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Changing nuclear landscape and unique PML structures during early epigenetic transitions of human embryonic stem cells
Author(s) -
Butler John T.,
Hall Lisa L.,
Smith Kelly P.,
Lawrence Jeanne B.
Publication year - 2009
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22183
Subject(s) - lamin , biology , nuclear lamina , microbiology and biotechnology , epigenomics , embryonic stem cell , somatic cell , induced pluripotent stem cell , mitosis , homeobox protein nanog , stem cell , nuclear pore , death associated protein 6 , genetics , transcription factor , nuclear protein , gene , cytoplasm , dna methylation , gene expression , nucleus
The complex nuclear structure of somatic cells is important to epigenomic regulation, yet little is known about nuclear organization of human embryonic stem cells (hESC). Here we surveyed several nuclear structures in pluripotent and transitioning hESC. Observations of centromeres, telomeres, SC35 speckles, Cajal Bodies, lamin A/C and emerin, nuclear shape and size demonstrate a very different “nuclear landscape” in hESC. This landscape is remodeled during a brief transitional window, concomitant with or just prior to differentiation onset. Notably, hESC initially contain abundant signal for spliceosome assembly factor, SC35, but lack discrete SC35 domains; these form as cells begin to specialize, likely reflecting cell‐type specific genomic organization. Concomitantly, nuclear size increases and shape changes as lamin A/C and emerin incorporate into the lamina. During this brief window, hESC exhibit dramatically different PML‐defined structures, which in somatic cells are linked to gene regulation and cancer. Unlike the numerous, spherical somatic PML bodies, hES cells often display ∼1–3 large PML structures of two morphological types: long linear “rods” or elaborate “rosettes”, which lack substantial SUMO‐1, Daxx, and Sp100. These occur primarily between Day 0–2 of differentiation and become rare thereafter. PML rods may be “taut” between other structures, such as centromeres, but clearly show some relationship with the lamina, where PML often abuts or fills a “gap” in early lamin A/C staining. Findings demonstrate that pluripotent hES cells have a markedly different overall nuclear architecture, remodeling of which is linked to early epigenomic programming and involves formation of unique PML‐defined structures. J. Cell. Biochem. 107: 609–621, 2009. © 2009 Wiley‐Liss, Inc.