Continuous mitotic activity of primitive hematopoietic stem cells in adult mice

The proliferative activity of aging hematopoietic stem cells (HSCs) is controversially discussed. Inducible fluorescent histone 2B fusion protein (H2B-FP) transgenic mice are important tools for tracking the mitotic history of murine HSCs in label dilution experiments. A recent study proposed that p...

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Published in	The Journal of experimental medicine Vol. 217; no. 6
Main Authors	Morcos, Mina N.F., Zerjatke, Thomas, Glauche, Ingmar, Munz, Clara M., Ge, Yan, Petzold, Andreas, Reinhardt, Susanne, Dahl, Andreas, Anstee, Natasha S., Bogeska, Ruzhica, Milsom, Michael D., Säwén, Petter, Wan, Haixia, Bryder, David, Roers, Axel, Gerbaulet, Alexander
Format	Journal Article
Language	English
Published	United States Rockefeller University Press 01.06.2020
Subjects	Aging - physiology Animals cd34 Clinical Medicine dynamics exchange Fluorescence Gene Expression Regulation gene-expression Hematologi Hematology Hematopoiesis Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - metabolism heterogeneity Histones - metabolism history Immunologi inom det medicinska området Immunology Immunology in the Medical Area Kinetics Klinisk medicin Medical and Health Sciences Medicin och hälsovetenskap Mice, Inbred C57BL Mitosis Models, Biological proliferation Proteolysis Recombinant Fusion Proteins - metabolism Research & Experimental Medicine self-renewal Stem Cells & Regeneration
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ISSN	0022-1007 1540-9538 1540-9538
DOI	10.1084/jem.20191284

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Abstract	The proliferative activity of aging hematopoietic stem cells (HSCs) is controversially discussed. Inducible fluorescent histone 2B fusion protein (H2B-FP) transgenic mice are important tools for tracking the mitotic history of murine HSCs in label dilution experiments. A recent study proposed that primitive HSCs symmetrically divide only four times to then enter permanent quiescence. We observed that background fluorescence due to leaky H2B-FP expression, occurring in all H2B-FP transgenes independent of label induction, accumulated with age in HSCs with high repopulation potential. We argue that this background had been misinterpreted as stable retention of induced label. We found cell division–independent half-lives of H2B-FPs to be short, which had led to overestimation of HSC divisional activity. Our data do not support abrupt entry of HSCs into permanent quiescence or sudden loss of regeneration potential after four divisions, but show that primitive HSCs of adult mice continue to cycle rarely.
AbstractList	The proliferative activity of aging hematopoietic stem cells (HSCs) is controversially discussed. Inducible fluorescent histone 2B fusion protein (H2B-FP) transgenic mice are important tools for tracking the mitotic history of murine HSCs in label dilution experiments. A recent study proposed that primitive HSCs symmetrically divide only four times to then enter permanent quiescence. We observed that background fluorescence due to leaky H2B-FP expression, occurring in all H2B-FP transgenes independent of label induction, accumulated with age in HSCs with high repopulation potential. We argue that this background had been misinterpreted as stable retention of induced label. We found cell division-independent half-lives of H2B-FPs to be short, which had led to overestimation of HSC divisional activity. Our data do not support abrupt entry of HSCs into permanent quiescence or sudden loss of regeneration potential after four divisions, but show that primitive HSCs of adult mice continue to cycle rarely. Morcos et al. show that there is no evidence for abrupt entry of aging hematopoietic stem cells into quiescence after four divisions as previously suggested. They examine factors confounding pulse-chase experiments in H2B-fusion protein transgenic mice that can lead to misinterpretations of HSC proliferative behavior. The proliferative activity of aging hematopoietic stem cells (HSCs) is controversially discussed. Inducible fluorescent histone 2B fusion