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Hematopoietic stem cells (HSCs)

ABSTRACT: G0 marker-separation of dormant and active hematopoietic stem cells reveals dormancy regulation by basal cytoplasmic calcium

OTHER RELATED OMICS DATASETS IN: GSE139013GSE138884

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Toshio Kitamura

PROVIDER: PXD012093 | JPOST Repository | Thu Dec 19 00:00:00 GMT 2019

REPOSITORIES: jPOST

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			Action	DRS
	171126harry_p27Neg_1.raw	Raw
	171126harry_p27Neg_2.raw	Raw
	171126harry_p27high_1.raw	Raw
	171126harry_p27high_2.raw	Raw
	171126harry_p27low_1.raw	Raw

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Publications

Discrimination of Dormant and Active Hematopoietic Stem Cells by G0 Marker Reveals Dormancy Regulation by Cytoplasmic Calcium.

Fukushima Tsuyoshi T Tanaka Yosuke Y Hamey Fiona K FK Chang Chih-Hsiang CH Oki Toshihiko T Asada Shuhei S Hayashi Yasutaka Y Fujino Takeshi T Yonezawa Taishi T Takeda Reina R Kawabata Kimihito Cojin KC Fukuyama Tomofusa T Umemoto Terumasa T Takubo Keiyo K Takizawa Hitoshi H Goyama Susumu S Ishihama Yasushi Y Honda Hiroaki H Göttgens Berthold B Kitamura Toshio T

Cell reports 20191201 12

Quiescent hematopoietic stem cells (HSCs) are typically dormant, and only a few quiescent HSCs are active. The relationship between "dormant" and "active" HSCs remains unresolved. Here we generate a G0 marker (G0M) mouse line that visualizes quiescent cells and identify a small population of active HSCs (G0Mlow), which are distinct from dormant HSCs (G0Mhigh), within the conventional quiescent HSC fraction. Single-cell RNA-seq ana ...[more]

PMID: 31851939

Similar Datasets

Discrimination of dormant and active hematopoietic stem cells by G0 markers reveals dormancy regulation by cytoplasmic calcium

Project description:Discrimination of dormant and active hematopoietic stem cells by G0 markers reveals dormancy regulation by cytoplasmic calcium

| PRJNA578092 | ENA

Discrimination of dormant and active hematopoietic stem cells by G0 markers reveals dormancy regulation by cytoplasmic calcium

Project description:Discrimination of dormant and active hematopoietic stem cells by G0 markers reveals dormancy regulation by cytoplasmic calcium

| PRJNA577683 | ENA

Discrimination of dormant and active hematopoietic stem cells by G0 markers reveals dormancy regulation by cytoplasmic calcium

Project description:Quiescent hematopoietic stem cells (HSCs) are typically dormant, and only a few quiescent HSCs are active. The relationship between “dormant” and “active” HSCs remains unresolved. Here we generated a G0 marker (G0M) mouse line that visualizes quiescent cells. G0M identifies a small population of active HSCs (G0Mlow), which are distinct from dormant HSCs (G0Mhigh), within the conventional quiescent HSC fraction. Single-cell RNA-Seq analyses showed that the gene expression profiles of these populations were nearly identical, yet differed in their Cdk4/6 activity. Furthermore high-throughput small molecule screening revealed that high concentrations of cytoplasmic calcium ([Ca2+]c) were linked to dormancy of HSCs. These findings indicate that G0M separates dormant and active adult HSCs, which are regulated by Cdk4/6 and [Ca2+]c. This G0M mouse line represents a useful resource for investigating physiologically important stem cell subpopulations.

2019-12-20 | GSE139013 | GEO

Discrimination of dormant and active hematopoietic stem cells by G0 markers reveals dormancy regulation by cytoplasmic calcium

Project description:High-throughput small molecule screening revealed that high concentrations of cytoplasmic calcium ([Ca2+]c) were linked to dormancy of HSCs.To clarify molecular difference between [Ca2+]chigh and [Ca2+]clow cells, we performed RNA-Seq analysis using [Ca2+]chigh and [Ca2+]clow cells.

