Lineage specification of human dendritic cell is marked by expression of the transcriptionl factor IRF8 in HSCs and MPPs

The origin and specification of human dendritic cells (DCs) have not been investigated at clonal level. Using clonal assays combined with statistical computation to quantify the yield of granulocytes, monocytes, lymphocytes and three subsets of DCs from single human CD34(+) progenitor cells, we show...

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Autores principales: Lee, Jaeyop, Zhou, Yu Jerry, Ma, Wenji, Zhang, Wanwei, Aljoufi, Arafat, Luh, Thomas, Lucero, Kimberly, Liang, Deguang, Thomsen, Matthew, Bhagat, Govind, Shen, Yufeng, Liu, Kang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743223/
https://www.ncbi.nlm.nih.gov/pubmed/28650480
http://dx.doi.org/10.1038/ni.3789
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author Lee, Jaeyop
Zhou, Yu Jerry
Ma, Wenji
Zhang, Wanwei
Aljoufi, Arafat
Luh, Thomas
Lucero, Kimberly
Liang, Deguang
Thomsen, Matthew
Bhagat, Govind
Shen, Yufeng
Liu, Kang
author_facet Lee, Jaeyop
Zhou, Yu Jerry
Ma, Wenji
Zhang, Wanwei
Aljoufi, Arafat
Luh, Thomas
Lucero, Kimberly
Liang, Deguang
Thomsen, Matthew
Bhagat, Govind
Shen, Yufeng
Liu, Kang
author_sort Lee, Jaeyop
collection PubMed
description The origin and specification of human dendritic cells (DCs) have not been investigated at clonal level. Using clonal assays combined with statistical computation to quantify the yield of granulocytes, monocytes, lymphocytes and three subsets of DCs from single human CD34(+) progenitor cells, we show DC lineage specification occurs in parallel with myeloid and lymphoid lineages in HSCs, starting as a lineage bias defined by specific transcriptional programs correlated with the relative IRF8/PU.1 ratios, which is transmitted to most progeny and reinforced by FLT3L-driven IRF8 upregulation over division. We propose a model in which DC lineage specification is driven by parallel and inheritable transcriptional programs in HSCs, and reinforced over cell division by recursive interaction between transcriptional programs and extrinsic signals.
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spelling pubmed-57432232017-12-27 Lineage specification of human dendritic cell is marked by expression of the transcriptionl factor IRF8 in HSCs and MPPs Lee, Jaeyop Zhou, Yu Jerry Ma, Wenji Zhang, Wanwei Aljoufi, Arafat Luh, Thomas Lucero, Kimberly Liang, Deguang Thomsen, Matthew Bhagat, Govind Shen, Yufeng Liu, Kang Nat Immunol Article The origin and specification of human dendritic cells (DCs) have not been investigated at clonal level. Using clonal assays combined with statistical computation to quantify the yield of granulocytes, monocytes, lymphocytes and three subsets of DCs from single human CD34(+) progenitor cells, we show DC lineage specification occurs in parallel with myeloid and lymphoid lineages in HSCs, starting as a lineage bias defined by specific transcriptional programs correlated with the relative IRF8/PU.1 ratios, which is transmitted to most progeny and reinforced by FLT3L-driven IRF8 upregulation over division. We propose a model in which DC lineage specification is driven by parallel and inheritable transcriptional programs in HSCs, and reinforced over cell division by recursive interaction between transcriptional programs and extrinsic signals. 2017-06-26 2017-08 /pmc/articles/PMC5743223/ /pubmed/28650480 http://dx.doi.org/10.1038/ni.3789 Text en http://creativecommons.org/licenses/by/4.0/ Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Lee, Jaeyop
Zhou, Yu Jerry
Ma, Wenji
Zhang, Wanwei
Aljoufi, Arafat
Luh, Thomas
Lucero, Kimberly
Liang, Deguang
Thomsen, Matthew
Bhagat, Govind
Shen, Yufeng
Liu, Kang
Lineage specification of human dendritic cell is marked by expression of the transcriptionl factor IRF8 in HSCs and MPPs
title Lineage specification of human dendritic cell is marked by expression of the transcriptionl factor IRF8 in HSCs and MPPs
title_full Lineage specification of human dendritic cell is marked by expression of the transcriptionl factor IRF8 in HSCs and MPPs
title_fullStr Lineage specification of human dendritic cell is marked by expression of the transcriptionl factor IRF8 in HSCs and MPPs
title_full_unstemmed Lineage specification of human dendritic cell is marked by expression of the transcriptionl factor IRF8 in HSCs and MPPs
title_short Lineage specification of human dendritic cell is marked by expression of the transcriptionl factor IRF8 in HSCs and MPPs
title_sort lineage specification of human dendritic cell is marked by expression of the transcriptionl factor irf8 in hscs and mpps
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743223/
https://www.ncbi.nlm.nih.gov/pubmed/28650480
http://dx.doi.org/10.1038/ni.3789
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