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研究人員｜中央研究院 細胞與個體生物學研究所

研究人員
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側邊選單開關 研究人員
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郭紘志老師實驗室

  • 郭紘志Hung-Chih Kuo
    研究員兼副所長Research Fellow & Deputy Director
    • 專長：Stem Cell Biology, Regenerative Medicine RNA Biology
    • 信箱：kuohuch@gate.sinica.edu.tw
    • 電話：02-2789-9588
    • 位置：N401B/IBMS
友善列印
實驗室簡介展開收合

全能性幹細胞有兩種，一種是由發育中的胚胎所建立而成的胚胎幹細胞，另外一種是由體細胞再編程而建立的誘導性多能幹細胞。全能性幹細胞具有在體外或體內分化成各種細胞的能力，藉此所得分化的細胞可提供做為更新修復受傷或帶有病徵細胞的來源，亦可作為藥物篩選的平台。探討全能性幹細胞內調控自我更新與分化之間的平衡機制對於其應用是相當重要的。然而，雖然全能性幹細胞內的轉錄調控機制日益被了解，轉錄後機制如何去影響細胞的全能性維持與早期譜系分化仍相當未知。轉錄後修飾常常與非編碼RNA相關，而我們最近的研究發現反式剪接RNA在調控全能性幹細胞的全能性有嶄新的機制。為了探討非編碼RNA在細胞與分子的功能，我們整合全系統偵測方式、全能性幹細胞平台與體外分化的實驗。藉此綜合的方法，我們將能探索轉錄後修飾如何調控細胞分化命運以及變異的RNA如何導致人類疾病之謎。

我們實驗室的另外一個研究主軸是探討轉錄因子如何調控全能性幹細胞形成神經外胚層如大腦與脊隨的網絡機制。我們已經成功建立許多體外神經分化的平台，利用這些平台，我們得以探討重要的轉錄因子，如LHX2與SOX2在全能性幹細胞往神經方向分化所扮演的角色。除此之外，我們也利用全能性幹細胞體外形成的立體大腦結構來探討調控早期大腦皮層分化的分子機轉。另外，我們也利用帶有疾病的人類誘導型全能性幹細胞及其分化的神經前驅細胞作為體外研究平台，以期找到新的臨床治療方式。

