Research into regulation of the differentiation of stem cells is critical to understanding early developmental decisions and later development growth. The transcription factor ARID3A previously was shown to be critical for trophectoderm and hematopoetic development. Expression of ARID3A increases during embryonic differentiation, but the underlying reason remained unclear. Here we show that Arid3a null embryonic stem (ES) cells maintain an undifferentiated gene expression pattern and form teratomas in immune-compromised mice. However, Arid3a null ES cells differentiated in vitro into embryoid bodies (EBs) significantly faster than control ES cells, and the majority forming large cystic embryoid EBs. Analysis of gene expression during this transition indicated that Arid3a nulls differentiated spontaneously into mesoderm and neuroectoderm lineages. While young ARID3A-deficient mice showed no gross tissue morphology, proliferative and structural abnormalities were observed in the kidneys of older null mice. Together these data suggest that ARID3A is not only required hematopoiesis, but is critical for early mesoderm differentiation.
Martello G, Smith A. The nature of embryonic stem cells. Annu Rev Cell Dev Biol. 2014; 30; 647-675. Ref.: https://goo.gl/2fQ2im
Hemberger M, Dean W, Reik W. Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington’s canal. Nat Rev Mol Cell Biol. 2009; 10; 526-537. Ref.: https://goo.gl/zmVgwx
Nixon JC, Ferrell S, Miner C, Oldham AL, Hochgeschwender U, et al. Transgenic mice expressing dominant-negative Arid3a exhibit defects in B1 B cells. J Immunol Baltim Md. 2008; 181; 6913-6922. Ref.: https://goo.gl/suWSPu
Webb CF, Bryant J, Popowski M, Allred L, Kim D, et al. The ARID family transcription factor Arid3a is required for both hematopoietic stem cell and B lineage development. Mol Cell Biol. 2011; 31; 1041-1053. Ref.: https://goo.gl/wGgErP
Kim PG, Canver MC, Rhee C, Ross SJ, Harriss JV, et al. Interferon-α signaling promotes embryonic HSC maturation. Blood. 2016; 128: 204-216. Ref.: https://goo.gl/nTGHsW
Rhee C, Edwards M, Dang C, Harris J, Brown M, et al. ARID3A is required for mammalian placenta development. Dev Biol. 2017; 422: 83-91. Ref.: https://goo.gl/Dq2rku
Rhee C, Lee BK, Beck S, Anjum A, Cook KR, Popowski M, et al. Corrigendum: Arid3a is essential to execution of the first cell fate decision via direct embryonic and extraembryonic transcriptional regulation. Genes Dev. 2015; 29: 1890. Ref.: https://goo.gl/aSTe3c
An G, Miner CA, Nixon JC, Kincade PW, Bryant J, et al. Loss of Arid3a/ARID3a function promotes developmental plasticity. Stem Cells Dayt Ohio. 2010; 28: 1560-1567. Ref.: https://goo.gl/NFFfUf
Popowski M, Templeton TD, Lee BK, Rhee C, Li H, et al. Arid3a/Arid3A Acts as a Barrier to Somatic Cell Reprogramming through Direct Regulation of Oct4, Sox2, and Nanog. Stem Cell Rep. 2014; 2: 26-35. Ref.: https://goo.gl/ZUgmtk
Wang J, Rao S, Chu J, Shen X, Levasseur DN, et al. A protein interaction network for pluripotency of embryonic stem cells. Nature. 2006; 444: 364-368. Ref.: https://goo.gl/aWnkHB
Itskovitz-Eldor J, Schuldiner M, Karsenti D, Eden A, Yanuka O, et al. Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Mol Med. 2000; 6: 88-95. Ref.: https://goo.gl/Vrwepk
Kurosawa H. Methods for Inducing Embryoid Body Formation: In Vitro Differentiation System of Embryonic Stem Cells. J Biosci Bioeng. 2007; 103: 389-398. Ref.: https://goo.gl/YhYLHo
Wang R, Clark R, Bautch VL. Embryonic stem cell-derived cystic embryoid bodies form vascular channels: an in vitro model of blood vessel development. Dev Camb Engl. 1992; 114: 303-316. Ref.: https://goo.gl/daxwVF
