Musashi1 and its short C-terminal variants regulate pluripotency states in embryonic stem cells DOI Open Access
Youwei Chen, Hailin Zhang, Jiazhen Han

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Май 7, 2022

ABSTRACT Musashi1 (MSI1) is a marker for adult stem cells, but little known its expression and function in pluripotent cells (PSCs). Here we report that MSI1 expressed embryonic (ESCs) required pluripotency maintenance. We found there exit short c-terminal variants (MSI1-C, hMSI1 272-362 or mMSI1 138-362 ) naïve not primed ESCs. When overexpressed, MSI1-C facilitate primed-to-naïve transition by elevating the of hESCs toward formative-like state, enable better survival human-mouse interspecies cell completion, enhance ability blastoid formation after induction. Mechanistically, show variants, though lacking RNA recognition motifs, bind to RNAs, stress resistance upregulate DNA damage repair genes. Thus, this study demonstrates ESCs utilize newly identified proteins as double swords regulate states.

Язык: Английский

Protocols for the application of human embryonic stem cell-derived neurons for aging modeling and gene manipulation DOI Creative Commons
Hui Zhang, Shuhui Sun, Juan Carlos Izpisúa Belmonte

и другие.

STAR Protocols, Год журнала: 2025, Номер 6(1), С. 103633 - 103633

Опубликована: Фев. 10, 2025

Язык: Английский

Процитировано

0
Towards human organ generation using interspecies blastocyst complementation: Challenges and perspectives for therapy DOI Creative Commons
Hemanta Sarmah, Anri Sawada, Youngmin Hwang

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Янв. 19, 2023

Millions of people suffer from end-stage refractory diseases. The ideal treatment option for terminally ill patients is organ transplantation. However, donor organs are in absolute shortage, and sadly, most die while waiting a organ. To date, no technology has achieved long-term sustainable patient-derived generation. In this regard, emerging technologies chimeric human production

Язык: Английский

Процитировано

9
RNA Sensing and Innate Immunity Constitutes a Barrier for Interspecies Chimerism DOI Creative Commons
Yingying Hu, Hai‐Xi Sun, Masahiro Sakurai

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Март 9, 2023

Abstract Interspecies chimera formation with human pluripotent stem cells (PSCs) holds great promise to generate humanized animal models and provide donor organs for transplant. However, the approach is currently limited by low levels of ultimately represented in chimeric embryos. Different strategies have been developed improve chimerism genetically editing PSCs. To date, however, it remains unexplored if can be enhanced animals through modifying host Leveraging interspecies PSC competition model, here we discovered retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling, an RNA sensor, “winner” plays important role competitive interactions between co-cultured mouse We found that genetic inactivation Ddx58/Ifih1-Mavs-Irf7 axis compromised status PSCs their ability outcompete from evolutionarily distant species during co-culture. Furthermore, using Mavs -deficient embryos substantially improved unmodified cell survival. Comparative transcriptome analyses based on species-specific sequences suggest contact-dependent human-to-mouse transfer RNAs likely a part mediating cross-species interactions. Taken together, these findings establish previously unrecognized sensing innate immunity provides proof-of-concept embryos, rather than PSCs, enhance chimerism.

Язык: Английский

Процитировано

6
Advancements in medical research using fetal sheep: Implications for human health and treatment methods DOI
Tomoyuki Abe, Borjigin Sarentonglaga, Yoshikazu Nagao

и другие.

Animal Science Journal, Год журнала: 2024, Номер 95(1)

Опубликована: Янв. 1, 2024

Abstract Sheep are typically considered as industrial animals that provide wool and meals. However, they play a significant role in medical research addition to their conventional use. Notably, sheep fetuses resistant surgical invasions can endure numerous manipulations, such needle puncture cell transplantation, operations requiring exposure beyond the uterus. Based on these distinguishing characteristics, we established chimeric model capable of producing human/monkey pluripotent cell‐derived blood cells via fetal liver. Furthermore, have become crucial human models, acting platforms for developing improving techniques intrauterine surgery address congenital disorders clarifying complex pharmacokinetic interactions between mothers fetuses. This study emphasizes contributions advancing disease understanding treatment strategies, highlighting unique characteristics not present other animals.

Язык: Английский

Процитировано

1
A new paradigm for generating high-quality cardiac pacemaker cells from mouse pluripotent stem cells DOI Creative Commons

Zheyi Lin,

Bowen Lin,

Chengwen Hang

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Сен. 6, 2024

Язык: Английский

Процитировано

1
Mechanisms and strategies to promote cardiac xenotransplantation DOI Creative Commons
Daniel J. Garry, Joshua Weiner, Sarah M. Greising

и другие.

