Actl6a protects embryonic stem cells from differentiating into primitive endoderm. 2015

Weisi Lu, and Lekun Fang, and Bin Ouyang, and Xiya Zhang, and Shaoquan Zhan, and Xuyang Feng, and Yaofu Bai, and Xin Han, and Hyeung Kim, and Quanyuan He, and Ma Wan, and Feng-Tao Shi, and Xin-Hua Feng, and Dan Liu, and Junjiu Huang, and Zhou Songyang
Key Laboratory of Gene Engineering of the Ministry of Education, Institute of Healthy Aging Research and SYSU-BCM Joint Research Center, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

Actl6a (actin-like protein 6A, also known as Baf53a or Arp4) is a subunit shared by multiple complexes including esBAF, INO80, and Tip60-p400, whose main components (Brg1, Ino80, and p400, respectively) are crucial for the maintenance of embryonic stem cells (ESCs). However, whether and how Actl6a functions in ESCs has not been investigated. ESCs originate from the epiblast (EPI) that is derived from the inner cell mass (ICM) in blastocysts, which also give rise to primitive endoderm (PrE). The molecular mechanisms for EPI/PrE specification remain unclear. In this study, we provide the first evidence that Actl6a can protect mouse ESCs (mESCs) from differentiating into PrE. While RNAi knockdown of Actl6a, which appeared highly expressed in mESCs and downregulated during differentiation, induced mESCs to differentiate towards the PrE lineage, ectopic expression of Actl6a was able to repress PrE differentiation. Our work also revealed that Actl6a could interact with Nanog and Sox2 and promote Nanog binding to pluripotency genes such as Oct4 and Sox2. Interestingly, cells depleted of p400, but not of Brg1 or Ino80, displayed similar PrE differentiation patterns. Mutant Actl6a with impaired ability to bind Tip60 and p400 failed to block PrE differentiation induced by Actl6a dysfunction. Finally, we showed that Actl6a could target to the promoters of key PrE regulators (e.g., Sall4 and Fgf4), repressing their expression and inhibiting PrE differentiation. Our findings uncover a novel function of Actl6a in mESCs, where it acts as a gatekeeper to prevent mESCs from entering into the PrE lineage through a Yin/Yang regulating pattern.

UI MeSH Term Description Entries
D001755 Blastocyst A post-MORULA preimplantation mammalian embryo that develops from a 32-cell stage into a fluid-filled hollow ball of over a hundred cells. A blastocyst has two distinctive tissues. The outer layer of trophoblasts gives rise to extra-embryonic tissues. The inner cell mass gives rise to the embryonic disc and eventual embryo proper. Embryo, Preimplantation,Blastocysts,Embryos, Preimplantation,Preimplantation Embryo,Preimplantation Embryos
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002868 Chromosomal Proteins, Non-Histone Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens. Non-Histone Chromosomal Proteins,Chromosomal Proteins, Non Histone,Chromosomal Proteins, Nonhistone,Non-Histone Chromosomal Phosphoproteins,Chromosomal Phosphoproteins, Non-Histone,Non Histone Chromosomal Phosphoproteins,Non Histone Chromosomal Proteins,Nonhistone Chromosomal Proteins,Proteins, Non-Histone Chromosomal
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D004707 Endoderm The inner of the three germ layers of an embryo. Definitive Endoderm,Definitive Endoderms,Endoderm, Definitive,Endoderms
D005855 Germ Layers The three primary germinal layers (ECTODERM; ENDODERM; and MESODERM) developed during GASTRULATION that provide tissues and body plan of a mature organism. They derive from two early layers, hypoblast and epiblast. Epiblast,Hypoblast,Epiblasts,Germ Layer,Hypoblasts,Layer, Germ,Layers, Germ
D000066450 Mouse Embryonic Stem Cells PLURIPOTENT STEM CELLS derived from the BLASTOCYST INNER CELL MASS of day 3.5 mouse embryos. mESC,Cells, Mouse Embryonic Stem,Mouse Embryonic Stem Cell,Stem Cells, Mouse Embryonic,mESCs
D000199 Actins Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle. F-Actin,G-Actin,Actin,Isoactin,N-Actin,alpha-Actin,alpha-Isoactin,beta-Actin,gamma-Actin,F Actin,G Actin,N Actin,alpha Actin,alpha Isoactin,beta Actin,gamma Actin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D050814 Octamer Transcription Factor-3 An octamer transcription factor that is expressed primarily in totipotent embryonic STEM CELLS and GERM CELLS and is down-regulated during CELL DIFFERENTIATION. Oct-3 Transcription Factor,Transcription Factor Oct-3,Oct-4 Transcription Factor,Octamer-Binding Protein 4,POU Domain, Class 5, Transcription Factor 1,POU5F1 Transcription Factor,Transcription Factor Oct-4,Oct 3 Transcription Factor,Oct 4 Transcription Factor,Oct-3, Transcription Factor,Oct-4, Transcription Factor,Octamer Binding Protein 4,Octamer Transcription Factor 3,Transcription Factor Oct 3,Transcription Factor Oct 4,Transcription Factor, Oct-3,Transcription Factor, Oct-4,Transcription Factor, POU5F1,Transcription Factor-3, Octamer

