Unequal segregation of parental chromosomes in embryonic stem cell hybrids

Unequal segregation of parental chromosomes in embryonic stem cell hybrids
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DOI:
10.1002/mrd.20266
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发表时间:
2005-07-01
影响因子:
2.5
通讯作者:
Serov, OL
Serov, OL
中科院分区:
生物学3区
文献类型:
--
作者:
Matveeva, NM;Pristyazhnyuk, IE;Serov, OL

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本文研究了14个种内和20个种间杂交克隆的染色体分离。这些杂交克隆是由小家鼠胚胎干细胞与DD/c小鼠或小家鼠的成纤维细胞或脾细胞融合而成的。作为四倍体核型体外进化的对照,我们使用通过ES细胞(D3)与ES细胞(TgTP 6.3)融合获得的一组杂交克隆。通过微卫星分析和标记的物种特异性探针原位杂交鉴定克隆中的亲本染色体。这两种分析都揭示了三种类型的克隆:(i)稳定的四倍体,只观察到ES × ES细胞杂种;(ii)ES和体细胞伴侣的染色体双侧丢失;(iii)体细胞伴侣的染色体单侧分离。观察到的单边分离是广泛的ES-脾细胞杂交,但较低的ES-成纤维细胞杂交克隆。体细胞伴侣的发育状态可能是染色体定向丢失的原因。非随机分离意味着在亲本同源染色体的初始差异没有立即均衡,这意味着至少短暂的持久性的分化表观基因型。(c)2005 Wiley-Liss,Inc.
Chromosome segregation was studied in 14 intra- and 20 inter-specific hybrid clones generated by fusion of Mus musculus embryonic stem (ES) cells with fibroblasts or splenocytes of DD/c mice or Mus caroli. As a control for in vitro evolution of tetraploid karyotype we used a set of hybrid clones obtained by fusion of ES cells (D3) with ES cells (TgTP6.3). Identification of the parental chromosomes in the clones was performed by microsatellite analysis and in situ hybridization with labeled species-specific probes. Both analyses have revealed three types of clones: (i) stable tetraploid, observed only for ES x ES cell hybrids; (ii) bilateral loss of chromosomes of both ES and somatic partners; (iii) unilateral segregation of chromosomes of the somatic partner. Observed unilateral segregation was extensive in ES-splenocyte cell hybrids, but lower in ES-fibroblast hybrid clones. Developmental state of the somatic partner is presumably responsible for directional chromosome loss. Nonrandom segregation implies that initial differences in the parental homologous chromosomes were not immediately equalized implying at least transient persistence of the differentiated epigenotype. (c) 2005 Wiley-Liss, Inc.