SELECTED PUBLICATIONS

REGIONALLY SPECIFIED HUMAN BRAIN ORGANOIDS

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In this article, we generated the diencephalic orgadnoids that represent the thalamus, namely the human thalamic organoids (hThO). Fusion with cortical organoids reproduced the formation of reciprocal corticothalamic and thalamocortical projections.

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By using human embryonic stem cells (hESCs) with MeCP2 mutations, we tackled the molecular mechanism how MeCP2 regulates the human brain development. Importantly, we discovered that JQ1, a BET protein inhibitor, rescues the molecular, cellular, and physiological impact of MeCP2 mutant cells and animals.

In this article, transgene, ETV2, was introduced in human cortical organoids (hCOs), which produced the functional vascularized structures.

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2023

Female naïve human pluripotent stem cells carry X chromosomes with Xa-like and Xi-like folding conformations. Patterson B, Yang B, Tanaka Y, Kim KY, Cakir B, Xiang Y, Kim J, Wang S, Park IH. Sci Adv. 2023 Aug 4; 2023 Aug 4. PMID: 37540754.

Generation of ventralized human thalamic organoids with thalamic reticular nucleus. Kiral FR, Cakir B, Tanaka Y, Kim J, Yang WS, Wehbe F, Kang YJ, Zhong M, Sancer G, Lee SH, Xiang Y, Park IH. Cell Stem Cell. 2023 Mar 28:S1934-5909(23)00078-4. doi: 10.1016/j.stem.2023.03.007. Online ahead of print.PMID: 37019105

Mutations in the transcriptional regulator MeCP2 severely impact key cellular and molecular signatures of human astrocytes during maturation. Sun J, Osenberg S, Irwin A, Ma LH, Lee N, Xiang Y, Li F, Wan YW, Park IH, Maletic-Savatic M, Ballas N. Cell Rep. 2023 Jan 31; 2023 Jan 5. PMID: 36640327.

2022

Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas. Zhang H, Li B, Huang Q, López-Giráldez F, Tanaka Y, Lin Q, Mehta S, Wang G, Graham M, Liu X, Park IH, Eichmann A, Min W, Zhou JH. Nat Commun. 2022 Dec 10; 2022 Dec 10. PMID: 36496409.

Advanced in vitro models: Microglia in action. Cakir B, Kiral FR, Park IH. Neuron. 2022 Nov 2;110(21):3444-3457. doi: 10.1016/j.neuron.2022.10.004.PMID: 36327894 Review.

natur

A nomenclature consensus for nervous system organoids and assembloids. Pașca SP, Arlotta P, Bateup HS, Camp JG, Cappello S, Gage FH, Knoblich JA, Kriegstein AR, Lancaster MA, Ming GL, Muotri AR, Park IH, Reiner O, Song H, Studer L, Temple S, Testa G, Treutlein B, Vaccarino FM. Nature. 2022 Sep;609(7929):907-910. doi: 10.1038/s41586-022-05219-6. Epub 2022 Sep 28.PMID: 36171373

Dyslexia associated gene KIAA0319 regulates cell cycle during human neuroepithelial cell development. Paniagua S, Cakir B, Hu Y, Kiral FR, Tanaka Y, Xiang Y, Patterson B, Gruen JR, Park IH. Front Cell Dev Biol. 2022 Aug 9;10:967147. doi: 10.3389/fcell.2022.967147. eCollection 2022.PMID: 36016658

Human Down syndrome microglia are up for a synaptic feast. Kiral FR, Park IH. Cell Stem Cell. 2022 Jul 7;29(7):1007-1008. doi: 10.1016/j.stem.2022.06.008.PMID: 35803219

Getting the right cells. Cakir B, Park IH. Elife. 2022 Jun 30;11:e80373. doi: 10.7554/eLife.80373.PMID: 35770899

Live isolation of naïve ESCs via distinct glucose metabolism and stored glycogen. Kim KT, Oh JY, Park S, Kim SM, Benjamin P, Park IH, Chun KH, Chang YT, Cha HJ. Metab Eng. 2022 Mar 10; 2022 Mar 10. PMID: 35283260.

Region Specific Brain Organoids to Study Neurodevelopmental Disorders. Susaimanickam PJ, Kiral FR, Park IH. Int J Stem Cells. 2022 Feb 28. PMID: 35220290.

Expression of the transcription factor PU.1 induces the generation of microglia-like cells in human cortical organoids. Cakir B, Tanaka Y, Kiral FR, Xiang Y, Dagliyan O, Wang J, Lee M, Greaney AM, Yang WS, duBoulay C, Kural MH, Patterson B, Zhong M, Kim J, Bai Y, Min W, Niklason LE, Patra P, Park IH. Nat Commun. 2022 Jan 20;13(1):430. doi: 10.1038/s41467-022-28043-y.

