Kubasova Nadiya, Alves-Pereira Clara F, Gupta Saumya, Vinogradova Svetlana, Gimelbrant Alexander, Barreto Vasco M
Chronic Diseases Research Centre, Nova Medical School, CEDOC, Lisbon, Portugal.
Genetagus, Egas Moniz - Cooperativa de Ensino Superior, CRL, Monte de Caparica, Portugal.
Front Cell Dev Biol. 2022 Aug 8;10:827774. doi: 10.3389/fcell.2022.827774. eCollection 2022.
Evaluating the epigenetic landscape in the stem cell compartment at the single-cell level is essential to assess the cells' heterogeneity and predict their fate. Here, using a genome-wide transcriptomics approach , we evaluated the allelic expression imbalance in the progeny of single hematopoietic cells (HSCs) as a read-out of epigenetic marking. After 4 months of extensive proliferation and differentiation, we found that X-chromosome inactivation (XCI) is tightly maintained in all single-HSC derived hematopoietic cells. In contrast, the vast majority of the autosomal genes did not show clonal patterns of random monoallelic expression (RME). However, a persistent allele-specific autosomal transcription in HSCs and their progeny was found in a rare number of cases, none of which has been previously reported. These data show that: 1) XCI and RME in the autosomal chromosomes are driven by different mechanisms; 2) the previously reported high frequency of genes under RME in clones expanded (up to 15%) is not found in clones undergoing multiple differentiation steps ; 3) prior to differentiation, HSCs have stable patterns of autosomal RME. We propose that most RME patterns in autosomal chromosomes are erased and established during cell lineage differentiation.
在单细胞水平评估干细胞区室中的表观遗传格局对于评估细胞的异质性和预测其命运至关重要。在此，我们使用全基因组转录组学方法，评估单个造血细胞（HSC）后代中的等位基因表达失衡，以此作为表观遗传标记的一种读出方式。经过4个月的广泛增殖和分化后，我们发现X染色体失活（XCI）在所有源自单个HSC的造血细胞中都得到严格维持。相比之下，绝大多数常染色体基因并未表现出随机单等位基因表达（RME）的克隆模式。然而，在少数情况下，在HSC及其后代中发现了持续的等位基因特异性常染色体转录，此前均未见相关报道。这些数据表明：1）常染色体中的XCI和RME由不同机制驱动；2）在经历多个分化步骤的克隆中未发现先前报道的在扩增克隆中RME基因的高频率（高达15%）；3）在分化之前，HSC具有稳定的常染色体RME模式。我们提出，常染色体中的大多数RME模式在细胞谱系分化过程中被消除并重新建立。