protein (H2B-FP) transgenic mice are important tools for tracking the mitotic history of murine HSCs in label dilution experiments. A recent study proposed that primitive HSCs symmetrically divide only four times to then enter permanent quiescence. We observed that background fluorescence due to leaky H2B-FP expression, occurring in all H2B-FP transgenes independent of label induction, accumulated with age in HSCs with high repopulation potential. We argue that this background had been misinterpreted as stable retention of induced label. We found cell division–independent half-lives of H2B-FPs to be short, which had led to overestimation of HSC divisional activity. Our data do not support abrupt entry of HSCs into permanent quiescence or sudden loss of regeneration potential after four divisions, but show that primitive HSCs of adult mice continue to cycle rarely. The proliferative activity of aging hematopoietic stem cells (HSCs) is controversially discussed. Inducible fluorescent histone 2B fusion protein (H2B-FP) transgenic mice are important tools for tracking the mitotic history of murine HSCs in label dilution experiments. A recent study proposed that primitive HSCs symmetrically divide only four times to then enter permanent quiescence. We observed that background fluorescence due to leaky H2B-FP expression, occurring in all H2B-FP transgenes independent of label induction, accumulated with age in HSCs with high repopulation potential. We argue that this background had been misinterpreted as stable retention of induced label. We found cell division-independent half-lives of H2B-FPs to be short, which had led to overestimation of HSC divisional activity. Our data do not support abrupt entry of HSCs into permanent quiescence or sudden loss of regeneration potential after four divisions, but show that primitive HSCs of adult mice continue to cycle rarely.The proliferative activity of aging hematopoietic stem cells (HSCs) is controversially discussed. Inducible fluorescent histone 2B fusion protein (H2B-FP) transgenic mice are important tools for tracking the mitotic history of murine HSCs in label dilution experiments. A recent study proposed that primitive HSCs symmetrically divide only four times to then enter permanent quiescence. We observed that background fluorescence due to leaky H2B-FP expression, occurring in all H2B-FP transgenes independent of label induction, accumulated with age in HSCs with high repopulation potential. We argue that this background had been misinterpreted as stable retention of induced label. We found cell division-independent half-lives of H2B-FPs to be short, which had led to overestimation of HSC divisional activity. Our data do not support abrupt entry of HSCs into permanent quiescence or sudden loss of regeneration potential after four divisions, but show that primitive HSCs of adult mice continue to cycle rarely.
Author	Munz, Clara M. Glauche, Ingmar Säwén, Petter Dahl, Andreas Wan, Haixia Petzold, Andreas Gerbaulet, Alexander Anstee, Natasha S. Bryder, David Zerjatke, Thomas Morcos, Mina N.F. Roers, Axel Reinhardt, Susanne Ge, Yan Bogeska, Ruzhica Milsom, Michael D.
AuthorAffiliation	1 Institute for Immunology, Faculty of Medicine, TU Dresden, Dresden, Germany 5 Division of Molecular Hematology, Lund University, Lund, Sweden 2 Institute for Medical Informatics and Biometry, Faculty of Medicine, TU Dresden, Dresden, Germany 4 Division of Experimental Hematology, Deutsches Krebsforschungszentrum and Heidelberg Institute for Stem Cell Technology and Experimental Medicine, Heidelberg, Germany 6 Sahlgrenska Cancer Centre, Gothenburg University, Gothenburg, Sweden 3 DRESDEN-concept Genome Center, Center for Molecular and Cellular Bioengineering, TU Dresden, Dresden, Germany
AuthorAffiliation_xml	– name: 5 Division of Molecular Hematology, Lund University, Lund, Sweden – name: 1 Institute for Immunology, Faculty of Medicine, TU Dresden, Dresden, Germany – name: 4 Division of Experimental Hematology, Deutsches Krebsforschungszentrum and Heidelberg Institute for Stem Cell Technology and Experimental Medicine, Heidelberg, Germany – name: 6 Sahlgrenska Cancer Centre, Gothenburg University, Gothenburg, Sweden – name: 3 DRESDEN-concept Genome Center, Center for Molecular and Cellular Bioengineering, TU Dresden, Dresden, Germany – name: 2 Institute for Medical Informatics and Biometry, Faculty of Medicine, TU Dresden, Dresden, Germany
