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子宫多发性恶性中胚叶混合瘤1例报道并文献复习 被引量:8
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作者 陆怡 吴红阳 +2 位作者 彭万仁 胡向阳 孙国平 《罕少疾病杂志》 2011年第1期40-43,共4页
目的探讨子宫恶性中胚叶混合瘤(malignant mixed mesodermal tumor,MMMT)的临床表现、组织学类型及治疗。方法结合1例子宫恶性中胚叶混合瘤伴肝腹腔转移患者的临床资料并进行文献复习。结论子宫恶性中胚叶混合瘤MMMT临床表现缺乏特异性... 目的探讨子宫恶性中胚叶混合瘤(malignant mixed mesodermal tumor,MMMT)的临床表现、组织学类型及治疗。方法结合1例子宫恶性中胚叶混合瘤伴肝腹腔转移患者的临床资料并进行文献复习。结论子宫恶性中胚叶混合瘤MMMT临床表现缺乏特异性,主要表现为不规则阴道流血,诊断性刮宫对其确诊有较大的帮助。组织学上分为同源性和异源性,治疗以综合治疗为主,手术是目前治疗子宫恶性中胚叶混合瘤MMMT的主要治疗方法,术后根据肿瘤部位采用放疗和化疗。该疾病恶性程度高,预后较差。 展开更多
关键词 子宫恶性中胚叶混合瘤 MALIGNANT MIXED mesodermal TUMOR 诊断 治疗
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Diagnostics and Prediction of Glaucoma in Patients with Familial Congenital Iris Hypoplasia 被引量:2
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作者 Tatiana Iureva Andrey Shchuko Yulia Pyatova 《Open Journal of Ophthalmology》 2015年第3期115-123,共9页
Purpose: To identify the clinical features of the syndrome Frank-Kamenetsky and determine the criteria of early formation of glaucoma. Materials and Methods: We observed 52 patients. Follow up period was from 5 to 22 ... Purpose: To identify the clinical features of the syndrome Frank-Kamenetsky and determine the criteria of early formation of glaucoma. Materials and Methods: We observed 52 patients. Follow up period was from 5 to 22 years. The first group (juvenile) consisted of males who had the first signs of glaucoma diagnosed before the age of 12 (n = 22). The average age of the group was 10.1 ± 2.4 years. The control group included healthy males (n = 30) in the same age range (average age 7.2 ± 1.6 years). The second group (adults) consisted of patients who had the first signs of glaucoma diagnosed after the age of 18 and elder. The average age of the group was 32.44 ± 6.28 years. The control group had males (n = 30) in the same age range (average age 26.59 ± 4.12 years). The inclusion criterion was: the presence of congenital bilateral mesodermal iris leaf hypoplasia, tra-becular dysgenesis signs, the presence of blood relatives on the maternal line (grandfather, uncle) male with similar changes iridociliary zone and glaucoma. Criteria of glaucoma formation were: increased IOP more than 21 mmHg with accompanying it expansion of the cup/disc ratio, reducing the thickness of the nerve fiber layer (RNFL) according to OCT. Results: It was found that Frank-Kamenetsky Syndrome had an X-linked with sex, recessive inheritance and was characterized by bilateral congenital irisdysgenesis and goniodysgenesis with the accession glaucoma. Predictors of glaucoma formation in early childhood are a combination of: 1) congenital subtotal atrophy of iris mesodermal layer (from 0 to 30 mkm) with signs of progressive dystrophy;2) nonprogressive congenital megalocornea (cornea diameter 12 - 14 mm);3) iridotrabecular dysgenesis of II-III degree;4) hyperopic refraction in axial myopia. 展开更多
关键词 GLAUCOMA Megalocornea CONGENITAL mesodermal IRIS ATROPHY Goniodysgenesis
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Mass acquisition of human periodontal ligament stem cells 被引量:4
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作者 Hidefumi Maeda 《World Journal of Stem Cells》 SCIE CAS 2020年第9期1023-1031,共9页
