Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ex Vivo Expansion Potential of Murine Hematopoietic Stem Cells: A Rare Property Only Partially Predicted by Phenotype

ABSTRACT: The scarcity of hematopoietic stem cells (HSCs) restricts their use in both clinical settings and experimental research. Here, we examined a recently developed method for expanding rigorously purified murine HSCs ex vivo. Input HSCs displayed varying potential for ex vivo self-renewal, with alternative outcomes revealed by single cell multimodal RNA- and ATAC-seq profiling. While most HSC progeny offered only transient in vivo reconstitution, these cells efficiently rescued mice from lethal myeloablation. The amplification of functional HSC activity allowed for long-term multilineage engraftment in unconditioned hosts that somewhat surprisingly associated with a return of HSCs to quiescence. Thereby, our findings identify several key considerations for ex vivo HSC expansion, with major implications also for assessment of normal HSC activity.

ORGANISM(S): Mus musculus

PROVIDER: GSE234906 | GEO | 2023/11/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Molecular characterization of hematopoietic stem cells after in vitro amplification on biomimetic 3D PDMS cell culture scaffoldsMolecular characterization of hematopoietic stem cells after in vitro amplification on biomimetic 3D PDMS cell culture scaffolds

Project description:Hematopoietic stem cell transplantation (HSCT) is successfully applied since the late 1950s, however, its efficacy still needs to be improved. A promising strategy is to transplant high numbers of pluripotent hematopoietic stem cells (HSCs). Therefore, an advanced ex vivo culture system is needed that supports the proliferation and maintains the pluripotency of HSC to override possible limitations in cell numbers gained from donors. To model the natural HSC niche in vitro and thus, to amplify high numbers of undifferentiated HSCs, we used an optimized HSC cell culture medium in combination with artificial 3D bone marrow-like scaffolds made of polydimethylsiloxane (PDMS). After 14 days in vitro (DIV) cell culture, we performed transcriptome and proteome analysis of the whole cell populations. Ingenuity pathway analysis (IPA) indicated that our 3D PDMS cell culture scaffolds activated interleukin, SREBP, mTOR and FOXO signaling pathways as well as the HSC metabolism, which we confirmed by ELISA, Western blot and metabolic flux analysis. These molecular signaling pathways and HSC metabolism are well known to promote the expansion HSCs and are involved in their pluripotency maintenance. After selection and enrichment of immature CD34-positive/CD38-negative HSCs using FACS sorting, we could confirm our findings by another proteome analysis followed by IPA. Thus, we could show that our 3D bone marrow-like PDMS scaffolds activate key molecular signaling pathways to amplify the numbers of undifferentiated HSC efficiently ex vivo.

2021-11-10 | PXD025849 | Pride

Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells

Project description:Although practiced clinically for more than 40 years, the use of hematopoietic stem cell (HSC) transplants remains limited by the ability to expand these cells ex vivo. An unbiased screen with primary human HSCs identified a purine derivative, StemRegenin 1 (SR1), that promotes the ex vivo expansion of CD34+ cells. Culture of HSCs with SR1 led to a 50-fold increase in cells expressing CD34 and a 17-fold increase in cells that retain the ability to engraft immunodeficient mice. Mechanistic studies show that SR1 acts by antagonizing the aryl hydrocarbon receptor (AHR). The identification of SR1 and AHR modulation as a means to induce ex vivo HSC expansion should facilitate the clinical use of HSC therapy. LGC006, a less potent SR1 analog, was also examined. KEYWORDS: two compounds, multiple doses, one time point two compounds, multiple doses, one time point

2011-04-04 | E-GEOD-28359 | biostudies-arrayexpress

Maturation of hematopoietic stem cells from pre-hematopoietic stem cells is accompanied by upregulation of programmed death ligand 1

Project description:Hematopoietic stem cells (HSCs) in the fetal liver mature from pre-HSCs that originate in the major arteries of the embryo. To generate HSCs from other cell sources it will be necessary to reproduce the maturation of HSCs from pre-HSCs ex vivo. We refined the markers used to purify pre-HSCs and HSCs matured ex vivo, and compared the transcriptomes of pre-HSCs, ex vivo matured HSCs, and fetal liver HSCs. We found that maturation of pre-HSCs into HSCs in vivo or ex vivo is accompanied by the downregulation of genes involved in embryonic development and vasculogenesis, and upregulation of genes involved in hematopoietic organ development, lymphoid development, and immune responses. Ex vivo matured HSCs more closely resemble fetal liver HSCs than pre-HSCs, but are not their molecular equivalents. We show that functional ex vivo-matured and fetal liver HSCs increase the expression of programmed death ligand 1 (PD-L1). PD-L1 does not mark all pre-HSCs, but cell surface PD-L1 was present on functional HSCs after ex vivo culture. PD-L1 signaling, however, is not required for engraftment of embryonic HSCs. Hence, up-regulation of PD-L1 is a correlate of, but not a requirement for HSC maturation.

