BMB reports 리뷰소개 : 배아 파생 줄기 세포-떠오르는 조직체

Bert Binas 한국생화학분자생물학회 (구 한국생화학회) 2009 생화학분자생물학회 소식 Vol.29 No.1

News and perspectives on yolk sac stem cells

Bert Binas 한국수정란이식학회 2016 한국수정란이식학회 학술대회 Vol.2016 No.10

The mammalian yolk sac endoderm is an essential but understudied tissue that patterns and nourishes the embryo. This talk will present the isolation and characterization of several categories of rodent yolk sac endoderm stem cells. Specifically, we have isolated yolk sac endoderm stem cell lines from preimplantation embryos and from post-gastrulation yolk sacs. In both cases, we obtained two versions of stem cells that appear to differ in their degree of lineage maturation. I will discuss the relationship of these various isolates within the same species (rat or mouse), between species (rat vs. mouse), and with previously published isolates. I will then discuss potential applications in developmental biotechnology and toxicology as well as the human relevance of this research.

News and perspectives on yolk sac stem cells

Bert Binas 한국동물생명공학회(구 한국동물번식학회) 2016 발생공학 국제심포지엄 및 학술대회 Vol.2016 No.10

Developmental Potential of Rat Extraembryonic Stem Cells

Galat, Vasiliy,Binas, Bert,Iannaccone, Stephen,Postovit, Lynne-Marie,Debeb, Bisrat G.,Iannaccone, Philip Mary Ann Liebert 2009 STEM CELLS AND DEVELOPMENT Vol.18 No.9

<P>We have previously found that certain stem cells that are derived from rat blastocysts and named extraembryonic endoderm precursor (XEN-P) cells show a unique molecular signature sharing some of the characteristics of embryonic stem cells (ES), trophoblast stem cells (TS), and extraembryonic endoderm stem cells (XEN). These XEN-P cells are positive for AP, SSEA1, Oct4, and Rex1 markers similar to ES cells and also express signature markers of TS-eomesodermin (Eomes) and XEN-Gata6. Here we show that these cells integrate into the visceral and parietal extraembryonic endoderm lineages as well as into the inner cell mass (ICM), the primitive endoderm, and the polar and mural trophectoderm (TE) of cultured embryos. In addition, we find that the XEN-P cells colonize yolk sac and contribute to trophoblast lineages of postimplantation embryos following transfer to surrogate mothers. We also find that the XEN-P cell culture propagates by shedding cell clusters into the media in addition to typical expansion of colonies. Interestingly, the cell cultures exist as mixed populations of two interconvertible phenotypes of flat and round cells with preferential expression of stem cell markers Oct4 and SSEA1 in round cells. We believe these cells represent a metastable stage during ICM cellular segregation. These results are important for developing hypotheses of cell fate plasticity in the ICM and provide a model for the study of development and differentiation along the extraembryonic lineages.</P>

Inflammatory mediators ATP and S100A12 activate the NLRP3 inflammasome to induce MUC5AC production in airway epithelial cells

Kim, Karam,Kim, Hye Jeong,Binas, Bert,Kang, Jin Hyun,Chung, Il Yup Elsevier 2018 Biochemical and biophysical research communication Vol.503 No.2