The periodontal ligament(PDL)is an essential fibrous tissue for tooth retention in the alveolar bone socket.PDL tissue further functions to cushion occlusal force,maintain alveolar bone height,allow orthodontic tooth ... The periodontal ligament(PDL)is an essential fibrous tissue for tooth retention in the alveolar bone socket.PDL tissue further functions to cushion occlusal force,maintain alveolar bone height,allow orthodontic tooth movement,and connect tooth roots with bone.Severe periodontitis,deep caries,and trauma cause irreversible damage to this tissue,eventually leading to tooth loss through the destruction of tooth retention.Many patients suffer from these diseases worldwide,and its prevalence increases with age.To address this issue,regenerative medicine for damaged PDL tissue as well as the surrounding tissues has been extensively investigated regarding the potential and effectiveness of stem cells,scaffolds,and cytokines as well as their combined applications.In particular,PDL stem cells(PDLSCs)have been well studied.In this review,I discuss comprehensive studies on PDLSCs performed in vivo and contemporary reports focusing on the acquisition of large numbers of PDLSCs for therapeutic applications because of the very small number of PDLSCs available in vivo. 展开更多
关键词 Induced pluripotent stem cells Mesoderm specific transcript Periodontal ligament stem cells Periodontal tissue Regenerative medicine Semaphorin 3A
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Tonsil-derived stem cells as a new source of adult stem cells 被引量:3
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作者 Kyung-Ah Cho Hyun Jung Lee +8 位作者 Hansaem Jeong Miri Kim Soo Yeon Jung Hae Sang Park Kyung-Ha Ryu Seung Jin Lee Byeongmoon Jeong Hyukjin Lee Han Su Kim 《World Journal of Stem Cells》 SCIE 2019年第8期506-518,共13页
Located near the oropharynx, the tonsils are the primary mucosal immune organ. Tonsil tissue is a promising alternative source for the high-yield isolation of adult stem cells, and recent studies have reported the ide... Located near the oropharynx, the tonsils are the primary mucosal immune organ. Tonsil tissue is a promising alternative source for the high-yield isolation of adult stem cells, and recent studies have reported the identification and isolation of tonsil-derived stem cells (T-SCs) from waste surgical tissue following tonsillectomies in relatively young donors (i.e., under 10 years old). As such, TSCs offer several advantages, including superior proliferation and a shorter doubling time compared to bone marrow-derived mesenchymal stem cells (MSCs). T-SCs also exhibit multi-lineage differentiation, including mesodermal, endodermal (e.g., hepatocytes and parathyroid-like cells), and even ectodermal cells (e.g., Schwann cells). To this end, numbers of researchers have evaluated the practical use of T-SCs as an alternative source of autologous or allogenic MSCs. In this review, we summarize the details of T-SC isolation and identification and provide an overview of their application in cell therapy and regenerative medicine. 展开更多
关键词 STEM CELL Tonsil-derived STEM CELL Differentiation ENDODERM Mesoderm ECTODERM CELL therapy
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Identification and characterization of human hematopoietic mesoderm
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作者 Yuqi Wen Jingjing Zhao +12 位作者 Runqing Zhang Fan Liu Xiaoyuan Chen Dan Wu Mengge Wang Cuicui Liu Pei Su Panpan Meng Yiyue Zhang Xin Gao Lu Wang Hongtao Wang Jiaxi Zhou 《Science China(Life Sciences)》 SCIE CAS CSCD 2024年第2期320-331,共12页