2017-12-26 | GSE104689 | GEO

Polyvinyl alcohol expanded mouse HSC cultures (bulk RNA-Seq)

Project description:We previously reported a polyvinyl alcohol-based mouse hematopoietic stem cell (HSC) culture protocol that efficiently expanded transplantable HSCs for at least a month ex vivo (Wilkinson et al., Nature 2019). Here, we investigated the molecular consequences of oxygen concentration on 28-day ex vivo HSC cultures using bulk RNA-seq

2023-02-07 | GSE207740 | GEO

STAT1 is essential for hematopoietic stem cell function and maintains a MHC IIhi stem cell subset that resists myeloablation and neoplastic expansion

Project description:Adult hematopoietic stem cells (HSCs) are predominantly quiescent and can be activated in response to acute stress such as infection or cytotoxic insults. STAT1 is a pivotal mediator of interferon (IFN) signaling and is required for IFN-induced HSC proliferation, but the downstream mechanisms remain unclear and in particular little is known about the role of STAT1 in regulating hematopoietic stem/progenitor cells during homeostasis. Here we show that loss of STAT1 alters the steady state hematopoietic stem and progenitor (HSPC) landscape, impairs HSC function in transplantation assays and delays blood cell regeneration following myeloablation. Under steady state conditions STAT1 was essential for several HSC transcriptional programs including expression of genes involved in virus life cycle, a subset of interferon-stimulated genes, MHC class I genes and genes involved in cell cycle arrest. In addition Stat-1 deficient mice lacked a previously unrecognized quiescent subset of homeostatic HSCs with high levels of MHC II expression (MHC IIhi HSCs). This subset was refractory to 5’-FU induced myeloablation and displayed reduced megakaryocytic potential. Mutant calreticulin, which causes increased megakaryopoiesis in human myeloproliferative neoplasms, gave rise to preferential expansion of MHC IIlo HSCs. These data reveal a STAT1 dependent MHC IIhi quiescent HSC subset and show that STAT1 protects HSCs from proliferative exhaustion.

2022-07-05 | GSE180904 | GEO

STAT1 is essential for hematopoietic stem cell function and maintains a MHC IIhi stem cell subset that resists myeloablation and neoplastic expansion [LK]

2022-07-05 | GSE180905 | GEO

Polyvinyl alcohol expanded mouse HSC cultures (scRNA-Seq)

2023-02-07 | GSE207742 | GEO

Distinct Stromal Cell Factor Combinations Can Separately Control Hematopoietic Stem Cell Survival, Proliferation and Self-Renewal

Project description:Hematopoietic stem cells (HSCs) are identified by their ability to sustain prolonged blood cell production in vivo, although recent evidence suggests that durable self-renewal (DSR) is shared by HSC subtypes with distinct self-perpetuating differentiation programs. Net expansions of DSR-HSCs occur in vivo, but molecularly defined conditions that support similar responses in vitro are lacking. We hypothesized that this might require a combination of factors that differentially promote HSC viability, proliferation and self-renewal. We now demonstrate that HSC survival and maintenance of DSR potential is variably supported by different Steel factor (SF)-containing cocktails with similar HSC-mitogenic activities. In addition, stromal cells produce other factors, including nerve growth factor and collagen 1, that can antagonize the apoptosis of initially quiescent adult HSCs and, in combination with SF and interleukin-11, produce >15-fold net expansions of DSR-HSCs ex vivo within 7 days. These findings suggest a new molecular basis for HSC control and expansion. Adult mouse bone marrow CD45+EPCR+CD48-CD150+ cells were used in a total of 4 conditions (fresh, 6 hour stimulation with SF+IL-11+UG26 CM, UG26 CM only, SF+IL-11) with 2 technical replicates per condition.

2014-05-01 | E-GEOD-57220 | biostudies-arrayexpress

Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells

2011-04-04 | GSE28359 | GEO

Hsf1 promotes hematopoietic stem cell fitness and proteostasis in response to ex vivo culture stress and aging II

Project description:Maintaining proteostasis is key to resisting stress and to promoting healthy aging. Proteostasis is necessary to preserve stem cell function, but little is known about the mechanisms that regulate proteostasis during stress in stem cells, and whether disruptions in proteostasis contribute stem cell aging is largely unexplored. We determined that ex vivo cultured mouse and human hematopoietic stem cells (HSCs) rapidly increase protein synthesis. This challenge to HSC proteostasis was associated with nuclear accumulation of Hsf1, and deletion of Hsf1 impaired HSC maintenance ex vivo. Strikingly, supplementing cultures with small molecules that enhance Hsf1 activation partially suppressed protein synthesis, rebalanced proteostasis, and supported retention of HSC serial reconstituting activity. Although Hsf1 was dispensable for young adult HSCs in vivo, Hsf1 deficiency increased protein synthesis and impaired the reconstituting activity of middle-aged HSCs. Hsf1 thus promotes proteostasis and the regenerative activity of HSCs in response to culture stress and aging.

2021-07-11 | GSE179413 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data