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Single cell hibernation cultures identify molecules dispensable for haematopoietic stem cell self-renewal

ABSTRACT: Single cell hibernation cultures identify molecules dispensable for haematopoietic stem cell self-renewal

PROVIDER: PRJNA672062 | ENA |

REPOSITORIES: ENA

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Single cell hibernation cultures identify molecules dispensable for haematopoietic stem cell self-renewal

Project description:Advances in the isolation and gene expression profiling of single haematopoietic stem cells (HSCs) have permitted in-depth resolution of their molecular program. However, long-term HSCs (LT-HSCs) can only be isolated to near purity from adult mouse bone marrow, thereby precluding studies of their molecular program in different physiological states. Here, we describe a powerful 7-day culture system that removes single LT-HSCs from their native bone marrow microenvironment without compromising their functional potential. LT-HSCs are maintained as single cells and retain full HSC function compared to freshly isolated LT-HSCs with respect to divisional kinetics, colony forming cell potential (73.9%), and transplantation into primary (53%) and secondary (44%) recipients. Comparison of molecular profiles of single hibernating LT-HSCs to freshly isolated counterparts showed a high degree of similarity, but also identified key factors dispensable for LT-HSC function in transplantation assays including members of the AP1 complex (Jun, Fos, and Ncor2), Sult1a1 and Cish.

2021-04-06 | GSE160131 | GEO

MLLT3 governs human haematopoietic stem-cell self-renewal and engraftment.

Project description: Not available

| S-EPMC7278275 | biostudies-literature

Haemopedia: Mouse Haematopoietic Gene Expression

Project description:Database of gene expression in different haematopoietic cell types at haemosphere.org.

2018-11-29 | GSE116177 | GEO

Haemopedia: Human Haematopoietic Gene Expression

Project description:Database of gene expression in different haematopoietic cell types at haemosphere.org

2018-11-29 | GSE115736 | GEO

Landscape of m6A modification in haematopoietic system unveils an essential role of IGF2BP2 in preserving haematopoietic stem cell function

Project description:N6-methyladenosine (m6A) is an abundant modification on mRNA, and plays critical functions in various cellular processes, including cell fate determination and lineage transition. However, the landscape and dynamics of m6A modification in haematopoietic system remain unknown. Here, we delineate a comprehensive m6A landscape across haematopoietic hierarchy and uncover that IGF2BP2 is required for preserving haematopoietic stem cells (HSCs) function. Our data reveal a marked cell-type- and haematopoietic-lineage-specific m6A landscape. Intriguingly, most m6A modifications arise in the early stat of haematopoiesis, and are critical in defining cellular states of HSCs. Moreover, m6A modification is the major factor in determining mRNA abundance in HSCs. Importantly, we find that higher expression of m6A reader IGF2BP2 is critical in controlling gene expression states and the functional maintenance of HSCs. IGF2BP2 deficiency induces apoptosis and quiescence loss, and substantially impairs the reconstitution capacity of HSCs. In addition, deletion of IGF2BP2 increases the mitochondrial activity of HSCs. Mechanistically, IGF2BP2 stabilizes Bmi1 mRNA in an m6A-dependent manner, which represses the expression of mitochondria-related genes. Collectively, our results present a fascinating portrait of m6A modification during haematopoiesis, and uncover a key role of IGF2BP2 in maintaining HSCs function by regulating Bmi1 stability and restraining mitochondrial activity.

2021-10-26 | GSE165863 | GEO

Nociceptive nerves regulate haematopoietic stem cell mobilization

Project description:Nociceptive nerves regulate haematopoietic stem cell mobilization

| PRJNA657999 | ENA

Single-cell RNA sequencing of hPSC-derived endothelial-to-haematopoietic transition

Project description:scRNAseq of sequential time points and CDKi-treated samples during endothelial-to-haematopoietic transition in cells derived by hPSC differentiation.

2020-07-31 | E-MTAB-8205 | biostudies-arrayexpress

Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy.

Project description: Not available

| S-EPMC4015622 | biostudies-literature

Long cell-free DNA molecules in maternal plasma

Project description:We revealed a large population of long cell-free DNA molecules (up to 23,635 bp in length) in maternal plasma and developed an approach which leveraged the abundance of CpG sites on long molecules to deduce the tissue of origin of individual plasma DNA molecules based on single-molecule methylation analysis. We illustrated how such an approach may be utilized to achieve noninvasive prenatal testing of monogenic diseases. We also revealed a reduction in amounts of such long cell-free DNA molecules and a different end motif profile in maternal plasma DNA from pregnancies with preeclampsia.

| EGAS00001005515 | EGA

The histone acetyltransferase KAT6B is required for haematopoietic stem cell development and function

Project description:The histone lysine acetyltransferase KAT6B (MYST4, MORF, QKF) is the target of recurrent chromosomal translocations causing haematological malignancies with poor prognosis. Using Kat6b germline deletion and overexpression in mice, we determined the role of KAT6B in the haematopoietic system. We found that KAT6B sustained the fetal haematopoietic stem cell pool but did not affect viability or differentiation. KAT6B was essential for normal levels of histone H3 lysine 9 (H3K9) acetylation but not for a previously proposed target, H3K23. Compound heterozygosity of Kat6b and the closely related gene, Kat6a, abolished haematopoietic reconstitution after transplantation. KAT6B and KAT6A cooperatively promoted transcription of genes regulating haematopoiesis, including the Hoxa cluster, Pbx1, Meis1, Gata family, Erg and Flt3. In conclusion, we identified the haematopoietic processes requiring Kat6b and showed that KAT6B and KAT6A synergistically promoted HSC development, function and transcription. Our findings are pertinent to current clinical trials testing KAT6A/B inhibitors as cancer therapeutics.

2024-02-25 | GSE256039 | GEO

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