The embryonic mesoderm comprises heterogeneous cell subpopulations with distinct lineage biases.It is unclear whether a bias for the human hematopoietic lineage emerges at this early developmental stage.In this study,... The embryonic mesoderm comprises heterogeneous cell subpopulations with distinct lineage biases.It is unclear whether a bias for the human hematopoietic lineage emerges at this early developmental stage.In this study,we integrated single-cell transcriptomic analyses of human mesoderm cells from embryonic stem cells and embryos,enabling us to identify and define the molecular features of human hematopoietic mesoderm(HM)cells biased towards hematopoietic lineages.We discovered that BMP4 plays an essential role in HM specification and can serve as a marker for HM cells.Mechanistically,BMP4 acts as a downstream target of HDAC1,which modulates the expression of BMP4 by deacetylating its enhancer.Inhibition of HDAC significantly enhances HM specification and promotes subsequent hematopoietic cell differentiation.In conclusion,our study identifies human HM cells and describes new mechanisms for human hematopoietic development. 展开更多
关键词 hematopoietic mesoderm human pluripotent stem cells human embryos BMP4 HDAC1
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Maternal Eomesodermin regulates zygotic nodal gene expression for mesendoderm induction in zebrafish embryos 被引量:5
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作者 Pengfei Xu Gaoyang Zhu Yixia Wang Jiawei Sun Xingfeng Liu Ye-Guang Chen Anming Meng 《Journal of Molecular Cell Biology》 SCIE CAS CSCD 2014年第4期272-285,共14页
Development of animal embryos before zygotic genome activation at the mid blastula transition (MBT) is essentially supported by eggderived maternal products. Nodal proteins are crucial signals for mesoderm and endod... Development of animal embryos before zygotic genome activation at the mid blastula transition (MBT) is essentially supported by eggderived maternal products. Nodal proteins are crucial signals for mesoderm and endoderm induction after the MBT. It remains unclear which maternal factors activate zygotic expression of nodal genes in the ventrotateral blastodermal margin of the zebrafish blastulas. In this study, we show that loss of maternal Eomesodermin a (Eomesa), a T-box transcription factor, impairs zygotic expression of the nodal genes ndr1 and ndr2 as well as mesodermal and endodermal markers, indicating an involvement in mesendoderm induction. Maternal Eomesa is also required for timely zygotic expression of the transcription factor gene mxtx2, a regulator of nodal gene expression. Eomesa directly binds to the Eomes-binding sites in the promoter or enhancer of ndr1, ndr2, and rnxtx2 to activate their transcrip- tion. Furthermore, human and mouse Nodal genes are also regulated by Eomes. Transfection of zebrafish eomesa into murine embryonic stem cells promotes mesendodermal differentiation with constant higher levels of endogenous Nodal expression, suggesting a conserved function of Eomes. Taken together, our findings reveal a conserved rote of maternal T-box transcription factors in regulating nodal gene expression and mesendoderm induction in vertebrate embryos. 展开更多
关键词 EOMESODERMIN NODAL transcription MESODERM ENDODERM EMBRYO zebrafish
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Inducible overexpression of RUNX1b/c in human embryonic stem cells blocks early hematopoiesis from mesoderm 被引量:4
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作者 Bo Chen Jiawen Teng +11 位作者 Hongwei Liu Xu Pan Ya Zhou Shu Huang Mowen Lai Guohui Bian Bin Mao Wencui Sun Qiongxiu Zhou Shengyong Yang Tatsutoshi Nakahata Feng Ma 《Journal of Molecular Cell Biology》 SCIE CAS CSCD 2017年第4期262-273,共12页
