Identification of the Common Origins of Osteoclasts, Macrophages, and Dendritic Cells in Human Hematopoiesis

Osteoclasts (OCs) originate from the myeloid cell lineage, but the successive steps in their lineage commitment are ill-defined, especially in humans. To clarify OC origin, we sorted cell populations from pediatric bone marrow (BM) by flow cytometry and assessed their differentiation potential in vi...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Stem cell reports Ročník 4; číslo 6; s. 984 - 994
Hlavní autoři: Xiao, Yanling, Zijl, Sebastiaan, Wang, Liqin, de Groot, Daniel C., van Tol, Maarten J., Lankester, Arjan C., Borst, Jannie
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Elsevier Inc 09.06.2015
Elsevier
Témata:
Antigens, CD34 - metabolism
Base Sequence
Bone Marrow Cells - cytology
Bone Marrow Cells - metabolism
CD11b Antigen - metabolism
Cell Differentiation
Cell Lineage
Dendritic Cells - cytology
Dendritic Cells - metabolism
fms-Like Tyrosine Kinase 3 - metabolism
Gene Expression Profiling
Hematopoiesis
High-Throughput Nucleotide Sequencing
Humans
Interleukin-3 Receptor alpha Subunit - metabolism
Macrophages - cytology
Macrophages - metabolism
Molecular Sequence Data
Osteoclasts - cytology
Osteoclasts - metabolism
Proto-Oncogene Proteins c-kit - metabolism
RNA, Messenger - chemistry
RNA, Messenger - metabolism
Sequence Analysis, DNA
Transcriptome
ISSN:2213-6711, 2213-6711
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí:Osteoclasts (OCs) originate from the myeloid cell lineage, but the successive steps in their lineage commitment are ill-defined, especially in humans. To clarify OC origin, we sorted cell populations from pediatric bone marrow (BM) by flow cytometry and assessed their differentiation potential in vitro. Within the CD11b−CD34+c-KIT+ BM cell population, OC-differentiation potential was restricted to FLT3+ cells and enriched in an IL3 receptor (R)αhigh subset that constituted less than 0.5% of total BM. These IL3Rαhigh cells also generated macrophages (MΦs) and dendritic cells (DCs) but lacked granulocyte (GR)-differentiation potential, as demonstrated at the clonal level. The IL3Rαlow subset was re-defined as common progenitor of GR, MΦ, OC, and DC (GMODP) and gave rise to the IL3Rαhigh subset that was identified as common progenitor of MΦ, OC, and DC (MODP). Unbiased transcriptome analysis of CD11b−CD34+c-KIT+FLT3+ IL3Rαlow and IL3Rαhigh subsets corroborated our definitions of the GMODP and MODP and their developmental relationship. [Display omitted] •CD34+c-Kit+Flt3+ IL3Rαhigh phenotype identifies human MΦ/OC/DC progenitor (MODP)•CD34+c-Kit+Flt3+ IL3Rαlow phenotype identifies GMODP, oligopotent for GR/MΦ/OC/DC•CD34+c-Kit+Flt3+ IL3Rαlow GMODP is upstream of CD34+c-Kit+Flt3+ IL3Rαhigh MODP•Transcriptome analysis supports definition and relationship of GMODP and MODP In this article, Borst, Xiao, and colleagues identify two hierarchically related hematopoietic progenitors in the human bone marrow that can give rise to osteoclasts, the cells that can resorb bone and are involved in various diseases. They show that osteoclasts share their developmental origin with macrophages and dendritic cells that have important immune regulatory functions.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2213-6711
2213-6711
DOI:10.1016/j.stemcr.2015.04.012