Domesticated cynomolgus monkey embryonic stem cells allow the generation of neonatal interspecies chimeric pigs.

Abstract:

:Blastocyst complementation by pluripotent stem cell (PSC) injection is believed to be the most promising method to generate xenogeneic organs. However, ethical issues prevent the study of human chimeras in the late embryonic stage of development. Primate embryonic stem cells (ESCs), which have similar pluripotency to human ESCs, are a good model for studying interspecies chimerism and organ generation. However, whether primate ESCs can be used in xenogenous grafts remains unclear. In this study, we evaluated the chimeric ability of cynomolgus monkey (Macaca fascicularis) ESCs (cmESCs) in pigs, which are excellent hosts because of their many similarities to humans. We report an optimized culture medium that enhanced the anti-apoptotic ability of cmESCs and improved the development of chimeric embryos, in which domesticated cmESCs (D-ESCs) injected into pig blastocysts differentiated into cells of all three germ layers. In addition, we obtained two neonatal interspecies chimeras, in which we observed tissue-specific D-ESC differentiation. Taken together, the results demonstrate the capability of D-ESCs to integrate and differentiate into functional cells in a porcine model, with a chimeric ratio of 0.001-0.0001 in different neonate tissues. We believe this work will facilitate future developments in xenogeneic organogenesis, bringing us one step closer to producing tissue-specific functional cells and organs in a large animal model through interspecies blastocyst complementation.

journal_name

Protein Cell

journal_title

Protein & cell

authors

Fu R,Yu D,Ren J,Li C,Wang J,Feng G,Wang X,Wan H,Li T,Wang L,Zhang Y,Hai T,Li W,Zhou Q

doi

10.1007/s13238-019-00676-8

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

97-107

issue

2

eissn

1674-800X

issn

1674-8018

pii

10.1007/s13238-019-00676-8

journal_volume

11

pub_type

杂志文章
  • The Fanconi anemia pathway and DNA interstrand cross-link repair.

    abstract::Fanconi anemia (FA) is an autosomal or X-linked recessive disorder characterized by chromosomal instability, bone marrow failure, cancer susceptibility, and a profound sensitivity to agents that produce DNA interstrand cross-link (ICL). To date, 15 genes have been identified that, when mutated, result in FA or an FA-l...

    journal_title:Protein & cell

    pub_type: 杂志文章,评审

    doi:10.1007/s13238-011-1098-y

    authors: Su X,Huang J

    更新日期:2011-09-01 00:00:00

  • Complement activation by phospholipids: the interplay of factor H and C1q.

    abstract::Complement proteins in blood recognize charged particles. The anionic phospholipid (aPL) cardiolipin binds both complement proteins C1q and factor H. C1q is an activator of the complement classical pathway, while factor H is an inhibitor of the alternative pathway. To examine opposing effects of C1q and factor H on co...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-010-0125-8

    authors: Tan LA,Yu B,Sim FC,Kishore U,Sim RB

    更新日期:2010-11-01 00:00:00

  • Integrative analysis of in vivo recording with single-cell RNA-seq data reveals molecular properties of light-sensitive neurons in mouse V1.

    abstract::Vision formation is classically based on projections from retinal ganglion cells (RGC) to the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). Neurons in the mouse V1 are tuned to light stimuli. Although the cellular information of the retina and the LGN has been widely studied, the transcriptome p...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-020-00720-y

    authors: Liu J,Wang M,Sun L,Pan NC,Zhang C,Zhang J,Zuo Z,He S,Wu Q,Wang X

    更新日期:2020-06-01 00:00:00

  • An inducible CRISPR-ON system for controllable gene activation in human pluripotent stem cells.

    abstract::Human pluripotent stem cells (hPSCs) are an important system to study early human development, model human diseases, and develop cell replacement therapies. However, genetic manipulation of hPSCs is challenging and a method to simultaneously activate multiple genomic sites in a controllable manner is sorely needed. He...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-016-0360-8

    authors: Guo J,Ma D,Huang R,Ming J,Ye M,Kee K,Xie Z,Na J

    更新日期:2017-05-01 00:00:00

  • Mutation analysis of large tumor suppressor genes LATS1 and LATS2 supports a tumor suppressor role in human cancer.

