TY - JOUR
T1 - In Vivo Clonal Analysis Reveals Random Monoallelic Expression in Lymphocytes That Traces Back to Hematopoietic Stem Cells
AU - Kubasova, Nadiya
AU - Alves-Pereira, Clara F.
AU - Gupta, Saumya
AU - Vinogradova, Svetlana
AU - Gimelbrant, Alexander
AU - Barreto, Vasco M.
N1 - Publisher Copyright:
Copyright © 2022 Kubasova, Alves-Pereira, Gupta, Vinogradova, Gimelbrant and Barreto.
PY - 2022/8/8
Y1 - 2022/8/8
N2 - 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 in vivo, 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 in vitro (up to 15%) 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.
AB - 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 in vivo, 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 in vitro (up to 15%) 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.
KW - RNA-seq
KW - X-chromosome inactivation (XCI)
KW - allele-specific expression
KW - allelic imbalance (AI)
KW - clonal analysis
KW - epigenetics
KW - hematopoietic stem cell (HSC)
KW - random monoallelic expression (RME)
UR - http://www.scopus.com/inward/record.url?scp=85136528059&partnerID=8YFLogxK
U2 - 10.3389/fcell.2022.827774
DO - 10.3389/fcell.2022.827774
M3 - Article
AN - SCOPUS:85136528059
SN - 2296-634X
VL - 10
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 827774
ER -