2019-12-20 | GSE138884 | GEO

CD38 enzymatic activity promotes hematopoietic stem cell dormancy [scRNA-Seq]

Project description:Quiescence is a fundamental property that protects hematopoietic stem cells’ (HSCs) function throughout life. A subpopulation of deeply quiescent, so-called dormant HSCs (dHSCs) harbors the highest long-term blood repopulation capacity and resides at the top of the hematopoietic hierarchy. However, the mechanisms of HSC dormancy remain elusive, mainly due to the absence of surface markers for dHSCs’ prompt isolation. We identified CD38 nicotinamide adenine dinucleotide (NAD+) catabolic ecto-enzyme as a novel surface marker for murine dHSCs. The product of CD38 cyclase activity – cyclic adenosine diphosphate ribose (cADPR), regulates the expression of the transcription factor and cell cycle regulator c-Fos via an increase of cytoplasmic Ca2+ concentration. Strikingly, we uncovered that c-Fos drives HSCs quiescence through the induction of the cell cycle inhibitor p57Kip2 expression. Moreover, we found a similar CD38-dependent mechanism of quiescence regulation for human HSCs, which are CD38 negative. Specifically, we found that CD38 ecto-enzymatic activity at the neighboring CD38-positive cells promote human HSCs’ dormancy. Together, our work reveals how extracellular metabolic cues trigger a signaling cascade blocking HSC cell cycle entrance. Pharmacological manipulations of defined pathway will provide new strategies to modulate HSCs activation upon infections, blood loss or transplantation in clinical practice.

2022-02-18 | GSE196759 | GEO

CD38 enzymatic activity promotes hematopoietic stem cell dormancy [bulk RNA-Seq]

2022-02-18 | GSE196758 | GEO

Akt signalling leads to stem cell activation and promotes tumour development in epidermis.

Project description:A permantly active form of the oncogene Akt was expressed in the keratinocytes of the basal proliferative layer of the epidermis. Stem cells of the hair follicle expressing the cell surface marker CD34 were isolated. RNA form the CD34(+) and CD34(-) keratinocytes was extracted and and hybridized to Mouse Genome 430 2.0 Affymetrix arrays. Gene expression was compared between CD34(+) hair follicle stem cells and CD34(-) cells isolates from the back skin of K5-myrAkt transgenic mice.

2014-01-26 | E-GEOD-48522 | biostudies-arrayexpress

Akt signalling leads to stem cell activation and promotes tumour development in epidermis.

2014-01-26 | GSE48522 | GEO

Gene expression profiles of Notch signaling suppression in prostate basal cells.

2012-11-08 | GSE34067 | GEO

Gene expression profiles of Notch signaling suppression in prostate basal cells.

Project description:The role of Notch signaling in the maintenance and differentiation of adult prostate stem cells remains unclear. We found that Notch ligands are mainly expressed within the basal cell lineage, while active Notch signaling is detected in both the prostate basal and luminal cell lineages. Disrupting the canonical Notch effector RBP-J impairs the differentiation of prostate basal stem cells and increases their proliferation in vitro and in vivo, but does not affect luminal cell biology. Conversely, ectopic Notch activation in adult prostates results in basal cell depletion and luminal cell hyper-proliferation. TGFÎ² dominates over Notch and overrides Notch ablation-induced proliferation of prostate basal cells. In turn, Notch confers positive feedback by up-regulating a plethora of TGFÎ² signaling components including TGFÎ²RI. These findings reveal crucial roles of the self-enforced positive reciprocal regulatory loop between TGFÎ² and Notch in maintaining prostate basal stem cell dormancy. We employed an in vitro prostate sphere assay to further investigate how Notch signaling regulates basal cell proliferation and differentiation. FACS isolated adult murine prostate basal cells (using FVB mice) were cultured in the prostate sphere assay with or without N-[(3,5-Difluorophenyl)acetyl]-L-alanyl-2-phenyl]glycine-1,1-dimethylethyl ester (DAPT), an inhibitor for the Î³-Secretase complex. Gene expression profiles were taken of vehicle- and DAPT-treated prostate spheres.

2012-11-08 | E-GEOD-34067 | biostudies-arrayexpress