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Hung-Chih Kuo's Lab｜Institute of Cellular and Organismic Biology, Academia Sinica

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Hung-Chih Kuo's Lab

  • Hung-Chih Kuo
    Research Fellow & Deputy Director
    • SpecialtyStem Cell Biology Regenerative Medicine RNA Biology
    • E-mailkuohuch@gate.sinica.edu.tw
    • Tel02-2789-9588
    • LabN401B/IBMS
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Lab IntroductionOpenClose

Pluripotent stem cells (PSC) are established from developing embryos (embryonic stem cells, ESCs) or reprogrammed from somatic cells (induced pluripotent stem cells, iPSC) and remain to differentiate into many cell types in vitro and in vivo allowing the supply of somatic cell types to replace, restore and regenerate dead, damaged or diseased cells and drug screening. Dissecting the regulatory pathways controlling the balance between self-renewal and differentiation is fundamental to the application of PSCs. While transcriptional regulation of PSC is increasingly understood, little is known about how post-transcriptional mechanisms can influence pluripotency maintenance and early lineage differentiation. Post-transcriptional modifications are commonly found in non-coding RNA species and our recent studies identified trans-spliced RNA as a novel mechanism regulating pluripotency. To dissect the cellular and molecular functions of non-colinear RNAs, we are using a combination of system-wide approaches, PSC models and in vitro differentiation assays. Our comprehensive approach will answer how post-transcriptional modification control cell fate specification in normal tissues and how aberrant RNA pathways can cause human diseases.

Another main focus of our laboratory consists in defining the network of transcription factors controlling the differentiation of pluripotent cells into neuroectoderm from which key organs such as brain and spinal cord are derived. Our group has developed protocols to generate various neural cell types form hESCs and hiPSCs. Using these, we are studying the function of key transcription factors involved in the transition between the pluripotent state and the neuroectodermal state such as LHX2, SOX2, and others. We are also investing the molecular function of new regulators controlling early cortical development using 3-D brain structures generate from PSCs. In addition, we are developing in vitro model to study neurodegenerative diseases using hiPSCs and induced neural progenitors derived from patients with brain diseases in hope to identify new medical intervention. The major research interests are listed as follows:

  • Functional roles of the circular and trans-spliced RNAs in pluripotency maintenance, reprogramming, and lineage differentiation.
  • The molecular basis of human pluripotent stem cell cortical differentiation and patterning.
  • Human induced pluripotent stem cells (hiPSC) and induced neural progenitors as therapeutic platforms for neurodegenerative diseases.
Lab MemberOpenClose
Name Job Title Telephone Email Remark
Hung-Chih Kuo Research Fellow 02-2789-9580CC201 kuohuch@gate.sinica.edu.tw
PublicationOpenClose
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