    abstract::In recent years, human cancer genome projects provide unprecedented opportunities for the discovery of cancer genes and signaling pathways that contribute to tumor development. While numerous gene mutations can be identified from each cancer genome, what these mutations mean for cancer is a challenging question to add...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-014-0122-4

    authors: Yu T,Bachman J,Lai ZC

    更新日期:2015-01-01 00:00:00

  • Proteomic identification and functional characterization of MYH9, Hsc70, and DNAJA1 as novel substrates of HDAC6 deacetylase activity.

    abstract::Histone deacetylase 6 (HDAC6), a predominantly cytoplasmic protein deacetylase, participates in a wide range of cellular processes through its deacetylase activity. However, the diverse functions of HDAC6 cannot be fully elucidated with its known substrates. In an attempt to explore the substrate diversity of HDAC6, w...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-014-0102-8

    authors: Zhang L,Liu S,Liu N,Zhang Y,Liu M,Li D,Seto E,Yao TP,Shui W,Zhou J

    更新日期:2015-01-01 00:00:00

  • Mechanism involved in the modulation of photoreceptor-specific cyclic nucleotidegated channel by the tyrosine kinase adapter protein Grb14.

    abstract::We recently found that growth factor receptor-bound (Grb) protein 14 is a novel physiological modulator of photoreceptor specific cyclic nucleotide-gated channel alpha subunit (CNGA1). Grb14 promotes the CNG channel closure through its Ras-associating (RA) domain. In the current study we show that this RA domain-media...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-011-1115-1

    authors: Gupta VK,Rajala A,Rodgers KK,Rajala RV

    更新日期:2011-11-01 00:00:00

  • Correction to: Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2.

    abstract::In the original publication the author's name 'Dimitri Lavillete' is published incorrectly. The correct author name should be spelt as 'Dimitri Lavillette' is provided in this correction. ...

    journal_title:Protein & cell

    pub_type: 已发布勘误

    doi:10.1007/s13238-020-00801-y

    authors: Xiong R,Zhang L,Li S,Sun Y,Ding M,Wang Y,Zhao Y,Wu Y,Shang W,Jiang X,Shan J,Shen Z,Tong Y,Xu L,Chen Y,Liu Y,Zou G,Lavillette D,Zhao Z,Wang R,Zhu L,Xiao G,Lan K,Li H,Xu K

    更新日期:2020-11-09 00:00:00

  • Inhibition of p53 and/or AKT as a new therapeutic approach specifically targeting ALT cancers.

    abstract::While the majority of all human cancers counteract telomere shortening by expressing telomerase, ~15% of all cancers maintain telomere length by a telomerase-independent mechanism known as alternative lengthening of telomeres (ALT). Here, we show that high load of intrinsic DNA damage is present in ALT cancer cells, l...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-019-0634-z

    authors: Ge Y,Wu S,Zhang Z,Li X,Li F,Yan S,Liu H,Huang J,Zhao Y

    更新日期:2019-11-01 00:00:00

  • Identification of arylamine N-acetyltransferase inhibitors as an approach towards novel anti-tuberculars.

    abstract::New anti-tubercular drugs and drug targets are urgently needed to reduce the time for treatment and also to identify agents that will be effective against Mycobacterium tuberculosis persisting intracellularly. Mycobacteria have a unique cell wall. Deletion of the gene for arylamine N-acetyltransferase (NAT) decreases ...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-010-0006-1

    authors: Westwood IM,Bhakta S,Russell AJ,Fullam E,Anderton MC,Kawamura A,Mulvaney AW,Vickers RJ,Bhowruth V,Besra GS,Lalvani A,Davies SG,Sim E