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Cites_doi	10.1038/nature06115 10.1016/S0960-9822(98)70156-3 10.1016/j.cell.2005.05.026 10.1182/blood.V78.5.1237.1237 10.1146/annurev.genet.36.041002.120114 10.1038/nature12830 10.1038/nbt.1517 10.1016/j.stem.2013.05.014 10.1172/JCI28310 10.1016/j.stemcr.2017.04.012 10.1084/jem.20101643 10.1093/nar/gkx1098 10.1084/jem.20131115 10.1016/j.cell.2013.07.037 10.1016/j.celrep.2016.02.073 10.1038/nature05879 10.1038/nprot.2008.211 10.1182/blood-2014-12-570200 10.1038/nature13824 10.1182/blood-2008-12-192054 10.1093/bioinformatics/btw777 10.1126/science.1092436 10.1182/blood-2016-03-706010 10.1038/emboj.2008.72 10.1038/nature12932 10.1073/pnas.1000834107 10.1371/journal.pone.0002357 10.1182/blood.V94.8.2548.420k38_2548_2554 10.1083/jcb.122.4.897 10.1182/blood-2015-10-676072 10.1016/j.cell.2016.10.022 10.1083/jcb.153.7.1341 10.1084/jem.20050967 10.15252/embj.201488017 10.1016/j.stemcr.2014.01.016 10.1073/pnas.87.19.7433 10.1126/science.273.5272.242 10.1371/journal.pcbi.1000447 10.1084/jem.20131128 10.1182/blood-2002-02-0355 10.1016/j.stem.2015.04.004 10.1002/gene.20180 10.1093/bioinformatics/btq057 10.1038/nrm3941 10.1016/j.cell.2008.10.048 10.1371/journal.pone.0006972 10.1146/annurev-immunol-032414-112019 10.1093/bioinformatics/btt656 10.1038/nature14242 10.1016/j.molcel.2007.01.019
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Copyright	2020 Morcos et al. 2020 Morcos et al. 2020
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References	Säwén (2023072617371373700_bib35) 2016; 14 Egli (2023072617371373700_bib9) 2007; 447 Nakada (2023072617371373700_bib28) 2014; 505 Eaves (2023072617371373700_bib8) 2015; 125 Sun (2023072617371373700_bib40) 2014; 514 Venkatesh (2023072617371373700_bib45) 2015; 16 Kiel (2023072617371373700_bib21) 2005; 121 Radomska (2023072617371373700_bib33) 2002; 100 Kiel (2023072617371373700_bib22) 2007; 449 Shin (2023072617371373700_bib38) 2014; 211 Takizawa (2023072617371373700_bib41) 2011; 208 Wu (2023072617371373700_bib49) 2010; 26 Harrison (2023072617371373700_bib15) 1991; 78 Basak (2023072617371373700_bib1) 2014; 33 Fleming (2023072617371373700_bib10) 1993; 122 Gossen (2023072617371373700_bib13) 2002; 36 Wilson (2023072617371373700_bib47) 2008; 135 Spangrude (2023072617371373700_bib39) 1990; 87 Kimura (2023072617371373700_bib23) 2001; 153 Busch (2023072617371373700_bib6) 2015; 518 Höfer (2023072617371373700_bib16) 2016; 34 Bowie (2023072617371373700_bib5) 2006; 116 Morcos (2023072617371373700_bib27) 2017; 8 Jamai (2023072617371373700_bib18) 2007; 25 Oguro (2023072617371373700_bib29) 2013; 13 Bernitz (2023072617371373700_bib4) 2016; 167 Glauche (2023072617371373700_bib12) 2009; 5 Qiu (2023072617371373700_bib32) 2014; 2 Osawa (2023072617371373700_bib30) 1996; 273 Kent (2023072617371373700_bib20) 2009; 113 Zerbino (2023072617371373700_bib50) 2018; 46 Toyama (2023072617371373700_bib42) 2013; 154 van der Wath (2023072617371373700_bib44) 2009; 4 Foudi (2023072617371373700_bib11) 2009; 27 McCarthy (2023072617371373700_bib26) 2017; 33 Sheikh (2023072617371373700_bib37) 2016; 128 Tumbar (2023072617371373700_bib43) 2004; 303 Waghmare (2023072617371373700_bib46) 2008; 27 Wilson (2023072617371373700_bib48) 2015; 16 Beard (2023072617371373700_bib2) 2006; 44 Passegué (2023072617371373700_bib31) 2005; 202 Schoedel (2023072617371373700_bib36) 2016; 128 Beerman (2023072617371373700_bib3) 2010; 107 Kanda (2023072617371373700_bib19) 1998; 8 Liao (2023072617371373700_bib25) 2014; 30 Sato (2023072617371373700_bib34) 1999; 94 Grinenko (2023072617371373700_bib14) 2014; 211 Li (2023072617371373700_bib24) 2013; 504 Huang (2023072617371373700_bib17) 2009; 4 Challen (2023072617371373700_bib7) 2008; 3
