PMID- 31959746
OWN - NLM
STAT- MEDLINE
DCOM- 20200505
LR  - 20210119
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 11
IP  - 1
DP  - 2020 Jan 20
TI  - JMJD3 and UTX determine fidelity and lineage specification of human neural 
      progenitor cells.
PG  - 382
LID - 10.1038/s41467-019-14028-x [doi]
LID - 382
AB  - Neurogenesis, a highly orchestrated process, entails the transition from a 
      pluripotent to neural state and involves neural progenitor cells (NPCs) and 
      neuronal/glial subtypes. However, the precise epigenetic mechanisms underlying 
      fate decision remain poorly understood. Here, we delete KDM6s (JMJD3 and/or UTX), 
      the H3K27me3 demethylases, in human embryonic stem cells (hESCs) and show that 
      their deletion does not impede NPC generation from hESCs. However, KDM6-deficient 
      NPCs exhibit poor proliferation and a failure to differentiate into neurons and 
      glia. Mechanistically, both JMJD3 and UTX are found to be enriched in gene loci 
      essential for neural development in hNPCs, and KDM6 impairment leads to H3K27me3 
      accumulation and blockade of DNA accessibility at these genes. Interestingly, 
      forced expression of neuron-specific chromatin remodelling BAF (nBAF) rescues the 
      neuron/glia defect in KDM6-deficient NPCs despite H3K27me3 accumulation. Our 
      findings uncover the differential requirement of KDM6s in specifying NPCs and 
      neurons/glia and highlight the contribution of individual epigenetic regulators 
      in fate decisions in a human development model.
FAU - Shan, Yongli
AU  - Shan Y
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
AD  - University of Chinese Academy of Sciences, Beijing, 100049, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Zhang, Yanqi
AU  - Zhang Y
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - University of Chinese Academy of Sciences, Beijing, 100049, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Zhao, Yuan
AU  - Zhao Y
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - University of Chinese Academy of Sciences, Beijing, 100049, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Wang, Tianyu
AU  - Wang T
AUID- ORCID: 0000-0003-4169-8268
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Zhang, Jingyuan
AU  - Zhang J
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - University of Chinese Academy of Sciences, Beijing, 100049, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Yao, Jiao
AU  - Yao J
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Ma, Ning
AU  - Ma N
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
FAU - Liang, Zechuan
AU  - Liang Z
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Huang, Wenhao
AU  - Huang W
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Huang, Ke
AU  - Huang K
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Zhang, Tian
AU  - Zhang T
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - University of Chinese Academy of Sciences, Beijing, 100049, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Su, Zhenghui
AU  - Su Z
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Chen, Qianyu
AU  - Chen Q
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Zhu, Yanling
AU  - Zhu Y
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - University of Chinese Academy of Sciences, Beijing, 100049, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Wu, Chuman
AU  - Wu C
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Zhou, Tiancheng
AU  - Zhou T
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Sun, Wei
AU  - Sun W
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Wei, Yanxing
AU  - Wei Y
AD  - Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
FAU - Zhang, Cong
AU  - Zhang C
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - University of Chinese Academy of Sciences, Beijing, 100049, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Li, Chenxu
AU  - Li C
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
FAU - Su, Shuquan
AU  - Su S
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
FAU - Liao, Baojian
AU  - Liao B
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Zhong, Mei
AU  - Zhong M
AD  - Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
FAU - Zhong, Xiaofen
AU  - Zhong X
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Nie, Jinfu
AU  - Nie J
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Pei, Duanqing
AU  - Pei D
AUID- ORCID: 0000-0002-5222-014X
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China.
FAU - Pan, Guangjin
AU  - Pan G
AD  - CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, 
      Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 
      Guangzhou Medical University, Guangzhou, 510530, China. pan_guangjin@gibh.ac.cn.
AD  - Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South 
      China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou 
      Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 
      510530, China. pan_guangjin@gibh.ac.cn.
AD  - Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 
      510005, China. pan_guangjin@gibh.ac.cn.
AD  - Shandong Medicinal Biotechnology Center, Shandong First Medical University & 
      Shandong Academy of Medical Sciences, Jinan, 250012, China. 
      pan_guangjin@gibh.ac.cn.
AD  - Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and 
      Innovation, Chinese Academy of Sciences, Hong Kong, China. 
      pan_guangjin@gibh.ac.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200120
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (BANF1 protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Histones)
RN  - EC 1.14.11.- (Histone Demethylases)
RN  - EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases)
RN  - EC 1.14.11.- (KDM6A protein, human)
RN  - EC 1.14.11.- (KDM6B protein, human)
SB  - IM
MH  - Cell Differentiation/*genetics
MH  - Cell Line
MH  - Cell Proliferation/genetics
MH  - DNA Methylation
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Embryonic Stem Cells/physiology
MH  - Epigenesis, Genetic/physiology
MH  - *Gene Expression Regulation, Developmental
MH  - Gene Knock-In Techniques
MH  - Gene Knockout Techniques
MH  - Histone Demethylases/genetics/*metabolism
MH  - Histones/genetics/metabolism
MH  - Humans
MH  - Jumonji Domain-Containing Histone Demethylases/genetics/*metabolism
MH  - Neural Stem Cells/*physiology
MH  - Neurogenesis/genetics
MH  - RNA-Seq
PMC - PMC6971254
COIS- The authors declare no competing interests.
EDAT- 2020/01/22 06:00
MHDA- 2020/05/06 06:00
PMCR- 2020/01/20
CRDT- 2020/01/22 06:00
PHST- 2018/09/12 00:00 [received]
PHST- 2019/12/13 00:00 [accepted]
PHST- 2020/01/22 06:00 [entrez]
PHST- 2020/01/22 06:00 [pubmed]
PHST- 2020/05/06 06:00 [medline]
PHST- 2020/01/20 00:00 [pmc-release]
AID - 10.1038/s41467-019-14028-x [pii]
AID - 14028 [pii]
AID - 10.1038/s41467-019-14028-x [doi]
PST - epublish
SO  - Nat Commun. 2020 Jan 20;11(1):382. doi: 10.1038/s41467-019-14028-x.