Regulation of stress-induced hematopoiesis

Anderson, Georgina; Rodriguez, Melanie; Kathrein, Katie L.

doi:10.1097/moh.0000000000000589

Cited by 12 publications

(7 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The other GO clusters of skeletal system development (GO:0001501) and muscle structure development (GO:0061061) were related to morphological body frame structure and meat production [64]. Candidate genes clustered into the cellular response to misfolded proteins (GO:0071218) and regulation of hemopoiesis (GO:1903706) are thought to be particularly important for environmental stress regulation [65,66].…”

Section: Annotation Of Candidate Selection Signaturesmentioning

confidence: 99%

Whole Genome Resequencing Reveals Genetic Diversity and Selection Signatures of Ethiopian Indigenous Cattle Adapted to Local Environments

et al. 2023

View full text Add to dashboard Cite

Cattle are among the most important domesticated bovid species in the world, of which Ethiopia possesses large populations adapted to different agro-ecologies and production systems. Though several molecular population genetic studies have been done on Ethiopian indigenous cattle, genomic diversity and selection signatures pertinent to adaptation to the different local environments have yet to be comprehensively characterized. Here, the whole genome sequences of 151 samples from 14 Ethiopian indigenous cattle populations were analyzed to assess genomic diversity and differentiation as well as signatures of positive selection (using Hp, iHS, FST, and XP-CLR) in comparison to Sudanese zebu, Asian zebu, Ankole, and African and European taurine cattle. High genomic differentiation was observed between Ethiopian and non-Ethiopian cattle populations, while low genomic differentiation and inbreeding were present between and within Ethiopian cattle populations. Sixteen genome regions overlapping with 40 candidate genes were commonly identified by at least three genome scan methods. High frequencies of missense SNPs in ITPR2, CHADL, GNAS, STING1, and KIT genes with high haplotype differentiations were observed in Ethiopian cattle compared to non-Ethiopian cattle. The candidate genes were significantly associated with several biological functions and molecular pathways responsible for nutrient metabolism, skeletal development, immune response, reproduction, water balance, coat color pigmentation, and circulatory homeostasis. Our results provide new insights into the adaptation of the Ethiopian indigenous cattle to the country’s diverse environments.

show abstract

Section: Annotation Of Candidate Selection Signaturesmentioning

confidence: 99%

Whole Genome Resequencing Reveals Genetic Diversity and Selection Signatures of Ethiopian Indigenous Cattle Adapted to Local Environments

et al. 2023

View full text Add to dashboard Cite

show abstract

“…HSCs must quickly respond to the stimuli such as viral infections, chemotherapy or irradiation to increase their expansion and differentiation in order to replenish immune and blood systems without stem cell pool depletion [ 51 , 52 ]. We used radiation as a stressor to explore whether TXN1 could enhance the potency of HSPCs in response to the injury.…”

Section: Resultsmentioning

confidence: 99%

Thioredoxin-1 regulates self-renewal and differentiation of murine hematopoietic stem cells through p53 tumor suppressor

et al. 2022

View full text Add to dashboard Cite

Background Thioredoxin-1 (TXN1) is one of the major cellular antioxidants in mammals and is involved in a wide range of physiological cellular responses. However, little is known about the roles and the underlying molecular mechanisms of TXN1 in the regulation of hematopoietic stem/progenitor cells (HSPCs). Methods TXN1 conditional knockout mice (ROSA-CreER-TXN1fl/fl) and TXN1fl/fl control mice were used. The mice were treated with tamoxifen and the number and biological functions of HSPCs were measured by flow cytometry, PCR and western blot. Limiting dilution competitive transplantation with sorted HSCs and serial transplantations were performed to assess the effects of TXN1 knockout on HSC self-renewal and long-term reconstitutional capacity. RNA sequencing (RNA-seq) was performed to investigate the downstream molecular pathways of TXN1 deletion in murine HSPCs. CRISPR/Cas9 knockout experiments were performed in vitro in EML murine hematopoietic stem/progenitor cell line to investigate the effects of TXN1 and/or TP53 deletion on cell survival, senescence and colony forming units. TP53 protein degradation assay, CHiP PCR and PGL3 firefly/renilla reporter assay were performed. The effects of TXN1 on various molecular pathways relevant to HSC radiation protection were examined in vitro and in vivo. Results TXN1-TP53 tumor suppressor axis regulates HSPC biological fitness. Deletion of TXN1 in HSPCs using in vivo and in vitro models activates TP53 signaling pathway, and attenuates HSPC capacity to reconstitute hematopoiesis. Furthermore, we found that knocking out of TXN1 renders HSPCs more sensitive to radiation and treatment with recombinant TXN1 promotes the proliferation and expansion of HSPCs. Conclusions Our findings suggest that TXN1-TP53 axis acts as a regulatory mechanism in HSPC biological functions. Additionally, our study demonstrates the clinical potential of TXN1 for enhancing hematopoietic recovery in hematopoietic stem cell transplant and protecting HSPCs from radiation injury.

show abstract

“…In both ≥0.3 and ≥0.7 loading analyses, three factors were found in the PreVPo analysis ( Figures 2 , 5 ). For the ≥0.3 analysis ( Figure 2 ), factor 1 was made up of a grouping of proinflammatory cytokines that included primarily CC chemokines (MDC, Eotaxin, RANTES, MCP3, MIP1a), cytokines (IL-4, IL-9, IL-18, etc) and one strong CXC chemokine (IL-8) as well as markers associated with central hematopoiesis [Flt3, IL-5, GMCSF, IL-7 ( 23 )]. In factor 2, there is pattern of pro-inflammatory cytokines including some CXC chemokines (IP10, Gro-alpha, fractalkine) with an addition of some anti-inflammatory markers (IL-10), steroid and thyroid hormones, along with peripheral hematopoietic markers as well (PDGFAA, VEGF).…”

Section: Discussionmentioning

confidence: 99%

Principal component analysis of salivary cytokines and hormones in the acute stress response

et al. 2022

View full text Add to dashboard Cite

The acute stress response is characterized by activation of multiple interconnected systems in the body, resulting in the release of a flood of hormones and immune mediators into circulation. In addition to detection of these molecules in the serum, saliva can serve as a source of these markers as well and can be collected in a non-invasive way. The complete profile of salivary biomarkers associated with the hypothalamic pituitary adrenal/gonadal axes and the immune system during the acute stress response has not been fully elucidated. In a cohort of 62 first responders engaged in a stress training exercise, we set out to determine patterns of cytokine, chemokine and hormone shifts during the acute stress response. Salivary samples were collected immediately before (pre-stress), immediately after (post-stress) and 1 h after the stress test (recovery). Multiplex ELISA panels of 42 cytokines and 6 steroid and thyroid hormones were used to determine concentrations of these biomarkers during the three aforementioned time points. Principal components analysis was conducted to determine patterns in the large data sets collected. In our ≥0.3 loading principal components analysis, for pre-stress vs. post, post-stress vs. recovery and pre-stress vs. recovery, a total of three, four and three factors accounted for 56.6, 68.34, and 61.70% of the biomarker variation for each phase respectively. In the ≥0.7 loading principal components analysis, three, four and three factors were found for pre-stress vs. post, post-stress vs. recovery and pre-stress vs. recovery stages, respectively. Of note, in our ≥0.3 loading principal components analysis, MCP1 was present in all three factors from pre-stress to post-stress, and fractalkine was found to be in all four factors post-stress vs. recovery and pre vs. recovery from stress. Additionally, hormones testosterone, estradiol, T4 and T3 grouped together consistently in the same factor for all phases of acute stress in both ≥0.3 and ≥0.7 principal components analysis. Overall, our results identified specific patterns of immune markers and hormones that shift during acute stress and warrant further investigation to understand their mechanistic role in regulating the stress response.

show abstract

Regulation of stress-induced hematopoiesis

Cited by 12 publications

References 71 publications

Whole Genome Resequencing Reveals Genetic Diversity and Selection Signatures of Ethiopian Indigenous Cattle Adapted to Local Environments

Whole Genome Resequencing Reveals Genetic Diversity and Selection Signatures of Ethiopian Indigenous Cattle Adapted to Local Environments

Thioredoxin-1 regulates self-renewal and differentiation of murine hematopoietic stem cells through p53 tumor suppressor

Principal component analysis of salivary cytokines and hormones in the acute stress response

Contact Info

Product

Resources

About