Inhibition of ERK1/2 prevents neural and mesendodermal differentiation and promotes human embryonic stem cell self-renewal.

Abstract:

:Extracellular signal-regulated kinases (ERKs) have many important functions during embryogenesis. However, their role in embryonic stem (ES) cells is controversial. Previous studies reported that, in contrast to mouse ES cells, human ES cells differentiate if ERK1/2 is inhibited. We reexamined the role of ERK1/2 in human ES cells using a chemically defined culture system and found that when ERK1/2 is blocked with specific chemical inhibitors, neural and mesendodermal differentiation is prevented, but cells become sensitive to BMP-induced differentiation. Inhibition of ERK1/2 significantly reduced the clonogenicity of human ES cells by preventing cell adhesion and survival. When this negative effect was avoided, we were able to maintain human ES cell self-renewal for more than 3months in the presence of ERK1/2 inhibitors in a chemically defined culture system containing FGF2 and activin A but no BMP4. Our results suggest that the functional outcome of FGF/ERK1/2 signaling in human ES cells is influenced by the relative levels of activin A/TGFbeta and BMP activity. Moreover, activation of ERK1/2 in human ES cells is required for proper neural and mesendodermal differentiation. In contrast to mouse ES cells, a low level of BMP4 is sufficient to initiate extraembryonic differentiation when ERK1/2 is inhibited.

journal_name

Stem Cell Res

journal_title

Stem cell research

authors

Na J,Furue MK,Andrews PW

doi

10.1016/j.scr.2010.06.002

subject

Has Abstract

pub_date

2010-09-01 00:00:00

pages

157-69

issue

2

eissn

1873-5061

issn

1876-7753

pii

S1873-5061(10)00073-5

journal_volume

5

pub_type

杂志文章
  • Lymphoblast-derived integration-free iPSC lines from a female and male Alzheimer's disease patient expressing different copy numbers of a coding CNV in the Alzheimer risk gene CR1.

    abstract::Human lymphoblast cells from a female and male patient diagnosed with Alzheimer's disease (AD) with different genotypes of a functional copy number variation (CNV) in the AD risk gene CR1 were used to generate integration-free induced pluripotent stem cells (iPSCs) employing episomal plasmids expressing OCT4, SOX2, NA...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2016.10.003

    authors: Schröter F,Sleegers K,Van Cauwenberghe C,Bohndorf M,Wruck W,Van Broeckhoven C,Adjaye J

    更新日期:2016-11-01 00:00:00

  • Generation of two control iPSC clones NCCSi008-A and NCCSi008-B from an individual of Indian ethnicity.

    abstract::Two iPSC clones, NCCSi008-A and NCCSi008-B, were generated from a healthy male individual of Indian origin by reprogramming his CD4+ T cells with an integration free Sendai viral vector. The established iPSC clones showed high alkaline phosphatase (ALP) activity, expression of pluripotency markers, a normal male karyo...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2020.101765

    authors: Vaidyanath A,Khan M,Shiras A

    更新日期:2020-05-01 00:00:00

  • CD71(high) population represents primitive erythroblasts derived from mouse embryonic stem cells.

    abstract::The CD71/Ter119 combination has been widely used to reflect dynamic maturation of erythrocytes in vivo. However, because CD71 is expressed on all proliferating cells, it is unclear whether it can be utilized as an erythrocyte-specific marker during differentiation of embryonic stem cells (ESCs). In this study, we reve...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2014.11.002

    authors: Chao R,Gong X,Wang L,Wang P,Wang Y

    更新日期:2015-01-01 00:00:00

  • Generation of a heterozygous C-peptide-mCherry reporter human iPSC line (HMGUi001-A-8).

    abstract::The peptide hormone insulin produced by pancreatic β-cells undergoes post-transcriptional processing before secretion. In particular, C-peptide is cleaved from pro-insulin to generate mature insulin. Here, we introduce a C-peptide-mCherry human iPSC line (HMGUi001-A-8). The line was generated by CRISPR/Cas9 mediated h...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2020.102126

    authors: Siehler J,Blöchinger AK,Akgün M,Wang X,Shahryari A,Geerlof A,Lickert H,Burtscher I

    更新日期:2020-12-16 00:00:00

  • Establishment of induced pluripotent stem cell line (GSPHi001-A) from a 6-year old female with nephrotic syndrome.

