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| 2. |
- Wray, Jason P., et al.
(författare)
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Regulome analysis in B-acute lymphoblastic leukemia exposes Core Binding Factor addiction as a therapeutic vulnerability
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The ETV6-RUNX1 onco-fusion arises in utero, initiating a clinically silent pre-leukemic state associated with the development of pediatric B-acute lymphoblastic leukemia (B-ALL). We characterize the ETV6-RUNX1 regulome by integrating chromatin immunoprecipitation- and RNA-sequencing and show that ETV6-RUNX1 functions primarily through competition for RUNX1 binding sites and transcriptional repression. In pre-leukemia, this results in ETV6-RUNX1 antagonization of cell cycle regulation by RUNX1 as evidenced by mass cytometry analysis of B-lineage cells derived from ETV6-RUNX1 knock-in human pluripotent stem cells. In frank leukemia, knockdown of RUNX1 or its co-factor CBFβ results in cell death suggesting sustained requirement for RUNX1 activity which is recapitulated by chemical perturbation using an allosteric CBFβ-inhibitor. Strikingly, we show that RUNX1 addiction extends to other genetic subtypes of pediatric B-ALL and also adult disease. Importantly, inhibition of RUNX1 activity spares normal hematopoiesis. Our results suggest that chemical intervention in the RUNX1 program may provide a therapeutic opportunity in ALL.
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| 3. |
- Karlsson, Göran, et al.
(författare)
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The Tetraspanin CD9 Affords High-Purity Capture of All Murine Hematopoietic Stem Cells
- 2013
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 4:4, s. 642-648
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Tidskriftsartikel (refereegranskat)abstract
- Prospective isolation is critical for understanding the cellular and molecular aspects of stem cell heterogeneity. Here, we identify the cell surface antigen CD9 as a positive marker that provides a simple alternative for hematopoietic stem cell isolation at high purity. Crucially, CD9 affords the capture of all hematopoietic stem cells in murine bone marrow in the absence of contaminating populations that lack authentic stem cell function. Using CD9 as a tool to subdivide hematopoietic stem-cell-containing populations, we provide evidence for heterogeneity at the cellular, functional, and molecular levels.
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| 4. |
- Kyriakidis, Miltos, et al.
(författare)
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A human factors perspective on automated driving
- 2019
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Ingår i: Theoretical Issues in Ergonomics Science. - : Taylor & Francis. - 1463-922X .- 1464-536X. ; 20:3, s. 223-249
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Tidskriftsartikel (refereegranskat)abstract
- Automated driving can fundamentally change road transportation and improve quality of life. However, at present, the role of humans in automated vehicles (AVs) is not clearly established. Interviews were conducted in April and May 2015 with 12 expert researchers in the field of human factors (HFs) of automated driving to identify commonalities and distinctive perspectives regarding HF challenges in the development of AVs. The experts indicated that an AV up to SAE Level 4 should inform its driver about the AV's capabilities and operational status, and ensure safety while changing between automated and manual modes. HF research should particularly address interactions between AVs, human drivers and vulnerable road users. Additionally, driver-training programmes may have to be modified to ensure that humans are capable of using AVs. Finally, a reflection on the interviews is provided, showing discordance between the interviewees’ statements – which appear to be in line with a long history of HFs research – and the rapid development of automation technology. We expect our perspective to be instrumental for stakeholders involved in AV development and instructive to other parties.
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