AUTHOR=Kubasova Nadiya , Alves-Pereira Clara F. , Gupta Saumya , Vinogradova Svetlana , Gimelbrant Alexander , Barreto Vasco M. 

TITLE=In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.827774

DOI=10.3389/fcell.2022.827774

ISSN=2296-634X

ABSTRACT=Evaluating the epigenetic landscape in the stem cell compartment at the single-cell level is essential to assess their heterogeneity and predict their fate. Here we evaluated the allelic expression imbalance, as a read-out of epigenetic marking, in the progeny of single hematopoietic stem cells (HSC) in vivo, by a genome-wide transcriptomics approach. After four 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 HSC 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 high frequency of genes (up to 15%) under RME in clones expanded in vitro, previously reported, is not found in clones undergoing multiple differentiation steps in vivo; 3) prior to differentiation, HSCs have stable patterns of autosomal RME. We propose that most RME patterns in autosomal chromosomes are erased and established de novo during cell lineage differentiation.