<P><B>Abstract</B></P> <P>Danger-associated molecular patterns (DAMPs) play a proinflammatory role in the pathogenesis of airway obstructive diseases such as severe asthma and chronic obstructive pulmonary disease. The NLRP3 inflammasome is a cytosolic multiprotein platform that activates the caspase-1 pathway in response to inflammatory stimuli such as DAMPs. ATP and S100 proteins are newly identified DAMPs that accumulate in inflamed airways. We previously demonstrated that S100A8, S100A9, and S100A12 induce production and secretion of MUC5AC, a major mucin in the conducting airway mucosa. The purpose of this study was to determine the involvement of NLRP3 inflammasome in, and the contribution of ATP to, S100 protein-induced MUC5AC production by NCI-H292 mucoepidermoid carcinoma cells. Stimulation with either S100A12 or ATP led to MUC5AC production at comparable levels. Simultaneous treatment with both stimuli resulted in additive increases in NLRP3, active caspase-1, IL-1β, NLRP3/caspase-1 colocalization, and MUC5AC. NLRP3 siRNA or inhibitors of NF-κB, NLRP3 inflammasome oligomerization, or caspase-1 nearly completely inhibited ATP- and S100A12-mediated MUC5AC production. Furthermore, S100A12-as well as ATP-mediated MUC5AC production was almost equally blunted by both nonspecific and specific antagonists of the purinergic receptor P2X7, a principal receptor mediating NLRP3 inflammasome activation by ATP. Thus, these two danger signals contribute to MUC5AC production in airway epithelial cells through overlapping signaling pathways for NLRP3 inflammasome activation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> S100A12 activates NLPR3 inflammasomes to induce MUC5AC production in epithelial cells. </LI> <LI> ATP induces MUC5AC production in a mechanistically similar mode to S100A12. </LI> <LI> S100A12-mediated MUC5AC production involves engagement of ATP. </LI> </UL> </P>

Analysis of SSEA1+ vs. SSEA1- fractions of bulk-cultured XENP cell lines

Minjin Jeong,Kyeng-Won Choi,김승준,김정호,Bert Binas 한국바이오칩학회 2012 BioChip Journal Vol.6 No.1

Previously isolated rat extraembryonic endoderm precursor (XENP) cell lines had been characterized after clonal density plating. The arising colonies had consisted of peripheral XENP cells expressing the surface antigen SSEA1 and the transcription factor Oct4, and inner XENP-derived extraembryonic endoderm cells that were nearly negative for SSEA1 and Oct4. We now sorted bulk-cultured XENP cell lines from two rat strains by FACS into SSEA1+ and SSEA1- populations and compared their expression profiles by microarray and RT-PCR. In the bulk cultures, the SSEA1+ fraction was only slightly enriched for Oct4, and also slightly enriched for the visceral endoderm markers, Dab2 and Ihh. Both fractions expressed vascular-associated mesodermal markers (VE-cadherin, Flk1). Thus, in regular-density XENP cell cultures, SSEA1 is not suitable as a stem cell marker, and the XENP cells appear to undergo partial somatic differentiation.

Isolation of primitive mouse extraembryonic endoderm (pXEN) stem cell lines

Zhong, Yixiang,Choi, Taewoong,Kim, Minjae,Jung, Kyoung Hwa,Chai, Young Gyu,Binas, Bert Elsevier 2018 Stem cell research Vol.30 No.-

<P><B>Abstract</B></P> <P>Mouse blastocysts contain the committed precursors of the extraembryonic endoderm (ExEn), which express the key transcription factor Oct4, depend on LIF/LIF-like factor-driven Jak/Stat signaling, and initially exhibit lineage plasticity. Previously described rat blastocyst-derived ExEn precursor-like cell lines (XENP cells/HypoSCs) also show these features, but equivalent mouse blastocyst-derived cell lines are lacking. We now present mouse blastocyst-derived cell lines, named primitive XEN (pXEN) cells, which share these and additional characteristics with the XENP cells/HypoSCs, but not with previously known mouse blastocyst-derived XEN cell lines. Otherwise, pXEN cells are highly similar to XEN cells by morphology, lineage-intrinsic differentiation potential, and multi-gene expression profile, although the pXEN cell profile correlates better with the blastocyst stage. Finally, we show that pXEN cells easily convert into XEN-like cells but not vice versa. The findings indicate that (i) pXEN cells are more representative than XEN cells of the blastocyst stage; (ii) mouse pXEN, rather than XEN, cells are homologs of rat XENP cells/HypoSCs, which we propose to call rat pXEN cells.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We present novel mouse extraembryonic endoderm stem cell lines (pXEN cells). </LI> <LI> pXEN cells show preimplantation-stage features not shown by XEN cells. </LI> <LI> pXEN cells are easily converted into XEN-like cells but not vice versa. </LI> <LI> pXEN cells are homologous to previously described rat XENP cells/HypoSCs. </LI> </UL> </P> <P>Graphical abstract</P> <P>[DISPLAY OMISSION]</P>

