Member: Center for Complex Biological Systems, Institute for Genomics and Bioinformatics, UCI Cancer Center
Pioneer transcription factors, Endoderm development, Genomics, Gene regulatory networks, Zygotic genome activation, Super-enhancers, Preimplantation mammalian development, Fluorescent lifetime imaging
Pioneer transcription factor binding surrounding a super enhancer (SE)
Transcriptomics and Epigenomics
- Zygotic genome activation is a critical period in metazoan development whereby the control of cell fates is transferred from maternal genes to zygotic genes. We examine how the interplay between maternal pioneer transcription factors and epigenetics play during zygotic genome activation, which later results in the establishment of novel specific subsets of enhancers called super enhancers that serve as key nodes regulating cell identity.
- Understanding gene regulatory network architecture would enable identification of components that, when mutated, cause significant phenotypic changes, which has disease implications. We analyze multi-dimensional genomic data sets originating from RNA-seq, ChIP-seq and ATAC-seq, and perform computational network modeling to infer the endoderm gene regulatory network.
- Many human diseases are linked to mutations of cis-regulatory modules (CRMs) that interact with transcription factors. However, there is not a systematic, large-scale approach to uncover enhancer activities during animal development. We apply STARR-seq genome-wide quantitative enhancer discovery approach to determine “functional” CRMs in a direct, quantitative, and genome-wide manner.
scRNA-seq analysis of differentiating endodermal cells
Live Imaging and Modeling of Mammalian Embryos
- Instead of assessing the embryo quality by the standard morphologic evaluation, we adopted the phasor-FLIM (Fluorescence Lifetime Imaging Microscopy) method, which is a non-invasive live imaging approach to capture endogenous autofluorescent metabolic markers to distinguish the quality of pre-implantation embryos.
- We map and quantitate the dynamic activities of TGF-b signaling activities in preimplantation mouse embryos and uncover the biological function and mechanism of TGF-b signaling in the preimplantation mammalian embryos.
- We combine modeling and experimentation to develop a stochastic modeling platform that 1) describes developmental processes occurring on a range of different biological scales, and 2) incorporate data on both mouse and human development to predict the outcome of physical and chemical manipulations of the embryo.
- The CRISPR/Cas9 system offers a significant advantage over other systems for examining mutations in the F0 generation in non-mammalian systems. We useXenopus tropicalis to develop methods to eliminate a large genomic region and induce a homologous recombination at a desired locus within the genome.
Leapfrogging method: Scheme for transplanting Primordial Germ Cells (PGCs) from CRISPR/Cas9-mutagenized blastula stage embryos (bottom) Ito a wild type some (top) that has had its PGC removed. Leapfrogging provides not only a means to overcoming somatic lethal mutations, but also a new method for studying maternal effect genes
Updated (July 2019)
Total Peer Reviewed Publication: 105 papers
i10 index 74
- Paraiso, K.,, Blitz, I.L., Coley, M., Cheung, J., Sudou, N., Taira, M.,Cho, K.W. (2019) Endodermal maternal transcription factors establish super enhancers prior to zygotic genome activation. Cell Reports, 27:2962-2977 PMID: 31167141
- Paraiso, K.,, Blitz, I.L., Zhou, J.J., Cho, KW.Y. (2019). Morpholino antisense oligonucleotides do not elicit induction of a general innate immune response in early Xenopus. Developmental Cell, 49:643-650. PMID: 31112700.
- Ma, N.#, de Mochel, N.R.#, Pham, P.#, Yoon, Y., Cho, K.W.Y.*, Digman, M.* (2019). Label-free assessment of pre-implantation embryo quality by the Fluorescence Lifetime Imaging Microscopy (FLIM)-phasor approach. Scientific Reports, In press. #Shared first authors, *Shared senior authors.
- Gilchrist, ML., Cho, KWY. Veenstra. GJC. (2019). An introduction to genomics protocols for Xenopus. Xenopus Laboratory Manual, Cold Spring Harbor Press. In press.
- Gilchrist, ML., Veenstra. GJC., Cho, KWY. (2019). An introduction to transcriptomics and proteomics. Xenopus Laboratory Manual, Cold Spring Harbor Press. In press.
- Ma, N., de Mochel, N.R., Pham, P., Yoon, Y., Cho, K.W.Y., Digman, M. (2018). Label-free assessment of pre-implantation embryo quality by the Fluorescence Lifetime Imaging Microscopy (FLIM)-phasor approach. bioRxiv 286682; doi: https://doi.org/10.1101/286682
- Jin S Cho, Ira L. Blitz and Ken W.Y. Cho, (2018). DNase-seq to study chromatin accessibility in early Xenopus tropicalis. Chapter 14, Xenopus Laboratory Manual, Cold Spring Habor Press, Cold Spring Harb Protoc. doi: 10.1101/pdb.prot098335.
