Sökning: WFRF:(Mattebo Alexander) >
Prospective isolati...
Prospective isolation of radiation induced erythroid stress progenitors reveals unique transcriptomic and epigenetic signatures enabling increased erythroid output
-
- Singbrant, Sofie (författare)
- Lund University,Lunds universitet,Stem cell and red cell biology,Forskargrupper vid Lunds universitet,Lund University Research Groups
-
- Mattebo, Alexander (författare)
- Lund University,Lunds universitet,Stamceller till röda blodkroppar,Forskargrupper vid Lunds universitet,Stem Cells to Red Blood Cells,Lund University Research Groups
-
- Sigvardsson, Mikael (författare)
- Lund University,Lunds universitet,Molekylär lymfopoes,Forskargrupper vid Lunds universitet,Molecular Lymphopoiesis,Lund University Research Groups
-
visa fler...
-
- Strid, Tobias (författare)
- Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine
-
- Flygare, Johan (författare)
- Lund University,Lunds universitet,Stamceller till röda blodkroppar,Forskargrupper vid Lunds universitet,Stem Cells to Red Blood Cells,Lund University Research Groups
-
visa färre...
-
(creator_code:org_t)
- 2020-01-09
- 2020
- Engelska 11 s.
-
Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 105:11, s. 2561-2571
- Relaterad länk:
-
http://dx.doi.org/10... (free)
-
visa fler...
-
https://haematologic...
-
https://lup.lub.lu.s...
-
https://doi.org/10.3...
-
visa färre...
Abstract
Ämnesord
Stäng
- Massive expansion of erythroid progenitor cells is essential for surviving anemic stress. Research towards understanding this critical process, referred to as stress-erythropoiesis, has been hampered due to the lack of specific marker-combinations enabling analysis of the distinct stress-progenitor cells capable of providing radioprotection and enhanced red blood cell production. Here we present a method for the precise identification and in vivo validation of progenitor cells contributing to both steady-state and stress-erythropoiesis, enabling for the first time in-depth molecular characterization of these cells. Differential expression of surface markers CD150, CD9 and Sca1 defines a hierarchy of splenic stress-progenitors during irradiation-induced stress recovery in mice, and provides high-purity isolation of the functional stress erythroid burst-forming-units (stress-BFU-E) with a 100-fold improved enrichment compared to the state-of-the-art. By transplanting purified stress-progenitors expressing the fluorescent protein Kusabira Orange, we determined their kinetics in vivo and demonstrated that CD150+CD9+Sca1 -stress-BFU-E provide a massive but transient radioprotective erythroid wave, followed by multi-lineage reconstitution from CD150+CD9+Sca1+ multi-potent stem/progenitor cells. Whole genome transcriptional analysis revealed that stress-BFU-E express gene signatures more associated with erythropoiesis and proliferation compared to steady-state BFU-E, and are bone morphogenetic protein 4-responsive. Evaluation of chromatin accessibility through ATAC sequencing reveals enhanced and differential accessibility to binding sites of the chromatin-looping transcription factor CTCF in stress-BFU-E compared to steady-state BFU-E. Our findings offer a molecular insight into the unique capacity of stress-BFU-E to rapidly form erythroid cells in response to anemia and constitute an important step towards identifying novel erythropoiesis stimulating agents.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas