Flow cytometry analysis of murine hematopoietic stem cells

Mayle, Allison; Luo, Min; Jeong, Mira; Goodell, Margaret A.

doi:10.1002/cyto.a.22093

Cited by 110 publications

(87 citation statements)

References 42 publications

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“…16 wk, it is possible that UVR affects LTHSCs (11). Although there are variations on how to define LTHSCs phenotypically, these cells are best characterized by their functional ability to provide long-term hematopoietic renewal (.16 wk) (42).…”

Section: Discussionmentioning

confidence: 99%

Altered Immunity and Dendritic Cell Activity in the Periphery of Mice after Long-Term Engraftment with Bone Marrow from Ultraviolet-Irradiated Mice

Scott

Strickland

et al. 2013

The Journal of Immunology

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Alterations to dendritic cell (DC) progenitors in the bone marrow (BM) may contribute to long-lasting systemic immunosuppression (>28 d) following exposure of the skin of mice to erythemal UV radiation (UVR). DCs differentiated in vitro from the BM of mice 3 d after UVR (8 kJ/m2) have a reduced capacity to initiate immunity (both skin and airways) when adoptively transferred into naive mice. Studies in IL-10−/− mice suggested that UV-induced IL-10 was not significantly involved. To investigate the immune capabilities of peripheral tissue DCs generated in vivo from the BM of UV-irradiated mice, chimeric mice were established. Sixteen weeks after reconstitution, contact hypersensitivity responses were significantly reduced in mice reconstituted with BM from UV-irradiated mice (UV-chimeric). When the dorsal skin of UV-chimeric mice was challenged with innate inflammatory agents, the hypertrophy induced in the draining lymph nodes was minimal and significantly less than that measured in control-chimeric mice challenged with the same inflammatory agent. When DCs were differentiated from the BM of UV-chimeric mice using FLT3 ligand or GM-CSF + IL-4, the cells maintained a reduced priming ability. The diminished responses in UV-chimeric mice were not due to different numerical or proportional reconstitution of BM or the hematopoietic cells in blood, lymph nodes, and skin. Erythemal UVR may imprint a long-lasting epigenetic effect on DC progenitors in the BM and alter the function of their terminally differentiated progeny.

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Section: Discussionmentioning

confidence: 99%

Altered Immunity and Dendritic Cell Activity in the Periphery of Mice after Long-Term Engraftment with Bone Marrow from Ultraviolet-Irradiated Mice

Scott

Strickland

et al. 2013

The Journal of Immunology

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“…BM cell isolation, LSK cell sorting, and flow cytometric analysis of cell surface markers were performed as previously described (43,69). Briefly, BM cells were flushed from the long bones (tibias and femurs) of mice with Iscove's modified Dulbecco's…”

Section: Methodsmentioning

confidence: 99%

NRF2-mediated Notch pathway activation enhances hematopoietic reconstitution following myelosuppressive radiation

et al. 2014

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A nuclear disaster may result in exposure to potentially lethal doses of ionizing radiation (IR). Hematopoietic acute radiation syndrome (H-ARS) is characterized by severe myelosuppression, which increases the risk of infection, bleeding, and mortality. Here, we determined that activation of nuclear factor erythroid-2-related factor 2 (NRF2) signaling enhances hematopoietic stem progenitor cell (HSPC) function and mitigates IR-induced myelosuppression and mortality. Augmenting NRF2 signaling in mice, either by genetic deletion of the NRF2 inhibitor Keap1 or by pharmacological NRF2 activation with 2-trifluoromethyl-2′-methoxychalone (TMC), enhanced hematopoietic reconstitution following bone marrow transplantation (BMT). Strikingly, even 24 hours after lethal IR exposure, oral administration of TMC mitigated myelosuppression and mortality in mice. Furthermore, TMC administration to irradiated transgenic Notch reporter mice revealed activation of Notch signaling in HSPCs and enhanced HSPC expansion by increasing Jagged1 expression in BM stromal cells. Administration of a Notch inhibitor ablated the effects of TMC on hematopoietic reconstitution. Taken together, we identified a mechanism by which NRF2-mediated Notch signaling improves HSPC function and myelosuppression following IR exposure. Our data indicate that targeting this pathway may provide a countermeasure against the damaging effects of IR exposure.

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“…20,21 Whereas LSK defines the basic marker set used to identify the HSCs, additional markers, such as CD34, CD38, CD48, CD150, and Flt3, are also used in conjunction to further refine HSCs. [22][23][24][25][26] Some investigators also use rhodamine staining or Hoechst dye efflux side population to identify the stem cell population. 26 Most of our understanding about p53 regulation and stress response comes from a series of genetically engineered mouse models generated during the past 2 decades.…”

Section: Introductionmentioning

confidence: 99%

“…[22][23][24][25][26] Some investigators also use rhodamine staining or Hoechst dye efflux side population to identify the stem cell population. 26 Most of our understanding about p53 regulation and stress response comes from a series of genetically engineered mouse models generated during the past 2 decades. In this review, we discuss models that disrupt the p53 pathway that expand our understanding of p53-mediated stress and tissue-dependent cell fate decisions in hematopoiesis.…”

Section: Introductionmentioning

confidence: 99%

The p53 pathway in hematopoiesis: lessons from mouse models, implications for humans

Pant¹,

Quintás‐Cardama

Lozano³

2012

Blood

108

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Aberrations in the p53 tumor suppressor pathway are associated with hematologic malignancies. p53-dependent cell cycle control, senescence, and apoptosis functions are actively involved in maintaining hematopoietic homeostasis under normal and stress conditions. Whereas loss of p53 function promotes leukemia and lymphoma development in humans and mice, increased p53 activity inhibits hematopoietic stem cell function and results in myelodysplasia. Thus, exquisite regulation of p53 activity is critical for homeostasis. Most of our understanding of p53 function in hematopoiesis is derived from genetically engineered mice. Here we summarize some of these models, the various mechanisms that disrupt the regulation of p53 activity, and their relevance to human disease.

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Flow cytometry analysis of murine hematopoietic stem cells

Cited by 110 publications

References 42 publications

Altered Immunity and Dendritic Cell Activity in the Periphery of Mice after Long-Term Engraftment with Bone Marrow from Ultraviolet-Irradiated Mice

Altered Immunity and Dendritic Cell Activity in the Periphery of Mice after Long-Term Engraftment with Bone Marrow from Ultraviolet-Irradiated Mice

NRF2-mediated Notch pathway activation enhances hematopoietic reconstitution following myelosuppressive radiation

The p53 pathway in hematopoiesis: lessons from mouse models, implications for humans

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