    abstract::Peripheral blood mononuclear cells (PBMCs) were collected from a 6-year-old female child who was clinically diagnosed as primary nephrotic syndrome (NS) with hormone resistance. An iPSC line was successfully established by the Sendai-virus (SeV) delivery system. The iPS-19 (GSPHi001-A) expressed pluripotent markers, e...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2019.101661

    authors: Gao X,Gao X,Zhao H,Cui W,Tan M,Deng H

    更新日期:2019-12-01 00:00:00

  • Promotion of hematopoietic differentiation from mouse induced pluripotent stem cells by transient HoxB4 transduction.

    abstract::Ectopic expression of HoxB4 in embryonic stem (ES) cells leads to an efficient production of hematopoietic cells, including hematopoietic stem/progenitor cells. Previous studies have utilized a constitutive HoxB4 expression system or tetracycline-regulated HoxB4 expression system to induce hematopoietic cells from ES ...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2011.09.001

    authors: Tashiro K,Kawabata K,Omori M,Yamaguchi T,Sakurai F,Katayama K,Hayakawa T,Mizuguchi H

    更新日期:2012-03-01 00:00:00

  • Generation of three iPSC lines (IAIi002, IAIi004, IAIi003) from Rubinstein-Taybi syndrome 1 patients carrying CREBBP non sense c.4435G>T, p.(Gly1479*) and c.3474G>A, p.(Trp1158*) and missense c.4627G>T, p.(Asp1543Tyr) mutations.

    abstract::Rubinstein-Taybi syndrome (RSTS) is a neurodevelopmental disorder characterized by growth retardation, skeletal anomalies and intellectual disability, caused by heterozygous mutations in either CREBBP (RSTS1) or EP300 (RSTS2) genes. We characterized 3 iPSC lines generated by Sendai from blood of RSTS1 patients with un...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2019.101553

    authors: Alari V,Russo S,Rovina D,Garzo M,Crippa M,Calzari L,Scalera C,Concolino D,Castiglioni E,Giardino D,Prosperi E,Finelli P,Gervasini C,Gowran A,Larizza L

    更新日期:2019-10-01 00:00:00

  • Human embryonic stem cells and derived contractile embryoid bodies are susceptible to Coxsakievirus B infection and respond to interferon Iβ treatment.

    abstract::We studied the susceptibility of human embryonic stem cells and derived contractile embryoid bodies from WAO9, HUES-5 and HUES-16 cell lines to Coxsackievirus B infection. After validating stem cell-like properties and cardiac phenotype, Coxsackievirus B receptors CAR and DAF, as well as type I interferon receptors we...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2010.09.002

    authors: Scassa ME,Jaquenod de Giusti C,Questa M,Pretre G,Richardson GA,Bluguermann C,Romorini L,Ferrer MF,Sevlever GE,Miriuka SG,Gómez RM

    更新日期:2011-01-01 00:00:00

  • uPAR and cathepsin B-mediated compartmentalization of JNK regulates the migration of glioma-initiating cells.

    abstract::In the present study, we investigated the effect of simultaneous downregulation of uPAR and cathepsin B (pUC), alone or in combination with radiation, on JNK-MAPK signaling pathway in regulating the migration of non-GICs (glioma-initiating cells) and GICs. The increase in the expression of p-JNK with pUC treatment was...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2014.02.008

    authors: Alapati K,Kesanakurti D,Rao JS,Dasari VR

    更新日期:2014-05-01 00:00:00

  • Knockdown of SVCT2 impairs in-vitro cell attachment, migration and wound healing in bone marrow stromal cells.

    abstract::Bone marrow stromal cell (BMSC) adhesion and migration are fundamental to a number of pathophysiologic processes, including fracture and wound healing. Vitamin C is beneficial for bone formation, fracture repair and wound healing. However, the role of the vitamin C transporter in BMSC adhesion, migration and wound hea...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2013.11.002

    authors: Sangani R,Pandya CD,Bhattacharyya MH,Periyasamy-Thandavan S,Chutkan N,Markand S,Hill WD,Hamrick M,Isales C,Fulzele S

    更新日期:2014-03-01 00:00:00

  • Derivation of hybrid ES cell lines from two different strains of mice.