Doetschman TC, Eistetter H, Katz M, Schmidt W, Kemler R. The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J Embryol Exp Morphol. 1985; 87: 27-45. Ref.: https://goo.gl/WKVyCQ
Yasuda E, Seki Y, Higuchi T, Nakashima F, Noda T, et al. Development of cystic embryoid bodies with visceral yolk-sac-like structures from mouse embryonic stem cells using low-adherence 96-well plate. J Biosci Bioeng. 2009; 107: 442-446. Ref.: https://goo.gl/a4Pi8d
Ng YS, Ramsauer M, Loureiro RMB, D’Amore PA. Identification of genes involved in VEGF-mediated vascular morphogenesis using embryonic stem cell-derived cystic embryoid bodies. Lab Invest. 2004; 84: 1209-1218. Ref.: https://goo.gl/6QALJf
Fuegemann CJ, Samraj AK, Walsh S, Fleischmann BK, Jovinge S, et al. Differentiation of Mouse Embryonic Stem Cells into Cardiomyocytes via the Hanging-Drop and Mass Culture Methods. Curr Protoc Stem Cell Biol. Ref.: https://goo.gl/fKxcSo
Kim D, Tucker PW. A regulated nucleocytoplasmic shuttle contributes to Arid3a’s function as a transcriptional activator of immunoglobulin genes. Mol Cell Biol. 2006; 26: 2187-2201. Ref.: https://goo.gl/JGdVXL
Schmidt C, Kim D, Ippolito GC, Naqvi HR, Probst L, et al. Signalling of the BCR is regulated by a lipid rafts-localised transcription factor, Bright. EMBO J. 2009; 28: 711-724. Ref.: https://goo.gl/9ehCcC
Ma K, Araki K, Ichwan SJ, Suganuma T, Tamamori-Adachi M, et al. E2FBP1/DRIL1, an AT-rich interaction domain-family transcription factor, is regulated by p53. Mol. Cancer Res. 2003; 1: 438-444. : https://goo.gl/c9pZrR
Peeper DS, Shvarts A, Brummelkamp T, Douma S, Koh EY, et al. A functional screen identifies hDRIL1 as an oncogene that rescues RAS-induced senescence. Nat Cell Biol. 2002; 4:148-153. Ref.: https://goo.gl/8fQDEL
Lin L, Zhou Z, Zheng L, Alber S, Watkins S, et al. Cross talk between Id1 and its interactive protein Dril1 mediate fibroblast responses to transforming growth factor-beta in pulmonary fibrosis. Am J Pathol. 2008; 173: 337-346. Ref.: https://goo.gl/uCbTzr
Zong RT, Tucker PW, Das C. Regulation of matrix attachment region-dependent, lymphocyte-restricted transcription through differential localization within promyelocytic leukemia nuclear bodies. EMBO J. 2000; 19: 4123-4133. Ref.: https://goo.gl/W31L98
Lin D, Ippolito GC, Zong RT, Bryant J, Koslovsky J, et al. Arid3a/ARID3A contributes to chromatin accessibility of the immunoglobulin heavy chain enhancer. Mol Cancer. 2007; 6: 23. Ref.: https://goo.gl/jAvdqX
Webb CF, Ratliff ML, Powell R, Wirsig-Wiechmann CR, Lakiza O, et al. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures. Biochem Biophys Res Commun. 2015; 463: 1334-1340. Ref.: https://goo.gl/o3Qa7N
Bosnali M, Münst B, Thier M, Edenhofer F. Deciphering the stem cell machinery as a basis for understanding the molecular mechanism underlying reprogramming. Cell Mol Life Sci. 2009; 66: 3403-3420. Ref.: https://goo.gl/FTXrNa
Chambers I. The Molecular Basis of Pluripotency in Mouse Embryonic Stem Cells. Cloning Stem Cells. 2004; 6, 386-391. Ref.: https://goo.gl/6YBo8d
Kopp JL, Ormsbee BD, Desler M, Rizzino A. Small Increases in the Level of Sox2 Trigger the Differentiation of Mouse Embryonic Stem Cells. STEM CELLS. 2008; 26: 903-911. Ref.: https://goo.gl/zKL2TW
Rhee C, Lee BK, Beck S, Anjum A, Cook KR, et al. Arid3a is essential to execution of the first cell fate decision via direct embryonic and extraembryonic transcriptional regulation. Genes Dev. 2014; 28: 2219-2232. Ref.: https://goo.gl/GV6Bb3
Nagy A. Manipulating the Mouse Embryo: A Laboratory Manual, Third Edition. 2002. Ref.: https://goo.gl/vpdDo1
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