2021

Exploration of alcohol use disorder-associated brain miRNA-mRNA regulatory networks. Lim Y, Beane-Ebel JE, Tanaka Y, Ning B, Husted CR, Henderson DC, Xiang Y, Park IH, Farrer LA, Zhang H.Transl Psychiatry. 2021 Oct 2;11(1):504

Vulnerability of cholecystokinin-expressing GABAergic interneurons in the unilateral intrahippocampal kainate mouse model of temporal lobe epilepsy. Kang YJ, Clement EM, Park IH, Greenfield LJ Jr, Smith BN, Lee SH. Exp Neurol. 2021 Aug PMID: 33915166.

Regeneration of i nfarcted mouse hearts by cardiovascular tissue formed via the direct reprogramming of mouse fibroblasts. Cho J, Kim S, Lee H, Rah W, Cho HC, Kim NK, Bae S, Shin DH, Lee MG, Park IH, Tanaka Y, Shin E, Yi H, Han JW, Hwang PTJ, Jun HW, Park HJ, Cho K, Lee SW, Jung JK, Levit RD, Sussman MA, Harvey RP, Yoon YS.Nat Biomed Eng. 2021 Aug;5(8):880-896

Regional specification and complementation with non-neuroectodermal cells in human brain organoids. Tanaka Y, Park IH. J Mol Med (Berl). 2021 Apr; 2021 Mar 2. PMID: 33651139.

Deconstructing and reconstructing the human brain with regionally specified brain organoids. Xiang Y, Cakir B, Park IH. Semin Cell Dev Biol. 2021 Mar; 2020 Jun 15. PMID: 32553582.

How well do brain organoids capture your brain? Kim J, Sullivan GJ, Park IH. iScience. 2021 Feb 19; 2021 Jan 19. PMID: 33554067.

Genes causing congenital hydrocephalus: Their chromosomal characteristics of telomere proximity and DNA compositions. McKnight I, Hart C, Park IH, Shim JW. Exp Neurol. 2021 Jan; 2020 Nov 4. PMID: 33157092

Reprogramming progressive cells display low CAG promoter activity. Hu X, Wu Q, Zhang J, Kim J, Chen X, Hartman AA, Eastman AE, Park IH, Guo S. Stem Cells. 2021 Jan; 2020 Nov 4. PMID: 33075202.

2020

Intracerebral Transplants of GMP-Grade Human Umbilical Cord-Derived Mesenchymal Stromal Cells Effectively Treat Subacute-Phase Ischemic Stroke in a Rodent Model. Noh JE, Oh SH, Park IH, Song J. Front Cell Neurosci. 2020; 2020 Sep 25. PMID: 33100972.

Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations. Wang K, Zhang H, He Y, Jiang Q, Tanaka Y, Park IH, Pober JS, Min W, Zhou HJ. Arterioscler Thromb Vasc Biol. 2020 Sep; 2020 Jul 9. PMID: 32640906.

Implantation of the clinical-grade human neural stem cell line, CTX0E03, rescues the behavioral and pathological deficits in the quinolinic acid-lesioned rodent model of Huntington's disease. Yoon Y, Kim HS, Jeon I, Noh JE, Park HJ, Lee S, Park IH, Stevanato L, Hicks C, Corteling R, Barker RA, Sinden JD, Song J. Stem Cells. 2020 Aug; 2020 May 6. PMID: 32374064.

Dysregulation of BRD4 Function Underlies the Functional Abnormalities of MeCP2 Mutant Neurons. Xiang Y, Tanaka Y, Patterson B, Hwang SM, Hysolli E, Cakir B, Kim KY, Wang W, Kang YJ, Clement EM, Zhong M, Lee SH, Cho YS, Patra P, Sullivan GJ, Weissman SM, Park IH. Mol Cell. 2020 Jul 2; 2020 Jun 10. PMID: 32526163.

Generation of Regionally Specified Human Brain Organoids Resembling Thalamus Development. Xiang Y, Cakir B, Park IH. STAR Protoc. 2020 Jun 19; 2020 Jun 4. PMID: 33103124.

Synthetic Analyses of Single-Cell Transcriptomes from Multiple Brain Organoids and Fetal Brain. Tanaka Y, Cakir B, Xiang Y, Sullivan GJ, Park IH. Cell Rep. 2020 Feb 11. PMID: 32049002.

The critical role of persistent sodium current in hippocampal gamma oscillations. Kang YJ, Clement EM, Sumsky SL, Xiang Y, Park IH, Santaniello S, Greenfield LJ Jr, Garcia-Rill E, Smith BN, Lee SH. Neuropharmacology. 2020 Jan 1; 2019 Sep 21. PMID: 31550457.