    更新日期:2010-01-01 00:00:00

  • IgG Fc engineering to modulate antibody effector functions.

    abstract::Therapeutic monoclonal antibodies are among the most effective biotherapeutics to date. An important aspect of antibodies is their ability to bind antigen while at the same time recruit immune effector functions. The majority of approved recombinant monoclonal antibody therapies are of the human IgG1 subclass, which c...

    journal_title:Protein & cell

    pub_type: 杂志文章,评审

    doi:10.1007/s13238-017-0473-8

    authors: Wang X,Mathieu M,Brezski RJ

    更新日期:2018-01-01 00:00:00

  • Structures of the N- and C-terminal domains of MHV-A59 nucleocapsid protein corroborate a conserved RNA-protein binding mechanism in coronavirus.

    abstract::Coronaviruses are the causative agent of respiratory and enteric diseases in animals and humans. One example is SARS, which caused a worldwide health threat in 2003. In coronaviruses, the structural protein N (nucleocapsid protein) associates with the viral RNA to form the filamentous nucleocapsid and plays a crucial ...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-010-0079-x

    authors: Ma Y,Tong X,Xu X,Li X,Lou Z,Rao Z

    更新日期:2010-07-01 00:00:00

  • Modeling CADASIL vascular pathologies with patient-derived induced pluripotent stem cells.

    abstract::Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary cerebrovascular disease caused by a NOTCH3 mutation. However, the underlying cellular and molecular mechanisms remain unidentified. Here, we generated non-integrative induced pluripotent stem cells...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-019-0608-1

    authors: Ling C,Liu Z,Song M,Zhang W,Wang S,Liu X,Ma S,Sun S,Fu L,Chu Q,Belmonte JCI,Wang Z,Qu J,Yuan Y,Liu GH

    更新日期:2019-04-01 00:00:00

  • The genetic and epigenetic alterations in human hepatocellular carcinoma: a recent update.

    abstract::Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies worldwide with very poor prognosis. It is generally accepted that the progression of HCC is a long-term process with accumulation of multiple genetic and epigenetic alterations, which further lead to the activation of critical oncogenes or i...

    journal_title:Protein & cell

    pub_type: 杂志文章,评审

    doi:10.1007/s13238-014-0065-9

    authors: Liu M,Jiang L,Guan XY

    更新日期:2014-09-01 00:00:00

  • Dscam mutation leads to hydrocephalus and decreased motor function.

    abstract::The nervous system is one of the most complicated organ systems in invertebrates and vertebrates. Down syndrome cell adhesion molecule (DSCAM) of the immunoglobulin (Ig) superfamily is expressed widely in the nervous system during embryonic development. Previous studies in Drosophila suggest that Dscam plays important...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-011-1072-8

    authors: Xu Y,Ye H,Shen Y,Xu Q,Zhu L,Liu J,Wu JY

    更新日期:2011-08-01 00:00:00

  • Transmembrane domain dependent inhibitory function of FcγRIIB.

    abstract::FcγRIIB, the only inhibitory IgG Fc receptor, functions to suppress the hyper-activation of immune cells. Numerous studies have illustrated its inhibitory function through the ITIM motif in the cytoplasmic tail of FcγRIIB. However, later studies revealed that in addition to the ITIM, the transmembrane (TM) domain of F...

    journal_title:Protein & cell

    pub_type: 杂志文章,评审

    doi:10.1007/s13238-018-0509-8

    authors: Wang J,Li Z,Xu L,Yang H,Liu W

    更新日期:2018-12-01 00:00:00

  • A novel xeno-free and feeder-cell-free system for human pluripotent stem cell culture.

    abstract::While human induced pluripotent stem cells (hiPSCs) have promising applications in regenerative medicine, most of the hiPSC lines available today are not suitable for clinical applications due to contamination with nonhuman materials, such as sialic acid, and potential pathogens from animal-product-containing cell cul...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-012-2002-0

    authors: Wang Q,Mou X,Cao H,Meng Q,Ma Y,Han P,Jiang J,Zhang H,Ma Y

    更新日期:2012-01-01 00:00:00

  • Expression of human FUS/TLS in yeast leads to protein aggregation and cytotoxicity, recapitulating key features of FUS proteinopathy.

