八聚体结合转录因子4在哺乳动物早期胚胎发育中的研究进展

doi:10.16431/j.cnki.1671-7236.2021.10.023

摘要/Abstract

摘要： 八聚体结合转录因子4（octamer-binding transcription factor 4，OCT4）属于POU （Pit-Oct-Unc）转录因子，在早期胚胎、胚胎干细胞及生殖细胞中特异性表达。由于胚胎干细胞与生殖细胞均来自早期胚胎，尤其是内细胞团（inner cell mass，ICM）细胞，而OCT4作为核心发育因子参与协调早期胚胎全能性的维持和ICM的形成。OCT4和尾型同源盒转录因子2（caudal type homeobox transcription factor 2，CDX2）在小鼠早期胚胎细胞中互斥性表达对于ICM和滋养层（trophectoderm，TE）分化具有重要作用，在囊胚中OCT4特异性表达于ICM，而CDX2特异性表达于TE。但在以猪为代表的其他大型哺乳动物，OCT4持续在囊胚TE中表达，表明OCT4在具有高度保守性的同时还有一定的物种特异性。研究OCT4在哺乳动物早期胚胎发育中的表达规律与调控机理对于了解胚胎干细胞的多能性及其维持也具有十分重要的意义。文章总结了哺乳动物早期胚胎发育中OCT4的表达规律和表达调控机制，以期为深入理解哺乳动物早期胚胎发育调控机制提供参考。

关键词: OCT4; 早期胚胎发育; 哺乳动物; 物种特异性

Abstract: Octamer-binding transcription factor 4 (OCT4) is a POU-family transcription factor, which is specifically expressed in early embryos, embryonic stem cells and germ cells. Since both embryonic stem cells and germ cells come from early embryos, especially inner cell mass (ICM) cells, OCT4 as a core development factor is involved in coordinating the maintenance of early embryo pluripotency and the formation of ICM. The exclusively expression of OCT4 and caudal type homeobox transcription factor 2 (CDX2) in mouse embryonic cells is crucial for ICM and trophectoderm (TE) differentiation and results in OCT4 specially expressed in ICM and CDX2 specially expressed in TE. However, in other large mammals represented by pigs, OCT4 continues to be expressed in blastocyst TE, indicating that OCT4 is highly conserved and has a certain species specificity. Researching the expression and regulation mechanism of OCT4 in early embryonic development of mammals is significant for us to understand the pluripotency and maintenance of embryonic stem cells. This review summarized the expression rules and expression regulation mechanism of OCT4 in mammalian early embryonic development, hoping to provide a reference for in-depth comprehending of mammalian early embryonic development regulation.

Key words: OCT4; early embryonic development; mammal; species specificity

中图分类号:

Q813.7

齐子成, 刘忠华. 八聚体结合转录因子4在哺乳动物早期胚胎发育中的研究进展[J]. 中国畜牧兽医, 2021, 48(10): 3715-3725.

QI Zicheng, LIU Zhonghua. Research Advances on OCT4 in Mammalian Early Embryonic Development[J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(10): 3715-3725.