2019

Engineering of human brain organoids with a functional vascular-like system. Cakir B, Xiang Y, Tanaka Y, Kural MH, Parent M, Kang YJ, Chapeton K, Patterson B, Yuan Y, He CS, Raredon MSB, Dengelegi J, Kim KY, Sun P, Zhong M, Lee S, Patra P, Hyder F, Niklason LE, Lee SH, Yoon YS, Park IH. Nat Methods. 2019 Nov; 2019 Oct 7. PMID: 31591580.

The RNA exosome nuclease complex regulates human embryonic stem cell differentiation. Belair C, Sim S, Kim KY, Tanaka Y, Park IH, Wolin SL. J Cell Biol. 2019 Aug 5; 2019 Jul 15. PMID: 31308215.

hESC-Derived Thalamic Organoids Form Reciprocal Projections When Fused with Cortical Organoids. Xiang Y, Tanaka Y, Cakir B, Patterson B, Kim KY, Sun P, Kang YJ, Zhong M, Liu X, Patra P, Lee SH, Weissman SM, Park IH. Cell Stem Cell. 2019 Mar 7; 2019 Feb 21. PMID: 30799279.

2018

Generation and Fusion of Human Cortical and Medial Ganglionic Eminence Brain Organoids. Xiang Y, Yoshiaki T, Patterson B, Cakir B, Kim KY, Cho YS, Park IH. Curr Protoc Stem Cell Biol. 2018 Nov; 2018 Sep 11. PMID: 30854156.

Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a. Kim KY, Tanaka Y, Su J, Cakir B, Xiang Y, Patterson B, Ding J, Jung YW, Kim JH, Hysolli E, Lee H, Dajani R, Kim J, Zhong M, Lee JH, Skalnik D, Lim JM, Sullivan GJ, Wang J, Park IH. Nat Commun. 2018 Jul 3; 2018 Jul 3. PMID: 29968706.

Correction to: New Advances in Human X Chromosome Status from a Developmental and Stem Cell Biology. Patterson B, Tanaka Y, Park IH. Tissue Eng Regen Med. 2018 Feb; 2018 Jan 19. PMID: 30603540.

2017

New Advances in Human X chromosome status from a Developmental and Stem Cell Biology. Patterson B, Tanaka Y, Park IH. Tissue Eng Regen Med. 2017 Dec; 2017 Nov 22. PMID: 29276809.

Enhanced Therapeutic and Long-Term Dynamic Vascularization Effects of Human Pluripotent Stem Cell-Derived Endothelial Cells Encapsulated in a Nanomatrix Gel. Lee SJ, Sohn YD, Andukuri A, Kim S, Byun J, Han JW, Park IH, Jun HW, Yoon YS. Circulation. 2017 Nov 14; 2017 Sep 29. PMID: 28972000.

Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration. Xiang Y, Tanaka Y, Patterson B, Kang YJ, Govindaiah G, Roselaar N, Cakir B, Kim KY, Lombroso AP, Hwang SM, Zhong M, Stanley EG, Elefanty AG, Naegele JR, Lee SH, Weissman SM, Park IH. Cell Stem Cell. 2017 Sep 7; 2017 Jul 27. PMID: 28757360.

Bisulfite-independent analysis of CpG island methylation enables genome-scale stratification of single cells. Han L, Wu HJ, Zhu H, Kim KY, Marjani SL, Riester M, Euskirchen G, Zi X, Yang J, Han J, Snyder M, Park IH, Irizarry R, Weissman SM, Michor F, Fan R, Pan X. Nucleic Acids Res. 2017 Jun 2. PMID: 28126923.

Development of an inducible platform for intercellular protein delivery. Siller R, Dufour E, Lycke M, Wilmut I, Jung YW, Park IH, Sullivan GJ. Int J Pharm. 2017 Apr 30; 2017 Feb 28. PMID: 28254654.

Direct Reprogramming of Human Dermal Fibroblasts Into Endothelial Cells Using ER71/ETV2. Lee S, Park C, Han JW, Kim JY, Cho K, Kim EJ, Kim S, Lee SJ, Oh SY, Tanaka Y, Park IH, An HJ, Shin CM, Sharma S, Yoon YS. Circ Res. 2017 Mar 3; 2016 Dec 21. PMID: 28003219.

Single cell transcriptomics reveals unanticipated features of early hematopoietic precursors. Yang J, Tanaka Y, Seay M, Li Z, Jin J, Garmire LX, Zhu X, Taylor A, Li W, Euskirchen G, Halene S, Kluger Y, Snyder MP, Park IH, Pan X, Weissman SM. Nucleic Acids Res. 2017 Feb 17. PMID: 28003475.

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