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Aging alters the epigenetic asymmetry of HSC division
by
Glauche, Ingmar
, Sacma, Mehmet
, Vollmer, Angelika
, Zheng, Yi
, Cabezas-Wallscheid, Nina
, Knudson, Luke
, Nattamai, Kalpana J.
, Sakk, Vadim
, Marka, Gina
, Klose, Markus
, Florian, M. Carolina
, Mulaw, Medhanie A.
, Geiger, Hartmut
, Jablanovic, Jelena
, Soller, Karin
in
Aging
/ Aging - metabolism
/ Animals
/ Asymmetric Cell Division - genetics
/ Biology and Life Sciences
/ Bone Marrow Cells - cytology
/ Bone Marrow Cells - metabolism
/ cdc42 GTP-Binding Protein - metabolism
/ Cell Aggregation
/ Cell division
/ Cell Division - genetics
/ Cell Lineage - drug effects
/ Cell Polarity - drug effects
/ Cellular Senescence - genetics
/ Chromatin
/ Epigenesis, Genetic
/ Epigenetic inheritance
/ Genetic aspects
/ Hematopoietic stem cells
/ Hematopoietic Stem Cells - cytology
/ Hematopoietic Stem Cells - metabolism
/ Medicine and Health Sciences
/ Mice, Inbred C57BL
/ Observations
/ Research and Analysis Methods
/ Transcriptome - genetics
/ Wnt-5a Protein - pharmacology
2018
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Aging alters the epigenetic asymmetry of HSC division
by
Glauche, Ingmar
, Sacma, Mehmet
, Vollmer, Angelika
, Zheng, Yi
, Cabezas-Wallscheid, Nina
, Knudson, Luke
, Nattamai, Kalpana J.
, Sakk, Vadim
, Marka, Gina
, Klose, Markus
, Florian, M. Carolina
, Mulaw, Medhanie A.
, Geiger, Hartmut
, Jablanovic, Jelena
, Soller, Karin
in
Aging
/ Aging - metabolism
/ Animals
/ Asymmetric Cell Division - genetics
/ Biology and Life Sciences
/ Bone Marrow Cells - cytology
/ Bone Marrow Cells - metabolism
/ cdc42 GTP-Binding Protein - metabolism
/ Cell Aggregation
/ Cell division
/ Cell Division - genetics
/ Cell Lineage - drug effects
/ Cell Polarity - drug effects
/ Cellular Senescence - genetics
/ Chromatin
/ Epigenesis, Genetic
/ Epigenetic inheritance
/ Genetic aspects
/ Hematopoietic stem cells
/ Hematopoietic Stem Cells - cytology
/ Hematopoietic Stem Cells - metabolism
/ Medicine and Health Sciences
/ Mice, Inbred C57BL
/ Observations
/ Research and Analysis Methods
/ Transcriptome - genetics
/ Wnt-5a Protein - pharmacology
2018
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Aging alters the epigenetic asymmetry of HSC division
by
Glauche, Ingmar
, Sacma, Mehmet
, Vollmer, Angelika
, Zheng, Yi
, Cabezas-Wallscheid, Nina
, Knudson, Luke
, Nattamai, Kalpana J.
, Sakk, Vadim
, Marka, Gina
, Klose, Markus
, Florian, M. Carolina
, Mulaw, Medhanie A.
, Geiger, Hartmut
, Jablanovic, Jelena
, Soller, Karin
in
Aging
/ Aging - metabolism
/ Animals
/ Asymmetric Cell Division - genetics
/ Biology and Life Sciences
/ Bone Marrow Cells - cytology
/ Bone Marrow Cells - metabolism
/ cdc42 GTP-Binding Protein - metabolism
/ Cell Aggregation
/ Cell division
/ Cell Division - genetics
/ Cell Lineage - drug effects
/ Cell Polarity - drug effects
/ Cellular Senescence - genetics
/ Chromatin
/ Epigenesis, Genetic
/ Epigenetic inheritance
/ Genetic aspects
/ Hematopoietic stem cells
/ Hematopoietic Stem Cells - cytology
/ Hematopoietic Stem Cells - metabolism
/ Medicine and Health Sciences
/ Mice, Inbred C57BL
/ Observations
/ Research and Analysis Methods
/ Transcriptome - genetics
/ Wnt-5a Protein - pharmacology
2018
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Journal Article
Aging alters the epigenetic asymmetry of HSC division
2018
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Overview
Hematopoietic stem cells (HSCs) balance self-renewal and differentiation to maintain homeostasis. With aging, the frequency of polar HSCs decreases. Cell polarity in HSCs is controlled by the activity of the small RhoGTPase cell division control protein 42 (Cdc42). Here we demonstrate-using a comprehensive set of paired daughter cell analyses that include single-cell 3D confocal imaging, single-cell transplants, single-cell RNA-seq, and single-cell transposase-accessible chromatin sequencing (ATAC-seq)-that the outcome of HSC divisions is strongly linked to the polarity status before mitosis, which is in turn determined by the level of the activity Cdc42 in stem cells. Aged apolar HSCs undergo preferentially self-renewing symmetric divisions, resulting in daughter stem cells with reduced regenerative capacity and lymphoid potential, while young polar HSCs undergo preferentially asymmetric divisions. Mathematical modeling in combination with experimental data implies a mechanistic role of the asymmetric sorting of Cdc42 in determining the potential of daughter cells via epigenetic mechanisms. Therefore, molecules that control HSC polarity might serve as modulators of the mode of stem cell division regulating the potential of daughter cells.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Animals
/ Asymmetric Cell Division - genetics
/ Bone Marrow Cells - cytology
/ Bone Marrow Cells - metabolism
/ cdc42 GTP-Binding Protein - metabolism
/ Cell Polarity - drug effects
/ Cellular Senescence - genetics
/ Hematopoietic Stem Cells - cytology
/ Hematopoietic Stem Cells - metabolism
/ Medicine and Health Sciences
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