    abstract::Mutations in the fused in sarcoma/translocated in liposarcoma (FUS/TLS) gene have been associated with amyotrophic lateral sclerosis (ALS). FUS-positive neuropathology is reported in a range of neurodegenerative diseases, including ALS and fronto-temporal lobar degeneration with ubiquitin-positive pathology (FTLDU). T...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-011-1014-5

    authors: Fushimi K,Long C,Jayaram N,Chen X,Li L,Wu JY

    更新日期:2011-02-01 00:00:00

  • Human pathogenic fungus Trichophyton schoenleinii activates the NLRP3 inflammasome.

    abstract::The fungus Trichophyton schoenleinii (T. schoenleinii) is the causative agent of Trichophytosis and Tinea favosa of the scalp in certain regions of Eurasia and Africa. Human innate immune system plays an important role in combating with various pathogens including fungi. The inflammasome is one of the most critical ar...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-013-2127-9

    authors: Li H,Wu S,Mao L,Lei G,Zhang L,Lu A,An L,Yang G,Abliz P,Meng G

    更新日期:2013-07-01 00:00:00

  • Human gut microbiota: the links with dementia development.

    abstract::Dementia is a comprehensive category of brain diseases that is great enough to affect a person's daily functioning. The most common type of dementia is Alzheimer's disease, which makes most of cases. New researches indicate that gastrointestinal tract microbiota are directly linked to dementia pathogenesis through tri...

    journal_title:Protein & cell

    pub_type: 杂志文章,评审

    doi:10.1007/s13238-016-0338-6

    authors: Alkasir R,Li J,Li X,Jin M,Zhu B

    更新日期:2017-02-01 00:00:00

  • MiR-29b suppresses the proliferation and migration of osteosarcoma cells by targeting CDK6.

    abstract::Osteosarcoma is the most common primary sarcoma of bone, and it is a leading cause of cancer death among adolescents and young adults. However, the molecular mechanism underlying osteosarcoma carcinogenesis remains poorly understood. Recently, cyclin-dependent kinase 6 (CDK6) was identified as an important oncogene. W...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-016-0277-2

    authors: Zhu K,Liu L,Zhang J,Wang Y,Liang H,Fan G,Jiang Z,Zhang CY,Chen X,Zhou G

    更新日期:2016-06-01 00:00:00

  • Structural dynamics of the yeast Shwachman-Diamond syndrome protein (Sdo1) on the ribosome and its implication in the 60S subunit maturation.

    abstract::The human Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease caused by mutations in a highly conserved ribosome assembly factor SBDS. The functional role of SBDS is to cooperate with another assembly factor, elongation factor 1-like (Efl1), to promote the release of eukaryotic initiation factor 6 (eIF6...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-015-0242-5

    authors: Ma C,Yan K,Tan D,Li N,Zhang Y,Yuan Y,Li Z,Dong MQ,Lei J,Gao N

    更新日期:2016-03-01 00:00:00

  • Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer.

    abstract::MTUS1 (microtubule-associated tumor suppressor 1) has been identified that can function as a tumor suppressor gene in many malignant tumors. However, the function and mechanisms underlying the regulation of MTUS1 are unclear. In the present study, we reported that miR-19a and miR-19b (miR-19a/b) promote proliferation ...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-017-0393-7

    authors: Gu Y,Liu S,Zhang X,Chen G,Liang H,Yu M,Liao Z,Zhou Y,Zhang CY,Wang T,Wang C,Zhang J,Chen X

    更新日期:2017-06-01 00:00:00

  • Crystal structure of a novel non-Pfam protein PF2046 solved using low resolution B-factor sharpening and multi-crystal averaging methods.

