoblast, suggesting trophectoderm origin. This ability form extend trophoblast lines. We define HAND1 as an essential regulator specification, null remaining in lineage. Bound by HAND1, ape-specific, endogenous retrovirus-derived LTR2B contributes unique features ExMC. Additionally, supports maintenance cells, possibly reflecting role maintaining epiblast pluripotency through development. Our data emphasize nascent evolutionary innovation early development provide system study this.
Язык: Английский
Процитировано
0