参考文献

[1] PRATT H P, ZIOMEK C A, REEVE W J, et al.Compaction of the mouse embryo:An analysis of its components[J]. Journal of Embryology and Experimental Morphology, 1982, 70:113-132.
[2] JOHNSON M H, ZIOMEK C A.Induction of polarity in mouse 8-cell blastomeres:Specificity, geometry, and stability[J]. Journal of Cell Biology, 1981, 91(1):303-308.
[3] MATRE J L, TURLIER H, ILLUKKUMBURA R, et al.Asymmetric division of contractile domains couples cell positioning and fate specification[J]. Nature, 2016, 536(7616):344-348.
[4] NISHIOKA N, INOUE K, ADACHI K, et al.The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass[J]. Developmental Cell, 2009, 16(3):398-410.
[5] RALSTON A, COX B J, NISHIOKA N, et al.Gata3 regulates trophoblast development downstream of Tead4 and in parallel to Cdx2[J]. Development, 2010, 137(3):395-403.
[6] CHAZAUD C, YAMANAKA Y, PAWSON T, et al.Early lineage segregation between epiblast and primitive endoderm in mouse blastocysts through the Grb2-MAPK pathway[J]. Developmental Cell, 2006, 10(5):615-624.
[7] GUO G, HUSS M, TONG G Q, et al.Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst[J]. Developmental Cell, 2010, 18(4):675-685.
[8] KURIMOTO K, YABUTA Y, OHINATA Y, et al.An improved single-cell cDNA amplification method for efficient high-density oligonucleotide microarray analysis[J]. Nucleic Acids Research, 2006, 34(5):e42.
[9] SAIZ N, WILLIAMS K M, SESHAN V E, et al.Asynchronous fate decisions by single cells collectively ensure consistent lineage composition in the mouse blastocyst[J]. Nature Communications, 2016, 7:13463.
[10] POSFAI E, PETROPOULOS S, DE BARROS F R O, et al.Position- and Hippo signaling-dependent plasticity during lineage segregation in the early mouse embryo[J]. eLife, 2017, 6:e22906.
[11] BERG D K, SMITH C S, PEARTON D J, et al.Trophectoderm lineage determination in cattle[J]. Developmental Cell, 2011, 20(2):244-255.
[12] DE PAEPE C, CAUFFMAN G, VERLOES A, et al.Human trophectoderm cells are not yet committed[J]. Human Reproduction, 2013, 28(3):740-749.
[13] SCHÖLER H R, HATZOPOULOS A K, BALLING R, et al.A family of octamer-specific proteins present during mouse embryogenesis:Evidence for germline-specific expression of an Oct factor[J]. The EMBO Journal, 1989, 8(9):2543-2550.
[14] YEOM Y I, FUHRMANN G, OVITT C E, et al.Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells[J]. Development, 1996, 122(3):881-894.
[15] NORDHOFF V, HUBNER K, BAUER A, et al.Comparative analysis of human, bovine, and murine Oct-4 upstream promoter sequences[J]. Mammalain Genome, 2001, 12(4):309-317.
[16] DAVIS R L, CHENG P F, LASSAR A B, et al.The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation[J]. Cell, 1990, 60(5):733-746.
[17] SCHOLER H R, RUPPERT S, SUZUKI N, et al.New type of POU domain in germ line-specific protein Oct-4[J]. Nature, 1990, 344(6265):435-439.
[18] LEE T I, JENNER R G, BOYER L A, et al.Control of developmental regulators by Polycomb in human embryonic stem cells[J]. Cell, 2006, 125(2):301-313.
[19] BABAIE Y, HERWIG R, GREBER B, et al.Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells[J]. Stem Cells, 2007, 25(2):500-510.
[20] NICHOLS J, ZEVNIK B, ANASTASSIADIS K, et al.Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4[J]. Cell, 1998, 95(3):379-391.
[21] CAUFFMAN G, LIEBAERS I, VAN STEIRTEGHEM A, et al.POU5F1 isoforms show different expression patterns in human embryonic stem cells and preimplantation embryos[J]. Stem Cells, 2006, 24(12):2685-2691.
[22] LEE J, KIM H K, RHO J Y, et al.The human OCT-4 isoforms differ in their ability to confer self-renewal[J]. Journal of Biological Chemistry, 2006, 281(44):33554-33565.
[23] GUO C L, LIU L, JIA Y D, et al.A novel variant of Oct3/4 gene in mouse embryonic stem cells[J]. Stem Cell Research, 2012, 9(2):69-76.