Olig2 is expressed late in human eosinophil development and controls Siglec-8 expression

Hwang, Sae Mi,Uhm, Tae Gi,Lee, Seol Kyung,Kong, Su-Kang,Jung, Kyung Hwa,Binas, Bert,Chai, Young Gyu,Park, Sung Woo,Chung, Il Yup Wiley (John WileySons) 2016 Journal of leukocyte biology Vol.100 No.4

<P>Oligodendrocyte transcription factor 2, a basic helix-loop-helix transcription factor that binds to E-box motifs, is known to have a key role in determining lineage specification of oligodendrocytes and motor neurons. In the present study, we report that oligodendrocyte transcription factor 2 is expressed in human eosinophils and involved in transcriptional activation of the gene encoding sialic acid binding immunoglobulin-like lectin 8 (Siglec-8), a late eosinophil-differentiation marker known to exert eosinophil apoptosis. When cord blood CD34(+) hematopoietic stem cells differentiated toward eosinophils during a 24-d culture period, oligodendrocyte transcription factor 2 protein was expressed in cord blood eosinophils on d 24, a time when cord blood eosinophils are considered fully differentiated, whereas it was not detectable on d 18 or at earlier time points. Oligodendrocyte transcription factor 2 protein was also abundantly expressed in human peripheral-blood eosinophils but not in neutrophils, monocytes, lymphocytes, or cord blood mast cells. RNA sequencing analysis showed that numerous genes, especially those encoding eosinophil surface molecules, were highly up-regulated along with OLIG2. Among the genes examined, SIGLEC-8 messenger RNA and protein were markedly downregulated in parallel with OLIG2 by an oligodendrocyte transcription factor 2 small interfering RNA or a short hairpin RNA, as evidenced by real-time polymerase chain reaction, fluorescence-activated cell sorting, and Western blot analyses. In reporter gene and chromatin immunoprecipitation experiments, an E-box in the first intron was found to stimulate SIGLEC-8 gene transcription and to bind oligodendrocyte transcription factor 2. Hence, at least one important aspect of eosinophil differentiation is regulated by oligodendrocyte transcription factor 2, a transcription factor that has not previously been reported, to our knowledge, in normal granulocytes.</P>

Forkhead box O1 (FOXO1) controls the migratory response of Toll-like receptor (TLR3)-stimulated human mesenchymal stromal cells

Hwa Kim, Sun,Das, Amitabh,In Choi, Hae,Hoon Kim, Ki,Choul Chai, Jin,Ran Choi, Mi,Binas, Bert,Sun Park, Kyoung,Seek Lee, Young,Jung, Kyoung Hwa,Gyu Chai, Young American Society for Biochemistry and Molecular Bi 2019 The Journal of biological chemistry Vol.294 No.21

<P>Mesenchymal stromal cells (MSCs) can potently regulate the functions of immune cells and are being investigated for the management of inflammatory diseases. Toll-like receptor 3 (TLR3)-stimulated human MSCs (hMSCs) exhibit increased migration and chemotaxis within and toward damaged tissues. However, the regulatory mechanisms underlying these migratory activities are unclear. Therefore, we analyzed the migration capability and gene expression profiles of TLR3-stimulated hMSCs using RNA-Seq, wound healing, and transwell cell migration assay. Along with increased cell migration, the TLR3 stimulation also increased the expression of cytokines, chemokines, and cell migration-related genes. The promoter regions of the latter showed an enrichment of putative motifs for binding the transcription factors forkhead box O1 (FOXO1), FOXO3, NF-κB (NF-κB1), and RELA proto-oncogene and NF-κB subunit. Of note, FOXO1 inhibition by the FOXO1-selective inhibitor AS1842856 significantly reduced both migration and the expression of migration-related genes. In summary, our results indicate that TLR3 stimulation induces hMSC migration through the expression of FOXO1-activated genes.</P>