我們實驗室的研究主要著重於：

  • 環狀RNA與反式剪接RNA在維持全能性、再編程與調控分化的功能
  • 人類全能性細胞進行大腦皮層分化的分子機轉
  • 利用人類誘導型全能性幹細胞以其分化的神經前驅細胞做為平台探討神經退化性疾病
實驗室成員展開收合
姓名 職稱 電話 Email 備註
郭紘志 研究員 02-2789-9580 CC201 kuohuch@gate.sinica.edu.tw
著作展開收合
1
Huang HP, Chiang W, Chuang CY, Stone L, Kang CK, Hwu WL, Kuo HC*. (2019) Using human Pompe Disease induced pluripotent stem cells-derived neural cells for identifying chemicals with therapeutic potential. Molecular Human Genetics (In Press)
2
Yu CY and Kuo HC*. (2019) The emerging roles and function of circular RNAs and their generation. Journal of Biomedical Sciences, 26(1):29
3
Chuang CY, Yang CC, Soong BW, Yu CY, Chen SH, Huang HP, Kuo HC*. (2019) Modeling spinocerebellar ataxias 2 and 3 with iPSCs reveals a role for glutamate in disease pathology. Scientific Reports, 9(1)1166
4
Wu YY, Chiu FL, Yeh CS, Kuo HC*. (2019) Opportunities and challenges of induced pluripotent stem cells in neurodegenerative diseases. Open Biology, 9(1):180177
5
Yu CY, Chuang CY and Kuo HC*. (2018) Trans-spliced long non-coding RNA: an emerging regulator of pluripotency. Cellular and Molecular Life Sciences, 75(18), 3339-3351
6
Yu CY, Li TC, Wu YY, Yeh CH, Chiang W, Chuang CY, Kuo HC*. (2017) The Circular RNA circBIRC6 participates in the molecular circuitry controlling human pluripotency. Nature Communications. 8(1):1149.
7
Lee IH, Huang SS, Chuang CY, Liao KH, Chang LH, Chuang CC, Su YS, Lin HJ, Hsieh JY, Su SH, Lee OK, Kuo HC*. (2017) Delayed epidural transplantation of human induced pluripotent stem cell-derived neural progenitors enhances functional recovery after stroke. Scientific Reports, 7(1):1943.
8
Hou PS, Chuang CY, Yeh CH, Chiang W, Liu HJ, Lin TN, Kuo HC*. (2017) Direct conversion of human fibroblasts into neural progenitors via the use of transcription factors highly enriched in human ESC-derived neural progenitors, Stem Cell Reports. 8(1):54-68.
9
Sudhir P, Kumari MP, Hsu WT, Chen CH, Kuo HC*, Chen CH*. (2016) Integrative omics connects N-glycoproteome-wide alterations with pathways and regulatory events in induced pluripotent stem cells. Scientific Reports. 6:36109.
10
Yu CY and Kuo HC*. (2016) The trans-spliced long noncoding RNA tsRMST impedes human ESC differentiation through WNT5A-mediated inhibition of the epithelial-to-mesenchymal transition, Stem Cells. 34(8):2052-62.
11
Chiu FL, Lin JT, Chuang CY, Chien T, Chen CM, Chen KH, Hsiao HY, Lin YS, Chern Y*, Kuo HC*. (2015) Elucidating the role of the A2A adenosine receptor in neurodegeneration using neurons derived from Huntington’s disease iPSCs”. Human Molecular Genetics. 24(21): 6066-6079.
12
Chuang CY, Huang MC, Chen HF, Tseng LH, Yu CY, Stone L, Huang HP, Ho HN, Kuo HC*. (2015) Granulosa cell-derived induced pluripotent stem cells exhibit pro-trophoblastic differentiation potential . Stem Cell Research & Therapy. 6(1):14-24.
13
Hsu CL, Nam YC, Chang CP, Wang CF, Kuo HC, Touboul JD and Chou SJ. (2015) Lhx2 regulates the timing of β-catenin-dependent cortical neurogenesis, Proceedings of the National Academy of Sciences of the United States of America. 112(39):12199-12204.
14
Hsiao HY, Chen YC, Huang CH, Chen CC, Hsu YH, Chen HM, Chiu FL, Kuo HC, Chen C, Chern Y. (2015) Aberrant astrocytes impair vascular reactivity in Huntington disease, Annals of Neurology. 78(2):178-192.
15
Yu CY, Liu HJ, Kuo HC*, Chuang TJ*. (2014). Is an observed non-co-linear RNA product spliced in trans, in cis, or just in vitro? Nuclei Acids Research. 42(14):9410-23.
16
Wu CS, Yu CY, Chuang CY, Hsiao M, Kao CF, Kuo HC*, Chuang TJ*. (2014) Integrative transcriptome sequencing identifies trans-splicing events with important roles in human embryonic stem cell pluripotency. Genome Research. 24(1):25-36. (Highlighted by Nature Reviews Genetics)
17
Lin YI, Chiu FL, Yeang CH, Chen HF, Chuang CY, Yang SY, Hou PS, Sintupisut N, Ho HN, Kuo HC*, Lin KI*. (2014) Suppression of the SOX2 neural effector gene by PRDM1 promotes human germ cell fate in embryonic stem cells. Stem Cell Reports. 2(2):189-204.