    abstract::Sometimes crystals cannot diffract X-rays beyond 3.0 Å resolution due to the intrinsic flexibility associated with the protein. Low resolution diffraction data not only pose a challenge to structure determination, but also hamper interpretation of mechanistic details. Crystals of a 25.6 kDa non-Pfam, hypothetical prot...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-010-0045-7

    authors: Su J,Li Y,Shaw N,Zhou W,Zhang M,Xu H,Wang BC,Liu ZJ

    更新日期:2010-05-01 00:00:00

  • Molecular mechanisms for survival regulation of chronic myeloid leukemia stem cells.

    abstract::Studies on chronic myeloid leukemia (CML) have served as a paradigm for cancer research and therapy. These studies involve the identification of the first cancer-associated chromosomal abnormality and the subsequent development of tyrosine kinase inhibitors (TKIs) that inhibit BCR-ABL kinase activity in CML. It become...

    journal_title:Protein & cell

    pub_type: 杂志文章,评审

    doi:10.1007/s13238-013-2115-0

    authors: Zhang H,Li S

    更新日期:2013-03-01 00:00:00

  • Correction to: A binding-block ion selective mechanism revealed by a Na/K selective channel.

    abstract::In the original publication the PDB numbers were not cited. ...

    journal_title:Protein & cell

    pub_type: 已发布勘误

    doi:10.1007/s13238-019-0619-y

    authors: Yu J,Zhang B,Zhang Y,Xu CQ,Zhuo W,Ge J,Li J,Gao N,Li Y,Yang M

    更新日期:2019-07-01 00:00:00

  • Overexpression of sigma-1 receptor inhibits ADAM10 and ADAM17 mediated shedding in vitro.

    abstract::The sigma-1 receptor is a molecular chaperone protein highly enriched in the brain. Recent studies linked it to many diseases, such as drug addition, Alzheimer's disease, stroke, depression, and even cancer. Sigma-1 receptor is enriched in lipid rafts, which are membrane microdomains essential in signaling processes. ...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-012-2006-9

    authors: Li J,Liu B,Gao X,Ma Z,CaoSong T,Mei YA,Zheng Y

    更新日期:2012-02-01 00:00:00

  • Formation and regulation of Yersinia biofilms.

    abstract::Flea-borne transmission is a recent evolutionary adaptation that distinguishes the deadly Yersinia pestis from its progenitor Y. Pseudotuberculosis, a mild pathogen transmitted via the food-borne route. Y. Pestis synthesizes biofilms in the flea gut, which is important for fleaborne transmission. Yersinia biofilms are...

    journal_title:Protein & cell

    pub_type: 杂志文章,评审

    doi:10.1007/s13238-011-1024-3

    authors: Zhou D,Yang R

    更新日期:2011-03-01 00:00:00

  • Identification of serotonin 2A receptor as a novel HCV entry factor by a chemical biology strategy.

    abstract::Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. Although several HCV protease/polymerase inhibitors were recently approved by U.S. FDA, the combination of antivirals targeting multiple processes of HCV lifecycle would optimize anti-HCV therapy and against potential drug-resistance. Viral entry i...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-018-0521-z

    authors: Cao L,Chen J,Wang Y,Yang Y,Qing J,Rao Z,Chen X,Lou Z

    更新日期:2019-03-01 00:00:00

  • Secreted miR-34a in astrocytic shedding vesicles enhanced the vulnerability of dopaminergic neurons to neurotoxins by targeting Bcl-2.

    abstract::MicroRNAs (miRNAs) are a class of noncoding RNAs that regulates target gene expression at posttranscriptional level, leading to further biological functions. We have demonstrated that microvesicles (MVs) can deliver miRNAs into target cells as a novel way of intercellular communication. It is reported that in central ...

    journal_title:Protein & cell

    pub_type: 杂志文章

    doi:10.1007/s13238-015-0168-y

    authors: Mao S,Sun Q,Xiao H,Zhang C,Li L

    更新日期:2015-07-01 00:00:00