Bile Acids Protect Expanding Hematopoietic Stem Cells from Unfolded Protein Stress in Fetal Liver.

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Sigurdsson, ValgardurLund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellsmetabolism,Forskargrupper vid Lunds universitet,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Metabolism,Lund University Research Groups (author)

Bile Acids Protect Expanding Hematopoietic Stem Cells from Unfolded Protein Stress in Fetal Liver.

Article/chapterEnglish2016

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Elsevier BV,2016

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LIBRIS-ID:oai:lup.lub.lu.se:1ece2107-a8be-47d3-afdc-718f85d6dcb4
https://lup.lub.lu.se/record/8830041URI
https://doi.org/10.1016/j.stem.2016.01.002DOI

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Language:English
Summary in:English

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During development, hematopoietic stem cells (HSCs) undergo a rapid expansion in the fetal liver (FL) before settling in the adult bone marrow. We recently reported that proliferating adult HSCs are vulnerable to ER stress caused by accumulation of mis-folded proteins. Here, we find that FL-HSCs, despite an increased protein synthesis rate and a requirement for protein folding, do not upregulate ER chaperones. Instead, bile acids (BAs), secreted from maternal and fetal liver, coordinate to serve as chemical chaperones. Taurocholic acid, the major BA in FL, supports growth of HSCs in vitro by inhibiting protein aggregation. In vivo, reducing BA levels leads to ER stress elevation and accumulation of aggregated proteins and significantly decreases the number of FL-HSCs. Taken together, these findings reveal that BA alleviation of ER stress is a mechanism required for HSC expansion during fetal hematopoiesis.

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Takei, Hajime (author)
Soboleva, SvetlanaLund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellsmetabolism,Forskargrupper vid Lunds universitet,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Metabolism,Lund University Research Groups(Swepub:lu)med-sts (author)
Radulovic, VisnjaLund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellsmetabolism,Forskargrupper vid Lunds universitet,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Metabolism,Lund University Research Groups(Swepub:lu)med-var (author)
Galeev, RomanLund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-rng (author)
Siva, KavithaLund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-kvs (author)
Leeb-Lundberg, FredrikLund University,Lunds universitet,Drug Target Discovery,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)mphy-fle (author)
Iida, Takashi (author)
Nittono, Hiroshi (author)
Miharada, KenichiLund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellsmetabolism,Forskargrupper vid Lunds universitet,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Metabolism,Lund University Research Groups(Swepub:lu)med-kmh (author)
Avdelningen för molekylärmedicin och genterapiInstitutionen för laboratoriemedicin (creator_code:org_t)

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In:Cell Stem Cell: Elsevier BV18:4, s. 32-5221934-5909

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