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ATAC-seq of uncultured CD112high and CD112low long-term(LT) human hematopoietic stem cells (HSC) from umbilical cord blood

ABSTRACT: We performed ATAC-sequencing to elucidate the chromatin accessibility that underlie the differential in vitro priming and regeneration phenotypes of CD112high and CD112low LT-HSC. Therefore, we prospectively isolated these subpopulations from 3 independent human umbilical cord blood pools and subjected to ATAC-sequencing directly. We show that distinct subsets of human LT-HSC respond differently to regeneration-mediated stress and that INKA1 governs these distinct stemness states where CD112low LT-HSC are marked by an alternative state of quiescence with high INKA1 and low H4K16ac preserving self-renewal and regenerative capacity upon successive rounds of regeneration-mediated stress.

ORGANISM(S): Homo sapiens

PROVIDER: GSE172005 | GEO | 2021/04/13

REPOSITORIES: GEO

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RNA-seq of uncultured CD112high and CD112low and cultured long-term (LT) and short-term (ST) human hematopoietic stem cells (HSC) overexpressing INKA-1

Project description:RNA-seq of uncultured CD112high and CD112low long-term(LT) human hematopoietic stem cells (HSC) and cultured and lentiviral transduced (CTRL, INKA1-OE) LT- and short-term HSC from umbilical cord blood We performed RNA-sequencing to elucidate the biological pathways (1) altered by INKA1 overexpression in LT-HSC and ST-HSC that may contribute to the induced transient restraint in generating proliferative hematopoietic output in vivo and in vitro; and (2) that underlie the differential in vitro priming and regeneration phenotypes of CD112high and CD112low LT-HSC. Therefore, we prospectively isolated indicated subpopulations from 3 independent human umbilical cord blood pools and subjected them either to RNA-sequencing directly or following culture, lentiviral transduction and purification of the transduced cell fractions. We show that distinct subsets of human LT-HSC respond differently to regeneration-mediated stress and that INKA1 governs these distinct stemness states where CD112low LT-HSC are marked by an alternative state of quiescence with high INKA1 preserving self-renewal and regenerative capacity upon successive rounds of regeneration-mediated stress.

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