RUNXI is absolutely required for definitive hematopoiesis, but the function of RUNXlb/c, two isoforms of human RUNX1, is unclear. We established inducible RUNXlb/c-overexpressing human embryonic stem cell (hESC) lin... RUNXI is absolutely required for definitive hematopoiesis, but the function of RUNXlb/c, two isoforms of human RUNX1, is unclear. We established inducible RUNXlb/c-overexpressing human embryonic stem cell (hESC) lines, in which RUNXlb/c overexpression prevented the emergence of CD34+ cells from early stage, thereby drastically reducing the production of hematopoi- etic stem/prognnitor cells. Simultaneously, the expression of hematopoiesis-related factors was downregulated. However, such blockage effect disappeared from day 6 in hESC/AGM-S3 ceU co-cultures, proving that the blockage occurred before the generation of hemogenic endothelial cells. This blockage was partially rescued by RepSox, an inhibitor of the transforming growth factor (TGF)-β signaling pathway, indicating a close relationship between RUNX1b/c and TGF-β pathway. Our results suggest a unique inhibitory function of RUNX1b/c in the development of early hematopoiesis and may aid further understanding of its biological function in normal and diseased models. 展开更多
关键词 RUNX1/AML1 HEMATOPOIESIS hemogenic endothelium MESODERM TGF-β signaling pathway HESC inducible expressionsystem
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VprBP mitigates TGF-β and Activin signaling by promoting Smurf1-mediated type Ⅰ receptor degradation 被引量:3
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作者 Yihao Li Chao Cui +7 位作者 Feng Xie Szymon Kietbasa Hailiang Mei Maarten van Dinther Hans van Dam Andreas Bauer Long Zhang Peterten Dijke 《Journal of Molecular Cell Biology》 SCIE CAS CSCD 2020年第2期138-151,共14页
The transforming growth factor-β(TGF-β)family controls embryogenesis,stem cell differentiation,and tissue homeostasis.However,how post-translation modifications contribute to fine-tuning of TGF-βfamily signaling re... The transforming growth factor-β(TGF-β)family controls embryogenesis,stem cell differentiation,and tissue homeostasis.However,how post-translation modifications contribute to fine-tuning of TGF-βfamily signaling responses is not well understood.Inhibitory(I)-Smads can antagonize TGF-β/Smad signaling by recruiting Smurf E3 ubiquitin ligases to target the active TGF-βreceptor for proteasomal degradation.A proteomic interaction screen identified Vpr binding protein(VprBP)as novel binding partner of Smad7.Mis-expression studies revealed that VprBP negatively controls Smad2 phosphorylation,Smad2–Smad4 interaction,as well as TGF-βtarget gene expression.VprBP was found to promote Smad7–Smurf1–TβRI complex formation and induce proteasomal degradation of TGF-βtype I receptor(TβRI).Moreover,VprBP appears to stabilize Smurf1 by suppressing Smurf1 poly-ubiquitination.In multiple adult and mouse embryonic stem cells,depletion of VprBP promotes TGF-βor Activin-induced responses.In the mouse embryo VprBP expression negatively correlates with mesoderm marker expression,and VprBP attenuated mesoderm induction during zebrafish embryogenesis.Our findings thereby uncover a novel regulatory mechanism by which Smurf1 controls the TGF-βand Activin cascade and identify VprBP as a critical determinant of embryonic mesoderm induction. 展开更多
关键词 Smurfl TGF-βtype I receptor UBIQUITINATION ACTIVIN mesoderm induction
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IP3R-mediated Ca2+ signals govern hematopoietic and cardiac divergence of Flk1+ cells via the calcineurin-N FATc3-Etv2 pathway 被引量:3
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作者 Yi-Jie Wang Jijun Huang +7 位作者 Wenqiang Liu Xiaochen Kou Huayuan Tang Hong Wang Xiujian Yu Shaorong Gao Kunfu Ouyang Huang-Tian Yang 《Journal of Molecular Cell Biology》 SCIE CAS CSCD 2017年第4期274-288,共15页