[24] MIZUNO N, KOSAKA M.Novel variants of Oct-3/4 gene expressed in mouse somatic cells[J]. Journal of Biological Chemistry, 2008, 283(45):30997-31004.
[25] WANG X, DAI J.Concise review:Isoforms of OCT4 contribute to the confusing diversity in stem cell biology[J]. Stem Cells, 2010, 28(5):885-893.
[26] HWANG J Y, OH J N, LEE D K, et al.Identification and differential expression patterns of porcine OCT4 variants[J]. Reproduction, 2015, 149(1):55-66.
[27] OKAZAWA H, OKAMOTO K, ISHINO F, et al.The oct3 gene, a gene for an embryonic transcription factor, is controlled by a retinoic acid repressible enhancer[J]. The EMBO Journal, 1991, 10(10):2997-3005.
[28] TAKEDA J, SEINO S, BELL G I.Human Oct3 gene family:cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues[J]. Nucleic Acids Research, 1992, 20(17):4613-4620.
[29] KIRCHHOF N, CARNWATH J W, LEMME E, et al.Expression pattern of Oct-4 in preimplantation embryos of different species[J]. Biology of Reproduction, 2000, 63(6):1698-1705.
[30] KIM S H, CHOI K H, LEE D K, et al.Identification and characterization of the OCT4 upstream regulatory region in Sus scrofa[J]. Stem Cells International, 2019, 2019:2130973.
[31] ROSNER M H, VIGANO M A, OZATO K, et al.A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo[J]. Nature, 1990, 345(6277):686-692.
[32] SCHOLER H R, DRESSLER G R, BALLING R, et al.Oct-4:A germline-specific transcription factor mapping to the mouse t-complex[J]. The EMBO Journal, 1990, 9(7):2185-2195.
[33] PLACHTA N, BOLLENBACH T, PEASE S, et al.Oct4 kinetics predict cell lineage patterning in the early mammalian embryo[J]. Nature Cell Biology, 2011, 13(2):117-123.
[34] JERABEK S, MERINO F, SCHOLER H R, et al.OCT4:Dynamic DNA binding pioneers stem cell pluripotency[J]. Biochimica et Biophysica Acta, 2014, 1839(3):138-154.
[35] PESCE M, SCHOLER H R.Oct-4:Gatekeeper in the beginnings of mammalian development[J]. Stem Cells, 2001, 19(4):271-278.
[36] PALMIERI S L, PETER W, HESS H, et al.Oct-4 transcription factor is differentially expressed in the mouse embryo during establishment of the first two extraembryonic cell lineages involved in implantation[J]. Developmantal Biology, 1994, 166(1):259-267.
[37] KUIJK E W, DU PUY L, VAN TOL H T, et al.Differences in early lineage segregation between mammals[J]. Developmental Dynamics, 2008, 237(4):918-927.
[38] CAUFFMAN G, VAN DE VELDE H, LIEBAERS I, et al.Oct-4 mRNA and protein expression during human preimplantation development[J]. Molecular Human Reproduction, 2005, 11(3):173-181.
[39] HAMBILIKI F, STROM S, ZHANG P, et al.Co-localization of NANOG and OCT4 in human pre-implantation embryos and in human embryonic stem cells[J]. Journal of Assisted Reproduction and Genetics, 2012, 29(10):1021-1028.
[40] SCHULTZ R M.Regulation of zygotic gene activation in the mouse[J]. Bioessays, 1993, 15(8):531-538.
[41] LI L, ZHENG P, DEAN J.Maternal control of early mouse development[J]. Development, 2010, 137(6):859-870.
[42] WU G, HAN D, GONG Y, et al.Establishment of totipotency does not depend on Oct4A[J]. Nature Cell Biology, 2013, 15(9):1089-1097.
[43] FRUM T, HALBISEN M A, WANG C, et al.Oct4 cell-autonomously promotes primitive endoderm development in the mouse blastocyst[J]. Developmental Cell, 2013, 25(6):610-622.
[44] GAO L, WU K, LIU Z, et al.Chromatin accessibility landscape in human early embryos and its association with evolution[J]. Cell, 2018, 173(1):248-259.
[45] NIWA H, TOYOOKA Y, SHIMOSATO D, et al.Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation[J]. Cell, 2005, 123(5):917-929.
[46] LIU S, BOU G, SUN R, et al.Sox2 is the faithful marker for pluripotency in pig:Evidence from embryonic studies[J]. Developmental Dynamics, 2015, 244(4):619-627.
