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S100A6 is a critical regulator of hematopoietic stem cells.

Tan Grahn, Hooi Min (author)
Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hematopoes och genterapi,Forskargrupper vid Lunds universitet,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Hematopoiesis and Gene Therapy,Lund University Research Groups,Lund Univ Hosp, Sweden
Niroula, Abhishek (author)
Lund University,Lunds universitet,Proteinbioinformatik,Forskargrupper vid Lunds universitet,Hematogenomics,Protein Bioinformatics,Lund University Research Groups,Lund Univ, Sweden
Vegvari, Akos (author)
Karolinska Institutet,Karolinska Inst, Sweden
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Oburoglu, Leal (author)
Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Blodstamcellsutveckling,Forskargrupper vid Lunds universitet,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Hematopoietic Stem Cell Development,Lund University Research Groups,Lund Univ Hosp, Sweden
Pertesi, Maroulio (author)
Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hematogenomics,Forskargrupper vid Lunds universitet,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Lund University Research Groups,Lund Univ, Sweden
Warsi, Sarah (author)
Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hematopoes och genterapi,Forskargrupper vid Lunds universitet,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Hematopoiesis and Gene Therapy,Lund University Research Groups,Lund Univ Hosp, Sweden
Safi, Fatemeh (author)
Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cells and Leukemia,Forskargrupper vid Lunds universitet,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,Lund University Research Groups,Skåne University Hospital,Lund Univ Hosp, Sweden
Miharada, Natsumi (author)
Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hematogenomics,Forskargrupper vid Lunds universitet,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Lund University Research Groups,Lund Univ Hosp, Sweden
C. Garcia, Sandra (author)
University of California, Los Angeles,Univ Calif Los Angeles, CA USA
Siva, Kavitha (author)
Lund University,Lunds universitet,Stamceller till röda blodkroppar,Forskargrupper vid Lunds universitet,Stem Cells to Red Blood Cells,Lund University Research Groups,Lund Univ Hosp, Sweden
Liu, Yang (author)
Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hematopoes och genterapi,Forskargrupper vid Lunds universitet,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Hematopoiesis and Gene Therapy,Lund University Research Groups,Lund Univ Hosp, Sweden
Rörby, Emma (author)
Linköpings universitet,Linköping University,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten
Nilsson, Björn (author)
Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hematogenomics,Forskargrupper vid Lunds universitet,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Lund University Research Groups,Lund Univ, Sweden
Zubarev, Roman A. (author)
Karolinska Institutet,Karolinska Inst, Sweden
Karlsson, Stefan (author)
Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hematopoes och genterapi,Forskargrupper vid Lunds universitet,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Hematopoiesis and Gene Therapy,Lund University Research Groups,Lund Univ Hosp, Sweden
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 (creator_code:org_t)
2020-06-19
2020
English.
In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551.
Related links:
http://dx.doi.org/10... (free)
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https://www.nature.c...
http://10.1038/s4137...
https://liu.diva-por... (primary) (Raw object)
https://lup.lub.lu.s...
https://doi.org/10.1...
http://kipublication...
https://urn.kb.se/re...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • The fate options of hematopoietic stem cells (HSCs) include self-renewal, differentiation, migration, and apoptosis. HSCs self-renewal divisions in stem cells are required for rapid regeneration during tissue damage and stress, but how precisely intracellular calcium signals are regulated to maintain fate options in normal hematopoiesis is unclear. S100A6 knockout (KO) HSCs have reduced total cell numbers in the HSC compartment, decreased myeloid output, and increased apoptotic HSC numbers in steady state. S100A6KO HSCs had impaired self-renewal and regenerative capacity, not responding to 5-Fluorouracil. Our transcriptomic and proteomic profiling suggested that S100A6 is a critical HSC regulator. Intriguingly, S100A6KO HSCs showed decreased levels of phosphorylated Akt (p-Akt) and Hsp90, with an impairment of mitochondrial respiratory capacity and a reduction of mitochondrial calcium levels. We showed that S100A6 regulates intracellular and mitochondria calcium buffering of HSC upon cytokine stimulation and have demonstrated that Akt activator SC79 reverts the levels of intracellular and mitochondrial calcium in HSC. Hematopoietic colony-forming activity and the Hsp90 activity of S100A6KO are restored through activation of the Akt pathway. We show that p-Akt is the prime downstream mechanism of S100A6 in the regulation of HSC self-renewal by specifically governing mitochondrial metabolic function and Hsp90 protein quality.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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