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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Detalles Bibliográficos
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
Descripción
Sumario: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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