    abstract::Parental origin-dependent expression of the imprinted genes is essential for mammalian development. Zfp57 maintains genomic imprinting in mouse embryos and ES cells. To examine the allelic expression patterns of the imprinted genes in ES cells, we obtained multiple hybrid ES clones that were directly derived from the ...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2016.01.017

    authors: Lau HT,Liu L,Ray C,Bell FT,Li X

    更新日期:2016-03-01 00:00:00

  • Generating an MEIS1 homozygous knockout human embryonic stem cell line using the CRISPR/Cas9 system.

    abstract::Myeloid ecotropic viral integration site 1 (MEIS1) plays an essential role in the development of several embryonic organs, such as the central nervous system and eyes. To further investigate the role of MEIS1 in embryonic development, herein, we generated a MEIS1 homozygous knockout human embryonic stem cell (hESC) li...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2020.102069

    authors: Zhang C,Yu Y,Li F,Lan X,Wang L

    更新日期:2020-12-01 00:00:00

  • SOX4 inhibits oligodendrocyte differentiation of embryonic neural stem cells in vitro by inducing Hes5 expression.

    abstract::SOX4 has been shown to promote neuronal differentiation both in the adult and embryonic neural progenitors. Ectopic SOX4 expression has also been shown to inhibit oligodendrocyte differentiation in mice, however the underlying molecular mechanisms remain poorly understood. Here we demonstrate that SOX4 regulates trans...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2018.10.005

    authors: Braccioli L,Vervoort SJ,Puma G,Nijboer CH,Coffer PJ

    更新日期:2018-12-01 00:00:00

  • Generation of human induced pluripotent stem cell (iPSC) line from an unaffected female carrier of mutation in SACSIN gene.

    abstract::The human iPSC cell line, CARS-FiPS4F1 (ESi064-A), derived from dermal fibroblast from the apparently healthy carrier of the mutation of the gene SACSIN, was generated by non-integrative reprogramming technology using OCT3/4, SOX2, CMYC and KLF4 reprogramming factors. The pluripotency was assessed by immunocytochemist...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2018.10.016

    authors: Machuca C,Vilches A,Clemente E,Pascual-Pascual SI,Bolinches-Amorós A,Artero Castro A,Espinos C,Leon M,Jendelova P,Erceg S

    更新日期:2018-12-01 00:00:00

  • Generation of KCL035 research grade human embryonic stem cell line carrying a mutation in HBB gene.

    abstract::The KCL035 human embryonic stem cell line was derived from an embryo donated for research that carried a mutation in the HBB gene, which is linked to the β-thalassemia syndrome. The ICM was isolated using laser microsurgery and plated on γ-irradiated human foreskin fibroblasts. Both the derivation and cell line propag...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2016.01.007

    authors: Hewitson H,Wood V,Kadeva N,Cornwell G,Codognotto S,Stephenson E,Ilic D

    更新日期:2016-03-01 00:00:00

  • Generation of four induced pluripotent stem cell lines, GZWWTi001-A, GZWTZi001-A, GZWXYi001-A, and GZWXDi001-A, derived from peripheral blood mononuclear cells from a family with asparagine synthetase deficiency.

    abstract::Asparagine synthetase (ASNS) deficiency (ASNSD; MIM #615574) is a rare neurodevelopmental disorder caused by mutations in the ASNS gene. The ASNS gene maps to cytogenetic band 7q21.3 and is 35 kb long. ASNSD is characterised by congenital microcephaly, severely delayed psychomotor development, seizures, and hyperekple...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2019.101583

    authors: Yingjun X,Dian L,Ding W,Shaoying L,Yinghong Y,Nengqing L,Xiaofang S

    更新日期:2019-12-01 00:00:00

  • Generation of integration-free induced pluripotent stem cells from a patient with spina bifida.

    abstract::A skin biopsy was obtained from a 14-year-old female patient with a history of Myelomeningocele. Dermal fibroblasts were isolated and reprogrammed with Sendai virus (SeV) vectors encoding OCT3/4, SOX2, KLF4, and c-MYC. The generated induced Pluripotent Stem Cell (iPSC) clones NTDi4_09A were free of genomically integra...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2018.05.007

    authors: Wang H,Zhao S,Finnell RH,George T,Cooney AJ

    更新日期:2018-08-01 00:00:00

  • Generation of hiPSC line TCIERi001-A from normal human epidermal keratinocytes.