Ca2+ signals participate in various cellular processes with spatial and temporal dynamics, among which, inositol 1,4,5-trisphosphate receptors (IP3Rs)-mediated Ca2+ signals are essential for early development. How... Ca2+ signals participate in various cellular processes with spatial and temporal dynamics, among which, inositol 1,4,5-trisphosphate receptors (IP3Rs)-mediated Ca2+ signals are essential for early development. However, the underlying mechanisms of IP3R- regulated cell fate decision remain largely unknown. Here we report that IP3Rs are required for the hematopoietic and cardiac fate divergence of mouse embryonic stem cells (mESCs). Deletion of IP3Rs (IP3R-tKO) reduced FIkl+/PDGFRα- hematopoietic mesoderm, c-Kit+/CD41+ hematopoietic progenitor ceil population, and the colony-forming unit activity, but increased cardiac progenitor markers as well as cardiomyocytes. Concomitantly, the expression of a key regulator of hematopoiesis, Ely2, was reduced in IP3R-tKO cells, which could be rescued by the activation of Ca2+ signals and calcineurin or overexpression of constitutively active form of NFATc3. Furthermore, IP3R-tKO impaired specific targeting of Ely2 by NFATc3 via its evolutionarily conserved cis-element in differentiating ESCs. Importantly, the activation of Ca2+-calcineurin-NFAT pathway reversed the phenotype of IP3R-tKO cells. These findings reveal an unrecognized governing role of IP3Rs in hematopoietic and cardiac fate commitment via IP3Rs-Ca2+-calcineurin-NFATc3- Etv2 pathway. 展开更多
关键词 IP3Rs Ca2+ signals mesoderm specification hematopoietic and cardiac fate Etv2
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Molecular analyses of Xenopus laevis Mesp-related genes
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作者 Keisuke HITACHI Akiko KONDOW +3 位作者 Hiroki DANNO Yusuke NISHIMURA Koji OKABAYASHI Makoto ASASHIMA 《Integrative Zoology》 SCIE CSCD 2009年第4期387-394,共8页
During vertebrate somitogenesis,somites bud off from the anterior end of the presomitic mesoderm(PSM).Meso-dermal posterior(Mesp)-related genes play essential roles in somitogenesis,particularly in the definition of t... During vertebrate somitogenesis,somites bud off from the anterior end of the presomitic mesoderm(PSM).Meso-dermal posterior(Mesp)-related genes play essential roles in somitogenesis,particularly in the definition of the somite boundary position.Among vertebrates,two types of Mesp-related genes have been identified:Mesp1 and Mesp2 in the mouse;Meso-1 and Meso-2 in the chicken;Xl-mespa and Xl-mespb(also known as Thylacine1)in the African clawed frog(Xenopus laevis);and mesp-a and mesp-b in the zebrafish.However,the functional differences between two Mesp-related genes remain unknown.In the present study,we carried out comparative analyses of the Xl-mespa and Xl-mespb genes.The amino acid sequences of the Xl-mespa and Xl-mespb proteins showed a high level of similarity.The expression of Xl-mespa started broadly in the ventrolateral mesoderm and gradually shifted to a striped pattern of expression.In contrast,Xl-mespb showed a striped pattern of expression from the start.These expression profiles completely overlapped at the PSM during somitogenesis.To investigate the functional differ-ences between Xl-mespa and Xl-mespb in terms of target gene regulation,we carried out a luciferase assay using the murine Lunatic fringe(L-fng)promoter.Transcription of the L-fng promoter was activated more strongly by Xl-mespb than by Xl-mespa.This same pattern was observed for the murine Mesp-related proteins.These results suggest that the functional differences between the two types of Mesp-related genes are evolutionally conserved in vertebrates. 展开更多
关键词 HOMOLOGY presomitic mesoderm somite segmentation SOMITOGENESIS Xenopus laevis.
