Cargando…

Single cell transcriptomics reveals unanticipated features of early hematopoietic precursors

Molecular changes underlying stem cell differentiation are of fundamental interest. scRNA-seq on murine hematopoietic stem cells (HSC) and their progeny MPP1 separated the cells into 3 main clusters with distinct features: active, quiescent, and an un-characterized cluster. Induction of anemia resul...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Jennifer, Tanaka, Yoshiaki, Seay, Montrell, Li, Zhen, Jin, Jiaqi, Garmire, Lana Xia, Zhu, Xun, Taylor, Ashley, Li, Weidong, Euskirchen, Ghia, Halene, Stephanie, Kluger, Yuval, Snyder, Michael P., Park, In-Hyun, Pan, Xinghua, Weissman, Sherman Morton
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388401/
https://www.ncbi.nlm.nih.gov/pubmed/28003475
http://dx.doi.org/10.1093/nar/gkw1214
_version_ 1782521123521429504
author Yang, Jennifer
Tanaka, Yoshiaki
Seay, Montrell
Li, Zhen
Jin, Jiaqi
Garmire, Lana Xia
Zhu, Xun
Taylor, Ashley
Li, Weidong
Euskirchen, Ghia
Halene, Stephanie
Kluger, Yuval
Snyder, Michael P.
Park, In-Hyun
Pan, Xinghua
Weissman, Sherman Morton
author_facet Yang, Jennifer
Tanaka, Yoshiaki
Seay, Montrell
Li, Zhen
Jin, Jiaqi
Garmire, Lana Xia
Zhu, Xun
Taylor, Ashley
Li, Weidong
Euskirchen, Ghia
Halene, Stephanie
Kluger, Yuval
Snyder, Michael P.
Park, In-Hyun
Pan, Xinghua
Weissman, Sherman Morton
author_sort Yang, Jennifer
collection PubMed
description Molecular changes underlying stem cell differentiation are of fundamental interest. scRNA-seq on murine hematopoietic stem cells (HSC) and their progeny MPP1 separated the cells into 3 main clusters with distinct features: active, quiescent, and an un-characterized cluster. Induction of anemia resulted in mobilization of the quiescent to the active cluster and of the early to later stage of cell cycle, with marked increase in expression of certain transcription factors (TFs) while maintaining expression of interferon response genes. Cells with surface markers of long term HSC increased the expression of a group of TFs expressed highly in normal cycling MPP1 cells. However, at least Id1 and Hes1 were significantly activated in both HSC and MPP1 cells in anemic mice. Lineage-specific genes were differently expressed between cells, and correlated with the cell cycle stages with a specific augmentation of erythroid related genes in the G2/M phase. Most lineage specific TFs were stochastically expressed in the early precursor cells, but a few, such as Klf1, were detected only at very low levels in few precursor cells. The activation of these factors may correlate with stages of differentiation. This study reveals effects of cell cycle progression on the expression of lineage specific genes in precursor cells, and suggests that hematopoietic stress changes the balance of renewal and differentiation in these homeostatic cells.