    abstract::Human induced pluripotent stem cell (hiPSC) line TCIERi001-A was generated from normal human epidermal keratinocytes (NHEK) primary cell line with the nonintegrating system using Sendai reprogramming kit. Sendai particles were used to deliver the defined transcription factors that included three vector preparations, s...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2019.101590

    authors: Shrestha R,Wen YT,Tsai RK

    更新日期:2019-12-01 00:00:00

  • Generation of a genetically modified human embryonic stem cells expressing fluorescence tagged ATOX1.

    abstract::ATOX1 is a copper chaperone involved in intracellular copper homeostasis, cell proliferation, and tumor progression. To investigate the physiologically relevant molecular mechanism of ATOX1 by using imaging-based approaches, we genetically modified ATOX1 in H1 hESCs to express mCherry-ATOX1 fusion protein under endoge...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2019.101631

    authors: Wen MH,Xie X,Tu J,Lee DF,Chen TY

    更新日期:2019-12-01 00:00:00

  • A co-culture model of the hippocampal neurogenic niche reveals differential effects of astrocytes, endothelial cells and pericytes on proliferation and differentiation of adult murine precursor cells.

    abstract::The niche concept of stem cell biology proposes a functional unit between the precursor cells and their local microenvironment, to which several cell types might contribute by cell-cell contacts, extracellular matrix, and humoral factors. We here established three co-culture models (with cell types separated by membra...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2015.09.010

    authors: Ehret F,Vogler S,Kempermann G

    更新日期:2015-11-01 00:00:00

  • Lactate regulates myogenesis in C2C12 myoblasts in vitro.

    abstract::Satellite cells (SCs) are the resident stem cells of skeletal muscle tissue which play a major role in muscle adaptation, e.g. as a response to physical training. The aim of this study was to examine the effects of an intermittent lactate (La) treatment on the proliferation and differentiation of C2C12 myoblasts, simu...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2014.03.004

    authors: Willkomm L,Schubert S,Jung R,Elsen M,Borde J,Gehlert S,Suhr F,Bloch W

    更新日期:2014-05-01 00:00:00

  • Pluripotent stem cell-derived interneuron progenitors mature and restore memory deficits but do not suppress seizures in the epileptic mouse brain.

    abstract::GABAergic interneuron dysfunction has been implicated in temporal lobe epilepsy (TLE), autism, and schizophrenia. Inhibitory interneuron progenitors transplanted into the hippocampus of rodents with TLE provide varying degrees of seizure suppression. We investigated whether human embryonic stem cell (hESC)-derived int...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2018.10.007

    authors: Anderson NC,Van Zandt MA,Shrestha S,Lawrence DB,Gupta J,Chen CY,Harrsch FA,Boyi T,Dundes CE,Aaron G,Naegele JR,Grabel L

    更新日期:2018-12-01 00:00:00

  • Generation of three induced pluripotent stem cell lines (MHHi012-A, MHHi013-A, MHHi014-A) from a family with Loeys-Dietz syndrome carrying a heterozygous p.M253I (c.759G>A) mutation in the TGFBR1 gene.

    abstract::Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder characterized by a genetic predisposition for thoracic aortic aneurysm and dissection. Despite heterozygous loss-of-function mutations in genes for ligand, receptor, or downstream mediators of the transforming growth factor β (TGFβ) pathway, LDS is associ...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2020.101707

    authors: Pongpamorn P,Dahlmann J,Haase A,Ebeling CT,Merkert S,Göhring G,Lachmann N,Martens A,Haverich A,Martin U,Olmer R

    更新日期:2020-03-01 00:00:00

  • Neuro-peptide treatment with Cerebrolysin improves the survival of neural stem cell grafts in an APP transgenic model of Alzheimer disease.

    abstract::Neural stem cells (NSCs) have been considered as potential therapy in Alzheimer's disease (AD) but their use is hampered by the poor survival of grafted cells. Supply of neurotrophic factors to the grafted cells has been proposed as a way to augment survival of the stem cells. In this context, we investigated the util...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2015.04.008

    authors: Rockenstein E,Desplats P,Ubhi K,Mante M,Florio J,Adame A,Winter S,Brandstaetter H,Meier D,Masliah E