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RUNX1-205, a novel splice variant of the human RUNX1 gene, has blockage effect on mesoderm-hemogenesis transition and promotion effect during the late stage of hematopoiesis
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作者 Wencui Sun Jiahui Zeng +10 位作者 Jing Chang Yuan Xue Yonggang Zhang Xu Pan Ya Zhou Mowen Lai Guohui Bian Qiongxiu Zhou Jiaxing Liu Bo Chen Feng Ma 《Journal of Molecular Cell Biology》 SCIE CAS CSCD 2020年第5期386-396,共11页
Runt-related transcription factor 1(RUNX1)is required for definitive hematopoiesis;however,the functions of most human RUNX1 isoforms are unclear.In particular,the effects of RUNX1-205(a novel splice variant that lack... Runt-related transcription factor 1(RUNX1)is required for definitive hematopoiesis;however,the functions of most human RUNX1 isoforms are unclear.In particular,the effects of RUNX1-205(a novel splice variant that lacks exon 6 in comparison with RUNX1b)on human hematopoiesis are not clear.In this study,a human embryonic stem cell(hESC)line with inducible RUNX1-205 overexpression was established.Analyses of these cells revealed that induction of RUNX1-205 overexpression at early stage did not influence the induction of mesoderm but blocked the emergence of CD34+cells,and the production of hematopoietic stem/progenitor cells was significantly reduced.In addition,the expression of hematopoiesis-related factors was downregulated.However,these effects were abolished when RUNX1-205 overexpression was induced after Day 6 in co-cultures of hESCs and AGM-S3 cells,indicating that the inhibitory effect occurred prior to generation of hemogenic endothelial cells,while the promotive effect could be observed during the late stage of hematopoiesis.This is very similar to that of RUNX1b.Interestingly,the mRNA expression profile of RUNX1-205 during hematopoiesis was distinct from that of RUNX1b,and the protein stability of RUNX1-205 was much higher than that of RUNX1b.Thus,the function of RUNX1-205 in normal and diseased models should be further explored. 展开更多
关键词 mesoderm-hemogenesis TRANSITION HEMATOPOIESIS hematopoietic stem/progenitor CELLS (HSPCs) RUNX1 MESODERM embryonic STEM CELLS (ESCs)
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Zichong granules(资冲颗粒)promote differentiation of ovarian granulosa-like cells from human embryonic stem cells in vitro
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作者 YAO Zouying WANG Jing +4 位作者 LU Hua LI Limin ZHUO Tianxiu WAN Qian YIE Shangmian 《Journal of Traditional Chinese Medicine》 SCIE CSCD 2021年第2期203-211,共9页
OBJECTIVE:To investigate whether Zichong granules(资冲颗粒,ZCKL),a very effective herbal formula for treating infertility,have an impact on the differentiation of ovarian granulosa cells from human embryonic stem cell... OBJECTIVE:To investigate whether Zichong granules(资冲颗粒,ZCKL),a very effective herbal formula for treating infertility,have an impact on the differentiation of ovarian granulosa cells from human embryonic stem cells(hESCs)in vitro,and to explore the cellular mechanisms of its clinical effects.METHODS:Serum from ZCKL-medicated rats was prepared and used to treat mesoderm cells derived from hESCs for 6 d.Normal rat serum and a set of growth factors were used as negative and positive controls,respectively.RESULTS:ZCKL-medicated rat serum,but not normal rat serum,induced hESCs-derived mesoderm cells to differentiate into functional ovarian granulosa-like cells(OGLCs)in a similar manner to defined growth factors.The induced OGLCs resembled the morphology of native human granulosa cells,expressed granulosa cell-specific markers at both the mRNA and protein levels,produced high levels of estradiol and strongly responded to follicle-stimulating hormone stimulation.Furthermore,mRNA levels of follistatin,mothers against decapentaplegic homolog 8 and bone morphogenetic protein 6 were dynamically changed during the process.CONCLUSION:In the ZCKL treatment of infertility,one mechanism by which ZCKL may act is by influencing ovarian granulosa cell differentiation and development,possibly through the follistatin and BMP/SMAD signaling pathways. 展开更多