[47] BOU G, LIU S, GUO J, et al.Cdx2 represses Oct4 function via inducing its proteasome-dependent degradation in early porcine embryos[J]. Developmantal Biology, 2016, 410(1):36-44.
[48] FOGARTY N M E, MCCARTHY A, SNIJDERS K E, et al.Genome editing reveals a role for OCT4 in human embryogenesis[J]. Nature, 2017, 550(7674):67-73.
[49] KIM S J, KOO O J, PARK H J, et al.Oct4 overexpression facilitates proliferation of porcine fibroblasts and development of cloned embryos[J]. Zygote, 2015, 23(5):704-711.
[50] LE BIN G C, MUNOZ-DESCALZO S, KUROWSKI A, et al.Oct4 is required for lineage priming in the developing inner cell mass of the mouse blastocyst[J]. Development, 2014, 141(5):1001-1010.
[51] SIMMET K, ZAKHARTCHENKO V, PHILIPPOU-MASSIER J, et al.OCT4/POU5F1 is required for NANOG expression in bovine blastocysts[J]. Proceeding of The National Academy of Sciences of The Unted States of America, 2018, 115(11):2770-2775.
[52] GU P, GOODWIN B, CHUNG A C, et al.Orphan nuclear receptor LRH-1 is required to maintain Oct4 expression at the epiblast stage of embryonic development[J]. Molecular and Cellular Biology, 2005, 25(9):3492-3505.
[53] LI Y Q.Networks of transcription factors for Oct4 expression in mice[J]. DNA and Cell Biology, 2017, 36(9):725-736.
[54] SUNG B, DO H J, PARK S W, et al.Regulation of OCT4 gene expression by liver receptor homolog-1 in human embryonic carcinoma cells[J]. Biochemical and Biophys Research Communication, 2012, 427(2):315-320.
[55] WEIKUM E R, TUNTLAND M L, MURPHY M N, et al.A structural investigation into Oct4 regulation by orphan nuclear receptors, germ cell nuclear factor (GCNF), and liver receptor homolog-1(LRH-1)[J]. Journal of Molecular Biology, 2016, 428(24 Pt B):4981-4992.
[56] GUO J, ZHAO M H, LIANG S, et al.Liver receptor homolog 1 influences blastocyst hatching in pigs[J]. Journal of Reproduction and Development, 2016, 62(3):297-303.
[57] VIZLIN-HODZIC D, JOHANSSON H, RYME J, et al.SAF-A has a role in transcriptional regulation of Oct4 in ES cells through promoter binding[J]. Cell Reprogram, 2011, 13(1):13-27.
[58] CHUANG Y S, HUANG W H, PARK S W, et al.Promyelocytic leukemia protein in retinoic acid-induced chromatin remodeling of Oct4 gene promoter[J]. Stem Cells, 2011, 29(4):660-669.
[59] WANG K, SENGUPTA S, MAGNANI L, et al.Brg1 is required for Cdx2-mediated repression of Oct4 expression in mouse blastocysts[J]. PLoS One, 2010, 5(5):e10622.
[60] PARISI S, PASSARO F, ALOIA L, et al.Klf5 is involved in self-renewal of mouse embryonic stem cells[J]. Journal of Cell Science, 2008, 121(Pt 16):2629-2634.
[61] WEI Z, YANG Y, ZHANG P, et al.Klf4 interacts directly with Oct4 and Sox2 to promote reprogramming[J]. Stem Cells, 2009, 27(12):2969-2978.
[62] WEI Z, GAO F, KIM S, et al.Klf4 organizes long-range chromosomal interactions with the oct4 locus in reprogramming and pluripotency[J]. Cell Stem Cell, 2013, 13(1):36-47.
[63] FANG L, ZHANG J, ZHANG H, et al.H3K4 methyltransferase Set1a is a key Oct4 coactivator essential for generation of Oct4 positive inner cell mass[J]. Stem Cells, 2016, 34(3):565-580.
[64] ZHANG X, ZHANG J, WANG T, et al.Esrrb activates Oct4 transcription and sustains self-renewal and pluripotency in embryonic stem cells[J]. Journal of Biological Chemistry, 2008, 283(51):35825-35833.
[65] LI J, LI J, CHEN B.Oct4 was a novel target of Wnt signaling pathway[J]. Molecular and Cellular Biochemistry, 2012, 362(1-2):233-240.
[66] CHEN C Y, LEE D S, YAN Y T, et al.Bcl3 bridges LIF-STAT3 to Oct4 signaling in the maintenance of naïve pluripotency[J]. Stem Cells, 2015, 33(12):3468-3480.
[67] LI H, FAN R, SUN M, et al.Nspc1 regulates the key pluripotent Oct4-Nanog-Sox2 axis in P19 embryonal carcinoma cells via directly activating Oct4[J]. Biochemical and Biophys Research Communication, 2013, 440(4):527-532.