format Online
Article
Text
id pubmed-5388401
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-53884012017-04-18 Single cell transcriptomics reveals unanticipated features of early hematopoietic precursors Yang, Jennifer Tanaka, Yoshiaki Seay, Montrell Li, Zhen Jin, Jiaqi Garmire, Lana Xia Zhu, Xun Taylor, Ashley Li, Weidong Euskirchen, Ghia Halene, Stephanie Kluger, Yuval Snyder, Michael P. Park, In-Hyun Pan, Xinghua Weissman, Sherman Morton Nucleic Acids Res Genomics Molecular changes underlying stem cell differentiation are of fundamental interest. scRNA-seq on murine hematopoietic stem cells (HSC) and their progeny MPP1 separated the cells into 3 main clusters with distinct features: active, quiescent, and an un-characterized cluster. Induction of anemia resulted in mobilization of the quiescent to the active cluster and of the early to later stage of cell cycle, with marked increase in expression of certain transcription factors (TFs) while maintaining expression of interferon response genes. Cells with surface markers of long term HSC increased the expression of a group of TFs expressed highly in normal cycling MPP1 cells. However, at least Id1 and Hes1 were significantly activated in both HSC and MPP1 cells in anemic mice. Lineage-specific genes were differently expressed between cells, and correlated with the cell cycle stages with a specific augmentation of erythroid related genes in the G2/M phase. Most lineage specific TFs were stochastically expressed in the early precursor cells, but a few, such as Klf1, were detected only at very low levels in few precursor cells. The activation of these factors may correlate with stages of differentiation. This study reveals effects of cell cycle progression on the expression of lineage specific genes in precursor cells, and suggests that hematopoietic stress changes the balance of renewal and differentiation in these homeostatic cells. Oxford University Press 2017-02-17 2016-12-20 /pmc/articles/PMC5388401/ /pubmed/28003475 http://dx.doi.org/10.1093/nar/gkw1214 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Genomics
Yang, Jennifer
Tanaka, Yoshiaki
Seay, Montrell
Li, Zhen
Jin, Jiaqi
Garmire, Lana Xia
Zhu, Xun
Taylor, Ashley
Li, Weidong
Euskirchen, Ghia
Halene, Stephanie
Kluger, Yuval
Snyder, Michael P.
Park, In-Hyun
Pan, Xinghua
Weissman, Sherman Morton
Single cell transcriptomics reveals unanticipated features of early hematopoietic precursors
title Single cell transcriptomics reveals unanticipated features of early hematopoietic precursors
title_full Single cell transcriptomics reveals unanticipated features of early hematopoietic precursors
title_fullStr Single cell transcriptomics reveals unanticipated features of early hematopoietic precursors
title_full_unstemmed Single cell transcriptomics reveals unanticipated features of early hematopoietic precursors
title_short Single cell transcriptomics reveals unanticipated features of early hematopoietic precursors
title_sort single cell transcriptomics reveals unanticipated features of early hematopoietic precursors
topic Genomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388401/
https://www.ncbi.nlm.nih.gov/pubmed/28003475
http://dx.doi.org/10.1093/nar/gkw1214
work_keys_str_mv AT yangjennifer singlecelltranscriptomicsrevealsunanticipatedfeaturesofearlyhematopoieticprecursors
AT tanakayoshiaki singlecelltranscriptomicsrevealsunanticipatedfeaturesofearlyhematopoieticprecursors
AT seaymontrell singlecelltranscriptomicsrevealsunanticipatedfeaturesofearlyhematopoieticprecursors
AT lizhen singlecelltranscriptomicsrevealsunanticipatedfeaturesofearlyhematopoieticprecursors
AT jinjiaqi singlecelltranscriptomicsrevealsunanticipatedfeaturesofearlyhematopoieticprecursors
AT garmirelanaxia singlecelltranscriptomicsrevealsunanticipatedfeaturesofearlyhematopoieticprecursors
AT zhuxun singlecelltranscriptomicsrevealsunanticipatedfeaturesofearlyhematopoieticprecursors
AT taylorashley singlecelltranscriptomicsrevealsunanticipatedfeaturesofearlyhematopoieticprecursors
AT liweidong singlecelltranscriptomicsrevealsunanticipatedfeaturesofearlyhematopoieticprecursors
AT euskirchenghia singlecelltranscriptomicsrevealsunanticipatedfeaturesofearlyhematopoieticprecursors
AT halenestephanie singlecelltranscriptomicsrevealsunanticipatedfeaturesofearlyhematopoieticprecursors
AT klugeryuval singlecelltranscriptomicsrevealsunanticipatedfeaturesofearlyhematopoieticprecursors
AT snydermichaelp singlecelltranscriptomicsrevealsunanticipatedfeaturesofearlyhematopoieticprecursors
AT parkinhyun singlecelltranscriptomicsrevealsunanticipatedfeaturesofearlyhematopoieticprecursors
AT panxinghua singlecelltranscriptomicsrevealsunanticipatedfeaturesofearlyhematopoieticprecursors
AT weissmanshermanmorton singlecelltranscriptomicsrevealsunanticipatedfeaturesofearlyhematopoieticprecursors