关键词 human embryonic stem cells INFERTILITY serum MESODERM OVARIAN granulosa cells Zichong granules
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CTCF acetylation at lysine 20 is required for the early cardiac mesoderm differentiation of embryonic stem cells
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作者 Shixin Gong Gongcheng Hu +5 位作者 Rong Guo Jie Zhang Yiqi Yang Binrui Ji Gang Li Hongjie Yao 《Cell Regeneration》 2022年第1期348-364,共17页
The CCCTC-binding factor(CTCF)protein and its modified forms regulate gene expression and genome organization.However,information on CTCF acetylation and its biological function is still lacking.Here,we show that CTCF... The CCCTC-binding factor(CTCF)protein and its modified forms regulate gene expression and genome organization.However,information on CTCF acetylation and its biological function is still lacking.Here,we show that CTCF can be acetylated at lysine 20(CTCF-K20)by CREB-binding protein(CBP)and deacetylated by histone deacetylase 6(HDAC6).CTCF-K20 is required for the CTCF interaction with CBP.A CTCF point mutation at lysine 20 had no effect on self-renewal but blocked the mesoderm differentiation of mouse embryonic stem cells(mESCs).The CTCF-K20 mutation reduced CTCF binding to the promoters and enhancers of genes associated with early cardiac mesoderm differentia-tion,resulting in diminished chromatin accessibility and decreased enhancer-promoter interactions,impairing gene expression.In summary,this study reveals the important roles of CTCF-K20 in regulating CTCF genomic functions and mESC differentiation into mesoderm. 展开更多
关键词 CTCF CTCF acetylation CBP HDAC6 Early cardiac mesoderm differentiation
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Overexpression of HOXA9 upregulates NF-κB signaling to promote human hematopoiesis and alter the hematopoietic differentiation potentials
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作者 Jiahui Zeng Danying Yi +13 位作者 Wencui Sun Yuanlin Liu Jing Chang Lijiao Zhu Yonggang Zhang Xu Pan Yong Dong Ya Zhou Mowen Lai Guohui Bian Qiongxiu Zhou Jiaxin Liu Bo Chen Feng Ma 《Cell Regeneration》 2021年第1期95-106,共12页
Background: The HOX genes are master regulators of embryogenesis that are also involved inhematopoiesis. HOXA9 belongs to a cluster of HOX genes that play extensively studied roles inhematopoiesis and leukemogenesis.M... Background: The HOX genes are master regulators of embryogenesis that are also involved inhematopoiesis. HOXA9 belongs to a cluster of HOX genes that play extensively studied roles inhematopoiesis and leukemogenesis.Methods: We established HOXA9-inducible human embryonic stem cells (HOXA9/hESCs) with normalpluripotency and potential for hematopoiesis, which could be used to analyze gene function with highaccuracy. HOXA9/hESCs co-cultured with aorta–gonad–mesonephros-derived stromal cells (AGM-S3) wereinduced to overexpress HOXA9 with doxycycline (DOX) at various times after hematopoiesis started andthen subjected to flow cytometry.Results: Induction of HOXA9 from Day 4 (D4) or later notably promoted hematopoiesis and also increasedthe production of CD34+ cells and derived populations. The potential for myelogenesis was significantlyelevated while the potential for erythrogenesis was significantly reduced. At D14, a significant promotion ofS phase was observed in green fluorescent protein positive (GFP+) cells overexpressing HOXA9. NF-κBsignaling was also up-regulated at D14 following induction of HOXA9 on D4. All of these effects could becounteracted by addition of an NF-κB inhibitor or siRNA against NFKB1 along with DOX.Conclusions: Overexpression of HOXA9 starting at D4 or later during hematopoiesis significantly promotedhematopoiesis and the production of myeloid progenitors while reduced the production of erythroidprogenitors, indicating that HOXA9 plays a key role in hematopoiesis and differentiation of hematopoieticlineages. 展开更多
关键词 HEMATOPOIESIS Differentiation of hematopoietic lineages HOXA9 MESODERM Human embryonic stem cells(hESCs) TET-ON Inducible expression system
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