Journal of Molecular and Cellular Cardiology, Год журнала: 2022, Номер 172, С. 109 - 119

Опубликована: Авг. 27, 2022

Язык: Английский

Процитировано

6
Long-term in vivo chimeric cells tracking in non-human primate DOI Creative Commons
Junmo Wu, Yu Kang, Xiang Luo

и другие.

Protein & Cell, Год журнала: 2023, Номер 15(3), С. 207 - 222

Опубликована: Сен. 27, 2023

Abstract Non-human primates (NHPs) are increasingly used in preclinical trials to test the safety and efficacy of biotechnology therapies. Nonetheless, given ethical issues costs associated with this model, it would be highly advantageous use NHP cellular models clinical studies. However, developing maintaining naïve state primate pluripotent stem cells (PSCs) remains difficult as does vivo detection PSCs, thus limiting application cynomolgus monkey. Here, we report a chemically defined, xeno-free culture system for culturing deriving monkey PSCs vitro. The display global gene expression genome-wide hypomethylation patterns distinct from monkey-primed cells. We also found signaling pathways components that may increase potential chimera formation. Crucially biomedical applications, were able integrate bioluminescent reporter genes into track them chimeric embryos engineered retained embryonic extra-embryonic developmental potential. Meanwhile, generated carrying cells, which more than 2 years living animals. Our study could have broad utility cell engineering utilizing

Язык: Английский

Процитировано

3
Derivation of Arbas Cashmere Goat Induced Pluripotent Stem Cells in LCDM with Trophectoderm Lineage Differentiation and Interspecies Chimeric Abilities DOI Open Access
Fang Liu, Jing Wang, Yongli Yue

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(19), С. 14728 - 14728

Опубликована: Сен. 29, 2023

The Arbas cashmere goat is a unique biological resource that plays vital role in livestock husbandry China. LCDM medium with special small molecules (consisting of human LIF, CHIR99021, (S)-(+)-dimethindene maleate, and minocycline hydrochloride) for generation pluripotent stem cells (PSCs) bidirectional developmental potential mice, humans, pigs, bovines. However, there no report on whether can support PSCs the same ability goats. In this study, we applied to generate induced (giPSCs) from fetal fibroblasts (GFFs) by reprogramming. derived giPSCs exhibited cell morphology, expressing markers, could differentiate into three germ layers. Moreover, differentiated trophectoderm lineage spontaneous directed differentiation vitro. contributed embryonic extraembryonic tissue preimplantation blastocysts postimplantation chimeric embryos. RNA-sequencing analysis showed were very close embryos at blastocyst stage have similar properties typical extended (EPSCs). establishment provides new way domestic animals lays foundation basic research biology agriculture.

Язык: Английский

Процитировано

3
Short C-terminal Musashi-1 proteins regulate pluripotency states in embryonic stem cells DOI Creative Commons
Youwei Chen, Ying Chen,

Qianyan Li

и другие.

Cell Reports, Год журнала: 2023, Номер 42(10), С. 113308 - 113308

Опубликована: Окт. 1, 2023

The RNA-binding protein Musashi-1 (MSI1) regulates the proliferation and differentiation of adult stem cells. However, its role in embryonic cells (ESCs) early development remains poorly understood. Here, we report presence short C-terminal MSI1 (MSI1-C) proteins mouse embryos ESCs, but not human under conventional culture conditions. In mESCs, deletion MSI1-C together with full-length causes developmental arrest pluripotency dissolution. is induced upon naive induction facilitates hESC acquisition, elevating primed hESCs toward a formative-like state. are nuclear localized bind to RNAs involved DNA-damage repair (including MLH1, BRCA1, MSH2), conferring on better survival human-mouse interspecies cell competition prolonged ability form blastoids. This study identifies as an essential regulator ESC states development.

Язык: Английский

Процитировано

2
Producing human livers from human stem cells via blastocyst complementation DOI Creative Commons
Boyukkhanim Ahmadzada, Philipp Felgendreff,

Anna M. Minshew

и другие.

Current Opinion in Biomedical Engineering, Год журнала: 2024, Номер 31, С. 100537 - 100537

Опубликована: Май 16, 2024

The need for organ transplants exceeds donor availability. In the quest to solve this shortage, most remarkable area of advancement is production through use chimeric embryos, commonly known as blastocyst complementation. This technique involves combination different species generate chimeras, where extent cell contribution desired tissue or can be regulated. However, ethical concerns arise with brain in such chimeras. Furthermore, ratio contributed cells host animal system low chimeras associated apoptosis. review discusses latest innovations complementation and highlights progress made creating organs transplant.

Язык: Английский

Процитировано

0