18
 Hou PS, Chuang CY, Kao CF, Chou SJ, Stone L, Ho HN, Chien Cl, Kuo HC*. (2013) LHX2 regulates the neural differentiation of human embryonic stem cells via transcriptional modulation of PAX6 and CER1. Nucleic Acids Research. 41(16):7753-7770.
19
 Sudhir PR, Kumari M, Hsu WT, Massiot J, Chen CH, Kuo HC*, Chen CH*. (2013) Quantitative profiles of protein complexes and their implications for cell reprograming and pluripotency. Journal of Proteome Research. 12(12):5878-90.
20
Shetty AS, Godbole G, Hou PS, Chaudhary R, Monuki ES, Kuo HC, Rema V, Tole S. (2013) Lhx2 regulates a non-autonomous mechanism for barrel formation in the cortex. Proceedings of the National Academy of Sciences of the United States of America. 110(50): E4913-21.
21
Huang HP, Chuang CY, and Kuo HC*. (2012) Induced pluripotent stem cell technology for disease modeling and drug screening with emphasis on lysosomal storage diseases. Stem Cell Research and Therapy. 3(4), 34-44
22
Chuang CY, Lin KI, Hsiao M, Chen HF, Huang YH, Lin SP, Ho HN, Kuo HC*. (2012) Meiotic competent human germ cell-like cells derived from human embryonic stem cells induced by BMP4/WNT3a signaling and OCT4/EpCAM selection. Journal of Biology Chemistry. 287(18), 14389-14401.
23
Huang HP, Chen PH, Hwu WL, Chuang CY, Chien YH, Lee S, Chien CL, Li LT, Chen HF, Ho HN, Chen CH and Kuo HC*. (2011) Pompe disease induced pluripotent stem cells for pathogenesis modeling, drug testing and disease marker identification. Human Molecular Genetics. 20(24), 4851-4864.
24
Huang HP, Chen PH, Yu CY, Chuang CY, Stone L, Hsiao WC, Li CL, Tsai SC, Chen KV, Chen HF, Ho HN, and Kuo HC*. (2011) Epithelial Cell Adhesion Molecule Complex Proteins Promote Transcription Factor-mediated Pluripotency Reprogramming. Journal of Biology Chemistry. 286(38), 33520-33532.
25
Chen HF, Chuang CY, Lee WC, Huang HP, Wu HC, Ho HN, Chen YJ, and Kuo HC*. (2011) Surface marker epithelial cell adhesion molecule and E-cadherin facilitate the identification and selection of induced pluripotent stem cells . Stem Cell Reviews and Reports. 7(3), 722-735.
26
Huang HP, Yu CY, Chen HF, Chen PH, Chuang CY, Lin SJ, Huang ST, Chan WH, Ueng TH, Ho HN, and Kuo HC*. (2010) Factors from human embryonic stem cell-derived fibroblast-like cells promote topology-dependent hepatic differentiation in primate embryonic stem cells and human induced pluripotent stem cells . Journal of Biology Chemistry. 285(43), 33510-33519.
27
Chen HF, Chuang CY, Hsieh YK, Chang HW, Ho HN, Kuo HC*. (2009) Novel human embryonic stem cell autogenetic feeders support undifferentiation of human ES cells in xeno-free culture. Human Reproduction. 24(5), 1114-1125.
28
Kao CF, Chuang CY, Chen CH and Kuo HC*. (2008) Human Pluripotent Stem Cells: Current Status and Future Perspectives. Chinese Journal of Physiology. 51(4), 214-225
29
Kuo HC, Pau KYf, Yeoman RY, Mitalipov SM, Okano H and Wolf DP. (2003) Differentiation of monkey embryonic stem cells into neural lineages. Biology of Reproduction. 68(5), 1727-1735.
30
Kuo HC, Mackie Ogilvie C and Handyside AH. (1998) Chromosomal mosaicism in the human cleavage stage embryos and the accuracy of single cell genetic analysis for preimplantation genetic diagnosis. Journal of Assisted Reproduction and Genetics. 15: 276-280

BOOK CHAPTERS

  1. Mitalipov SM, Kuo HC, Wolf DP. The mammalian blastocysts as an experimental model. In: An atlas of human blastocysts. The Parthenon Publishing Group. New York, NY. Edited by Veeck LL and Zaninovic N. 2003. 231-250

  2. 郭紘志、陳淑華、張為芳、莊靜玉 2008. 第二章: 胚胎幹細胞的鑑定 幹細胞學 幹細胞與組織工程教學資源中心主編.

  3. 郭紘志 第三章：胚胎及誘導式幹細胞  您不可不知道的幹細胞技術 五南出版社 2008初版

  4. 郭紘志     2009.   幹細胞研究新里程：由歐巴馬解除胚胎幹細胞研究禁令談起    經濟部財團法人生物技術中心2009年生物技術產業年鑑

  5. 郭紘志     2010.  誘導式全能性幹細胞應用之現況與前景 經濟部財團法人生物技術中心2010年生物技術產業年鑑