[68] TAMM C, BÖWER N, ANNERÉN C.Regulation of mouse embryonic stem cell self-renewal by a Yes-YAP-TEAD2 signaling pathway downstream of LIF[J]. Journal of Cell Science, 2011, 124(Pt 7):1136-1144.
[69] MASUI S, NAKATAKE Y, TOYOOKA Y, et al.Pluripotency governed by Sox2via regulation of Oct3/4 expression in mouse embryonic stem cells[J]. Nature Cell Biology, 2007, 9(6):625-635.
[70] LI Y Q.Master stem cell transcription factors and signaling regulation[J]. Cell Reprogram, 2010, 12(1):3-13.
[71] OKUMURA-NAKANISHI S, SAITO M, NIWA H, et al.Oct-3/4 and Sox2 regulate Oct-3/4 gene in embryonic stem cells[J]. Journal of Biological Chemistry, 2005, 280(7):5307-5317.
[72] RIZZINO A, WUEBBEN E L.Sox2/Oct4:A delicately balanced partnership in pluripotent stem cells and embryogenesis[J]. Biochimica et Biophysica Acta, 2016, 1859(6):780-791.
[73] DO E K, CHEON H C, JANG I H, et al.Reptin regulates pluripotency of embryonic stem cells and somatic cell reprogramming through Oct4-dependent mechanism[J]. Stem Cells, 2014, 32(12):3126-3136.
[74] CHOI I, CAREY T S, WILSON C A, et al.Evidence that transcription factor AP-2γ is not required for Oct4 repression in mouse blastocysts[J]. PLoS One, 2013, 8(5):e65771.
[75] GALONSKA C, ZILLER M J, KARNIK R, et al.Ground state conditions induce rapid reorganization of core pluripotency factor binding before global epigenetic reprogramming[J]. Cell Stem Cell, 2015, 17(4):462-470.
[76] RAZIN A.CpG methylation, chromatin structure and gene silencing-a three-way connection[J]. The EMBO Journal, 1998, 17(17):4905-4908.
[77] SHARIFI-ZARCHI A, GEROVSKA D, ADACHI K, et al.DNA methylation regulates discrimination of enhancers from promoters through a H3K4me1-H3K4me3 seesaw mechanism[J]. BMC Genomics, 2017, 18(1):964.
[78] HATTORI N, NISHINO K, KO Y G, et al.Epigenetic control of mouse Oct-4 gene expression in embryonic stem cells and trophoblast stem cells[J]. Journal of Biological Chemistry, 2004, 279(17):17063-17069.
[79] OLARIU V, LÖVKVIST C, SNEPPEN K.Nanog, Oct4 and Tet1 interplay in establishing pluripotency[J]. Scientific Reports, 2016, 6:25438.
[80] COSTA Y, DING J, THEUNISSEN T W, et al.NANOG-dependent function of TET1 and TET2 in establishment of pluripotency[J]. Nature, 2013, 495(7441):370-374.
[81] LI J Y, PU M T, HIRASAWA R, et al.Synergistic function of DNA methyltransferases Dnmt3a and Dnmt3b in the methylation of Oct4 and Nanog[J]. Moluecular and Cellular Biology, 2007, 27(24):8748-8759.
[82] SHANAK S, HELMS V.DNA methylation and the core pluripotency network[J]. Developmental Biology, 2020, 464(2):145-160.
[83] CHOI H W, JOO J Y, HONG Y J, et al.Distinct enhancer activity of Oct4 in naive and primed mouse pluripotency[J]. Stem Cell Reports, 2016, 7(5):911-926.
[84] SHAKYA A, CALLISTER C, GOREN A, et al.Pluripotency transcription factor Oct4 mediates stepwise nucleosome demethylation and depletion[J]. Moluecular and Cellular Biology, 2015, 35(6):1014-1025.
[85] CAREY T S, CHOI I, WILSON C A, et al.Transcriptional reprogramming and chromatin remodeling accompanies Oct4 and Nanog silencing in mouse trophoblast lineage[J]. Stem Cells Development, 2014, 23(3):219-229.
[86] WILLIAMS E O, TAYLOR A K, BELL E L, et al.Sirtuin 1 promotes deacetylation of Oct4 and maintenance of naive pluripotency[J]. Cell Reports, 2016, 17(3):809-820.
[87] ETCHEGARAY J P, CHAVEZ L, HUANG Y, et al.The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine[J]. Nature Cell Biology, 2015, 17(5):545-557.
[88] ZHANG C, HUANG S, ZHUANG H, et al.YTHDF2 promotes the liver cancer stem cell phenotype and cancer metastasis by regulating OCT4 expression via m6A RNA methylation[J]. Oncogene, 2020, 39(23):4507-4518.