References_xml	– volume: 449 start-page: 238 year: 2007 ident: 2023072617371373700_bib22 article-title: Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU publication-title: Nature. doi: 10.1038/nature06115 – volume: 8 start-page: 377 year: 1998 ident: 2023072617371373700_bib19 article-title: Histone-GFP fusion protein enables sensitive analysis of chromosome dynamics in living mammalian cells publication-title: Curr. Biol. doi: 10.1016/S0960-9822(98)70156-3 – volume: 121 start-page: 1109 year: 2005 ident: 2023072617371373700_bib21 article-title: SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells publication-title: Cell. doi: 10.1016/j.cell.2005.05.026 – volume: 78 start-page: 1237 year: 1991 ident: 2023072617371373700_bib15 article-title: Most primitive hematopoietic stem cells are stimulated to cycle rapidly after treatment with 5-fluorouracil publication-title: Blood. doi: 10.1182/blood.V78.5.1237.1237 – volume: 36 start-page: 153 year: 2002 ident: 2023072617371373700_bib13 article-title: Studying gene function in eukaryotes by conditional gene inactivation publication-title: Annu. Rev. Genet. doi: 10.1146/annurev.genet.36.041002.120114 – volume: 504 start-page: 143 year: 2013 ident: 2023072617371373700_bib24 article-title: Oncogenic Nras has bimodal effects on stem cells that sustainably increase competitiveness publication-title: Nature. doi: 10.1038/nature12830 – volume: 27 start-page: 84 year: 2009 ident: 2023072617371373700_bib11 article-title: Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cells publication-title: Nat. Biotechnol. doi: 10.1038/nbt.1517 – volume: 13 start-page: 102 year: 2013 ident: 2023072617371373700_bib29 article-title: SLAM family markers resolve functionally distinct subpopulations of hematopoietic stem cells and multipotent progenitors publication-title: Cell Stem Cell. doi: 10.1016/j.stem.2013.05.014 – volume: 116 start-page: 2808 year: 2006 ident: 2023072617371373700_bib5 article-title: Hematopoietic stem cells proliferate until after birth and show a reversible phase-specific engraftment defect publication-title: J. Clin. Invest. doi: 10.1172/JCI28310 – volume: 8 start-page: 1472 year: 2017 ident: 2023072617371373700_bib27 article-title: SCA-1 Expression Level Identifies Quiescent Hematopoietic Stem and Progenitor Cells publication-title: Stem Cell Reports. doi: 10.1016/j.stemcr.2017.04.012 – volume: 208 start-page: 273 year: 2011 ident: 2023072617371373700_bib41 article-title: Dynamic variation in cycling of hematopoietic stem cells in steady state and inflammation publication-title: J. Exp. Med. doi: 10.1084/jem.20101643 – volume: 46 start-page: D754 year: 2018 ident: 2023072617371373700_bib50 article-title: Ensembl 2018 publication-title: Nucleic Acids Res. doi: 10.1093/nar/gkx1098 – volume: 211 start-page: 209 year: 2014 ident: 2023072617371373700_bib14 article-title: Clonal expansion capacity defines two consecutive developmental stages of long-term hematopoietic stem cells publication-title: J. Exp. Med. doi: 10.1084/jem.20131115 – volume: 154 start-page: 971 year: 2013 ident: 2023072617371373700_bib42 article-title: Identification of long-lived proteins reveals exceptional stability of essential cellular structures publication-title: Cell. doi: 10.1016/j.cell.2013.07.037 – volume: 14 start-page: 2809 year: 2016 ident: 2023072617371373700_bib35 article-title: Mitotic History Reveals Distinct Stem Cell Populations and Their Contributions to Hematopoiesis publication-title: Cell Rep. doi: 10.1016/j.celrep.2016.02.073 – volume: 447 start-page: 679 year: 2007 ident: 2023072617371373700_bib9 article-title: Developmental reprogramming after chromosome transfer into mitotic mouse zygotes publication-title: Nature. doi: 10.1038/nature05879 – volume: 4 start-page: 44 year: 2009 ident: 2023072617371373700_bib17 article-title: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources publication-title: Nat. Protoc. doi: 10.1038/nprot.2008.211 – volume: 125 start-page: 2605 year: 2015 ident: 2023072617371373700_bib8 article-title: Hematopoietic stem cells: concepts, definitions, and the new reality publication-title: Blood. doi: 10.1182/blood-2014-12-570200 – volume: 514 start-page: 322 year: 2014 ident: 2023072617371373700_bib40 article-title: Clonal dynamics of native haematopoiesis publication-title: Nature. doi: 10.1038/nature13824 – volume: 113 start-page: 6342 year: 2009 ident: 