    更新日期:2015-07-01 00:00:00

  • Comparative transcriptome analysis in induced neural stem cells reveals defined neural cell identities in vitro and after transplantation into the adult rodent brain.

    abstract::Reprogramming technology enables the production of neural progenitor cells (NPCs) from somatic cells by direct transdifferentiation. However, little is known on how neural programs in these induced neural stem cells (iNSCs) differ from those of alternative stem cell populations in vitro and in vivo. Here, we performed...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2016.04.015

    authors: Hallmann AL,Araúzo-Bravo MJ,Zerfass C,Senner V,Ehrlich M,Psathaki OE,Han DW,Tapia N,Zaehres H,Schöler HR,Kuhlmann T,Hargus G

    更新日期:2016-05-01 00:00:00

  • Insulin-like growth factor 1 can promote the osteogenic differentiation and osteogenesis of stem cells from apical papilla.

    abstract::Insulin-like growth factor 1 (IGF-1) plays an important role in the regulation of tooth root development, and stem cells from apical papilla (SCAPs) are responsible for the formation of root pulp and dentin. To date, it remains unclear whether IGF-1 can regulate the function of SCAPs. In this study, SCAPs were isolate...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2011.12.005

    authors: Wang S,Mu J,Fan Z,Yu Y,Yan M,Lei G,Tang C,Wang Z,Zheng Y,Yu J,Zhang G

    更新日期:2012-05-01 00:00:00

  • Derivation and characterization of the human embryonic stem cell line CR-4: Differentiation to human retinal pigment epithelial cells.

    abstract::The CR-4 human embryonic stem cell line was derived from the inner cell mass of a developing blastocyst. This cell line has been adapted to grow in feeder-free conditions and is especially well-suited for differentiation to retinal pigment epithelium. The line demonstrates a normal human 46,XX female karyotype. Plurip...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2016.12.005

    authors: Mazzilli JL,Domozhirov AY,Mueller-Ortiz SL,Garcia CA,Wetsel RA,Zsigmond EM

    更新日期:2017-01-01 00:00:00

  • Development of FGF2-dependent pluripotent stem cells showing naive state characteristics from murine preimplantation inner cell mass.

    abstract::Two distinct types of embryonic pluripotent stem cells can be established from either the inner cell mass (ICM) of preimplantation blastocyst (leukemia inhibitory factor (LIF)-dependent embryonic stem cell, ESC, called naive state) or the epiblast of postimplantation fetuses (fibroblast growth factor 2 (FGF2)-dependen...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2014.04.012

    authors: Ozawa M,Kawakami E,Sakamoto R,Shibasaki T,Goto A,Yoshida N

    更新日期:2014-07-01 00:00:00

  • Generation of non-integrated induced pluripotent stem cells from a 23-year-old male with multiple endocrine neoplasia type 1 syndrome.

    abstract::Urine resource cells were collected from a 23-year-old male with multiple endocrine neoplasia type 1 syndrome (MEN1) for generating iPS cells with episomal plasmids. Two stable iPSC lines with free of episomal plasmid were established. The patient has a heterozygous G>T mutation on the exon 9 of Men1 gene that was con...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2016.12.002

    authors: Guo D,Wu F,Liu H,Gao G,Kou S,Yang F,Abbas N,Zhou T,Cai X,Zhang H,Qin D,Li J,Xu K,Li YX

    更新日期:2017-01-01 00:00:00

  • An induced pluripotent stem cell line (SDQLCHi006-A) derived from a patient with maple syrup urine disease type Ib carrying compound heterozygous mutations of p.R168C and p.T322I in BCKDHB gene.

    abstract::Maple syrup urine disease type Ib (MSUD Ib) is an autosomal recessive genetic metabolic disease caused by homozygous or compound heterozygous mutation in BCKDHB on chromosome 6q14. We generated an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells (PBMCs) of a 5-day-old boy with MSUD Ib ...

    journal_title:Stem cell research

    pub_type: 杂志文章

    doi:10.1016/j.scr.2019.101579

    authors: Li Y,Zhang H,Yan B,Ma Y,Yang X,Guan J,Lv Y,Gao M,Ma J,Gai Z,Liu Y

    更新日期:2019-10-01 00:00:00