- Charney RM, Paraiso KD, Blitz IL, Cho KWY. (2017). A gene regulatory program controlling early Xenopus mesendoderm formation: Network conservation and motifs. Semin Cell Dev Biol. 66:12-24.
- Blitz, I.L., Paraiso, K.D., Patrushev, I., Chiu, W.T.Y., Cho, K.W.Y*., Gilchrist,M.J.* (2017). . *contributed equally, co-senior authors. A catalog of Xenopus tropicalis transcription factors and their regional expression in the early gastrula stage embryo. Dev Biol, S0012-1606(16)30118-X. PMID: 27475627.
- Charney, R.M., Forouzmand, E., Cho, J.S., Cheung, J., Paraiso, K.D., Yasuoka, Y., Takahashi, S., Taira, M., Blitz, I.L., Xie, X. and. Cho K.W.Y. (2017). Foxh1 occupies cis-regulatory modules prior to dynamic transcription factor interactions controlling the mesendoderm gene program. Developmental Cell. 40:1-13. (PMID:28325473).
- Holmes, W.R., Mochel, S., Wang, Q., Du, H., Cinquin, O., Cho, K.W*., Nie, Q*. *contributed equally, co-senior authors. (2017). Intracellular noise aids construction of early embryonic structures.. PLoS Comput Biol. 13(1):e1005320
- Forouzmand, E., Owens, N.D.L., Blitz, I.L., Paraiso, K.D., Khokha, M.K., Gilchrist, M.J., Xie X., Cho, K.W.Y. (2016). Developmentally regulated long non-coding RNAs in Xenopus tropicalis. Dev Biol. S0012-1606: 30120-8. PMID: 27418388
- Blitz, I.L., Fish, M.B., and Cho, K.W.Y. (2016). Leapfrogging: Primordial Germ Cell Transplantation Permits Recovery of CRISPR/Cas9-Induced Mutations in Essential Genes. Development, 143:2868-75. PMID: 27385011
- Owens, N.D.L. 1, Blitz, I.L. 1, Lane, M.A., Overton, J.D., Gilchrist, M.J#, Cho, K.W.Y#., Khokha, M.K. # (2016). Embryogenesis kinetics measured by high-resolution absolute quantitation of transcripts. Submitted. 1: co-first authros, # contributed equally. Cell Reports.14, 632-647.
- Chiang, M., Hallman, S., Cinquin, A., Reyes de Mochel, N., Paz, A., Kawauchi, S., Calof, A., Cho, KWY., Fowlkes, C.C., & Cinquin, O. (2015). Analysis of in vivo single cell behavior by high throughput, human-in-the-loop segmentation of three-dimensional images. BMC Bioinformatics. DOI 10.1186/s12859-015-0814-7
- Wang, X., Hsi, H., Guerrero-Juarez, CF., Pham, K., Cho, K., Monuki, ES, Cho, KWY., Gay, DL., Plikus, (2015). Principles and mechanisms of regeneration in the mouse model for wound-induced hair follicle neogenesis. Regeneration. doi: 10.1002/reg2.38.
- Reyes de Mochel, NS., Luong, M., Chiang, M., Javier, A.L., Luu, E., Cinquin, O., and Cho, KWY. (2015). BMP signaling regulates both cell proliferation and ICM lineage commitment in preimplantation-stage mouse embryos. Dev Biol. 397, 45-55.
- Yang, G., Yuan, G., Cho, K.W.Y., and Chen, Y. (2014). An atypical canonical BMP signaling pathway regulates Msx1 expression during odontogenesis. J Biol Chem. 289, 31492-31502.
- Chiu, WT., Le, R., Beisinger, J., Blitz, IL., Xie, X., Cho, KWY. (2014). Comprehensive genomic view of Foxh1 and Smad2/3 interaction in mesendoderm development. Development, 141, 4537-4547.
- Nakayama, T., Blitz I.L., Fish, M.B., Sumanth, A., Cho, K.W.Y., Grainger R. (2014). Cas9-based genome editing in Xenopus tropicalis. Methods in Enzymology, 546, 355-375.
- Yasuoka, Y., Suzuki, Y., Takahashi, S., Sudou, N., Haramoto, Y., Cho, KW., Asashima, M., Sugano, S., and Taira, M. (2014). Otx2 and TLE/Groucho occupancy marks tissue-specific cis-regulatory modules for head specification. Nature Communiations, 9:4322.
- Blitz, IL., Luong, M., Chu, W. and Cho, K.W. (2014). Application of genomic approaches to developmental biology (book chapter for Principal of Developmental Genetics, 2nd edition. Edited by Sally Moody). 37-48.
- Zheng, Z., Christley, S., Chiu, WT., Blitz, IL., Xie, X., Cho, KWY., Nie, Q. (2014) Inference of the Xenopus tropicalis embryonic regulatory network and spatial gene expression patterns. BMS Systems Biology. BMC Syst Biol. 8:3