2023072617371373700_bib20 article-title: Prospective isolation and molecular characterization of hematopoietic stem cells with durable self-renewal potential publication-title: Blood. doi: 10.1182/blood-2008-12-192054 – volume: 33 start-page: 1179 year: 2017 ident: 2023072617371373700_bib26 article-title: Scater: pre-processing, quality control, normalization and visualization of single-cell RNA-seq data in R publication-title: Bioinformatics. doi: 10.1093/bioinformatics/btw777 – volume: 303 start-page: 359 year: 2004 ident: 2023072617371373700_bib43 article-title: Defining the epithelial stem cell niche in skin publication-title: Science. doi: 10.1126/science.1092436 – volume: 128 start-page: 2285 year: 2016 ident: 2023072617371373700_bib36 article-title: The bulk of the hematopoietic stem cell population is dispensable for murine steady-state and stress hematopoiesis publication-title: Blood. doi: 10.1182/blood-2016-03-706010 – volume: 27 start-page: 1309 year: 2008 ident: 2023072617371373700_bib46 article-title: Quantitative proliferation dynamics and random chromosome segregation of hair follicle stem cells publication-title: EMBO J. doi: 10.1038/emboj.2008.72 – volume: 505 start-page: 555 year: 2014 ident: 2023072617371373700_bib28 article-title: Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy publication-title: Nature. doi: 10.1038/nature12932 – volume: 107 start-page: 5465 year: 2010 ident: 2023072617371373700_bib3 article-title: Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion publication-title: Proc. Natl. Acad. Sci. USA. doi: 10.1073/pnas.1000834107 – volume: 3 year: 2008 ident: 2023072617371373700_bib7 article-title: Promiscuous expression of H2B-GFP transgene in hematopoietic stem cells publication-title: PLoS One. doi: 10.1371/journal.pone.0002357 – volume: 94 start-page: 2548 year: 1999 ident: 2023072617371373700_bib34 article-title: Reversible expression of CD34 by murine hematopoietic stem cells publication-title: Blood. doi: 10.1182/blood.V94.8.2548.420k38_2548_2554 – volume: 122 start-page: 897 year: 1993 ident: 2023072617371373700_bib10 article-title: Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells publication-title: J. Cell Biol. doi: 10.1083/jcb.122.4.897 – volume: 128 start-page: 2307 year: 2016 ident: 2023072617371373700_bib37 article-title: MOZ (KAT6A) is essential for the maintenance of classically defined adult hematopoietic stem cells publication-title: Blood. doi: 10.1182/blood-2015-10-676072 – volume: 167 start-page: 1296 year: 2016 ident: 2023072617371373700_bib4 article-title: Hematopoietic Stem Cells Count and Remember Self-Renewal Divisions publication-title: Cell. doi: 10.1016/j.cell.2016.10.022 – volume: 153 start-page: 1341 year: 2001 ident: 2023072617371373700_bib23 article-title: Kinetics of core histones in living human cells: little exchange of H3 and H4 and some rapid exchange of H2B publication-title: J. Cell Biol. doi: 10.1083/jcb.153.7.1341 – volume: 202 start-page: 1599 year: 2005 ident: 2023072617371373700_bib31 article-title: Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates publication-title: J. Exp. Med. doi: 10.1084/jem.20050967 – volume: 33 start-page: 2057 year: 2014 ident: 2023072617371373700_bib1 article-title: Mapping early fate determination in Lgr5+ crypt stem cells using a novel Ki67-RFP allele publication-title: EMBO J. doi: 10.15252/embj.201488017 – volume: 2 start-page: 473 year: 2014 ident: 2023072617371373700_bib32 article-title: Divisional history and hematopoietic stem cell function during homeostasis publication-title: Stem Cell Reports. doi: 10.1016/j.stemcr.2014.01.016 – volume: 87 start-page: 7433 year: 1990 ident: 2023072617371373700_bib39 article-title: Resting and activated subsets of mouse multipotent hematopoietic stem cells publication-title: Proc. Natl. Acad. Sci. USA. doi: 10.1073/pnas.87.19.7433 – volume: 273 start-page: 242 year: 1996 ident: 2023072617371373700_bib30 article-title: Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell publication-title: Science. doi: 10.1126/science.273.5272.242 – volume: 5 year: 2009 ident: 2023072617371373700_bib12 article-title: Stem cell proliferation and quiescence--two