Related Publications

Weisi Lu, and Lekun Fang, and Bin Ouyang, and Xiya Zhang, and Shaoquan Zhan, and Xuyang Feng, and Yaofu Bai, and Xin Han, and Hyeung Kim, and Quanyuan He, and Ma Wan, and Feng-Tao Shi, and Xin-Hua Feng, and Dan Liu, and Junjiu Huang, and Zhou Songyang
October 2016, eLife,
Weisi Lu, and Lekun Fang, and Bin Ouyang, and Xiya Zhang, and Shaoquan Zhan, and Xuyang Feng, and Yaofu Bai, and Xin Han, and Hyeung Kim, and Quanyuan He, and Ma Wan, and Feng-Tao Shi, and Xin-Hua Feng, and Dan Liu, and Junjiu Huang, and Zhou Songyang
June 2011, International journal of stem cells,
Weisi Lu, and Lekun Fang, and Bin Ouyang, and Xiya Zhang, and Shaoquan Zhan, and Xuyang Feng, and Yaofu Bai, and Xin Han, and Hyeung Kim, and Quanyuan He, and Ma Wan, and Feng-Tao Shi, and Xin-Hua Feng, and Dan Liu, and Junjiu Huang, and Zhou Songyang
January 2009, Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery,
Weisi Lu, and Lekun Fang, and Bin Ouyang, and Xiya Zhang, and Shaoquan Zhan, and Xuyang Feng, and Yaofu Bai, and Xin Han, and Hyeung Kim, and Quanyuan He, and Ma Wan, and Feng-Tao Shi, and Xin-Hua Feng, and Dan Liu, and Junjiu Huang, and Zhou Songyang
September 2008, Development, growth & differentiation,
Weisi Lu, and Lekun Fang, and Bin Ouyang, and Xiya Zhang, and Shaoquan Zhan, and Xuyang Feng, and Yaofu Bai, and Xin Han, and Hyeung Kim, and Quanyuan He, and Ma Wan, and Feng-Tao Shi, and Xin-Hua Feng, and Dan Liu, and Junjiu Huang, and Zhou Songyang
July 2010, Stem cells and development,
Weisi Lu, and Lekun Fang, and Bin Ouyang, and Xiya Zhang, and Shaoquan Zhan, and Xuyang Feng, and Yaofu Bai, and Xin Han, and Hyeung Kim, and Quanyuan He, and Ma Wan, and Feng-Tao Shi, and Xin-Hua Feng, and Dan Liu, and Junjiu Huang, and Zhou Songyang
January 2004, Methods in molecular biology (Clifton, N.J.),
Weisi Lu, and Lekun Fang, and Bin Ouyang, and Xiya Zhang, and Shaoquan Zhan, and Xuyang Feng, and Yaofu Bai, and Xin Han, and Hyeung Kim, and Quanyuan He, and Ma Wan, and Feng-Tao Shi, and Xin-Hua Feng, and Dan Liu, and Junjiu Huang, and Zhou Songyang
December 2008, Cloning and stem cells,
Weisi Lu, and Lekun Fang, and Bin Ouyang, and Xiya Zhang, and Shaoquan Zhan, and Xuyang Feng, and Yaofu Bai, and Xin Han, and Hyeung Kim, and Quanyuan He, and Ma Wan, and Feng-Tao Shi, and Xin-Hua Feng, and Dan Liu, and Junjiu Huang, and Zhou Songyang
November 2004, Journal of cell science,
Weisi Lu, and Lekun Fang, and Bin Ouyang, and Xiya Zhang, and Shaoquan Zhan, and Xuyang Feng, and Yaofu Bai, and Xin Han, and Hyeung Kim, and Quanyuan He, and Ma Wan, and Feng-Tao Shi, and Xin-Hua Feng, and Dan Liu, and Junjiu Huang, and Zhou Songyang
July 2009, Current protocols in stem cell biology,
Weisi Lu, and Lekun Fang, and Bin Ouyang, and Xiya Zhang, and Shaoquan Zhan, and Xuyang Feng, and Yaofu Bai, and Xin Han, and Hyeung Kim, and Quanyuan He, and Ma Wan, and Feng-Tao Shi, and Xin-Hua Feng, and Dan Liu, and Junjiu Huang, and Zhou Songyang
February 2005, Diabetes,
Copied contents to your clipboard!