sides of the same coin publication-title: PLOS Comput. Biol. doi: 10.1371/journal.pcbi.1000447 – volume: 211 start-page: 217 year: 2014 ident: 2023072617371373700_bib38 article-title: High c-Kit expression identifies hematopoietic stem cells with impaired self-renewal and megakaryocytic bias publication-title: J. Exp. Med. doi: 10.1084/jem.20131128 – volume: 100 start-page: 4410 year: 2002 ident: 2023072617371373700_bib33 article-title: Transgenic targeting with regulatory elements of the human CD34 gene publication-title: Blood. doi: 10.1182/blood-2002-02-0355 – volume: 16 start-page: 712 year: 2015 ident: 2023072617371373700_bib48 article-title: Combined Single-Cell Functional and Gene Expression Analysis Resolves Heterogeneity within Stem Cell Populations publication-title: Cell Stem Cell. doi: 10.1016/j.stem.2015.04.004 – volume: 44 start-page: 23 year: 2006 ident: 2023072617371373700_bib2 article-title: Efficient method to generate single-copy transgenic mice by site-specific integration in embryonic stem cells publication-title: Genesis. doi: 10.1002/gene.20180 – volume: 26 start-page: 873 year: 2010 ident: 2023072617371373700_bib49 article-title: Fast and SNP-tolerant detection of complex variants and splicing in short reads publication-title: Bioinformatics. doi: 10.1093/bioinformatics/btq057 – volume: 16 start-page: 178 year: 2015 ident: 2023072617371373700_bib45 article-title: Histone exchange, chromatin structure and the regulation of transcription publication-title: Nat. Rev. Mol. Cell Biol. doi: 10.1038/nrm3941 – volume: 135 start-page: 1118 year: 2008 ident: 2023072617371373700_bib47 article-title: Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair publication-title: Cell. doi: 10.1016/j.cell.2008.10.048 – volume: 4 year: 2009 ident: 2023072617371373700_bib44 article-title: Estimating dormant and active hematopoietic stem cell kinetics through extensive modeling of bromodeoxyuridine label-retaining cell dynamics publication-title: PLoS One. doi: 10.1371/journal.pone.0006972 – volume: 34 start-page: 449 year: 2016 ident: 2023072617371373700_bib16 article-title: Fate Mapping and Quantitation of Hematopoiesis In Vivo publication-title: Annu. Rev. Immunol. doi: 10.1146/annurev-immunol-032414-112019 – volume: 30 start-page: 923 year: 2014 ident: 2023072617371373700_bib25 article-title: featureCounts: an efficient general purpose program for assigning sequence reads to genomic features publication-title: Bioinformatics. doi: 10.1093/bioinformatics/btt656 – volume: 518 start-page: 542 year: 2015 ident: 2023072617371373700_bib6 article-title: Fundamental properties of unperturbed haematopoiesis from stem cells in vivo publication-title: Nature. doi: 10.1038/nature14242 – volume: 25 start-page: 345 year: 2007 ident: 2023072617371373700_bib18 article-title: Continuous histone H2B and transcription-dependent histone H3 exchange in yeast cells outside of replication publication-title: Mol. Cell. doi: 10.1016/j.molcel.2007.01.019
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Snippet	The proliferative activity of aging hematopoietic stem cells (HSCs) is controversially discussed. Inducible fluorescent histone 2B fusion protein (H2B-FP)... Morcos et al. show that there is no evidence for abrupt entry of aging hematopoietic stem cells into quiescence after four divisions as previously suggested....
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SubjectTerms	Aging - physiology Animals cd34 Clinical Medicine dynamics exchange Fluorescence Gene Expression Regulation gene-expression Hematologi Hematology Hematopoiesis Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - metabolism heterogeneity Histones - metabolism history Immunologi inom det medicinska området Immunology Immunology in the Medical Area Kinetics Klinisk medicin Medical and Health Sciences Medicin och hälsovetenskap Mice, Inbred C57BL Mitosis Models, Biological proliferation Proteolysis Recombinant Fusion Proteins - metabolism Research & Experimental Medicine self-renewal Stem Cells & Regeneration
Title	Continuous mitotic activity of primitive hematopoietic stem cells in adult mice
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