Transcriptional Control of Gene Expression and the Heterogeneous Cellular Identity of Erythroblastic Island Macrophages

During definitive erythropoiesis, maturation of erythroid progenitors into enucleated reticulocytes requires the erythroblastic island (EBI) niche comprising a central macrophage attached to differentiating erythroid progenitors. Normally, the macrophage provides a nurturing environment for maturati...

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Autores principales: Kaustav Mukherjee, James J. Bieker
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:1b9afa530f5b42edb1bced44db6697bd2021-11-22T07:05:04ZTranscriptional Control of Gene Expression and the Heterogeneous Cellular Identity of Erythroblastic Island Macrophages1664-802110.3389/fgene.2021.756028https://doaj.org/article/1b9afa530f5b42edb1bced44db6697bd2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.756028/fullhttps://doaj.org/toc/1664-8021During definitive erythropoiesis, maturation of erythroid progenitors into enucleated reticulocytes requires the erythroblastic island (EBI) niche comprising a central macrophage attached to differentiating erythroid progenitors. Normally, the macrophage provides a nurturing environment for maturation of erythroid cells. Its critical physiologic importance entails aiding in recovery from anemic insults, such as systemic stress or acquired disease. Considerable interest in characterizing the central macrophage of the island niche led to the identification of putative cell surface markers enriched in island macrophages, enabling isolation and characterization. Recent studies focus on bulk and single cell transcriptomics of the island macrophage during adult steady-state erythropoiesis and embryonic erythropoiesis. They reveal that the island macrophage is a distinct cell type but with widespread cellular heterogeneity, likely suggesting distinct developmental origins and biological function. These studies have also uncovered transcriptional programs that drive gene expression in the island macrophage. Strikingly, the master erythroid regulator EKLF/Klf1 seems to also play a major role in specifying gene expression in island macrophages, including a putative EKLF/Klf1-dependent transcription circuit. Our present review and analysis of mouse single cell genetic patterns suggest novel expression characteristics that will enable a clear enrichment of EBI subtypes and resolution of island macrophage heterogeneity. Specifically, the discovery of markers such as Epor, and specific features for EKLF/Klf1-expressing island macrophages such as Sptb and Add2, or for SpiC-expressing island macrophage such as Timd4, or for Maf/Nr1h3-expressing island macrophage such as Vcam1, opens exciting possibilities for further characterization of these unique macrophage cell types in the context of their critical developmental function.Kaustav MukherjeeKaustav MukherjeeJames J. BiekerJames J. BiekerJames J. BiekerJames J. BiekerFrontiers Media S.A.articleerythroblastic islandmammalian hematopoiesismacrophage identityerythropoiesistranscriptional controlsingle cell analysesGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic erythroblastic island
mammalian hematopoiesis
macrophage identity
erythropoiesis
transcriptional control
single cell analyses
Genetics
QH426-470
spellingShingle erythroblastic island
mammalian hematopoiesis
macrophage identity
erythropoiesis
transcriptional control
single cell analyses
Genetics
QH426-470
Kaustav Mukherjee
Kaustav Mukherjee
James J. Bieker
James J. Bieker
James J. Bieker
James J. Bieker
Transcriptional Control of Gene Expression and the Heterogeneous Cellular Identity of Erythroblastic Island Macrophages
description During definitive erythropoiesis, maturation of erythroid progenitors into enucleated reticulocytes requires the erythroblastic island (EBI) niche comprising a central macrophage attached to differentiating erythroid progenitors. Normally, the macrophage provides a nurturing environment for maturation of erythroid cells. Its critical physiologic importance entails aiding in recovery from anemic insults, such as systemic stress or acquired disease. Considerable interest in characterizing the central macrophage of the island niche led to the identification of putative cell surface markers enriched in island macrophages, enabling isolation and characterization. Recent studies focus on bulk and single cell transcriptomics of the island macrophage during adult steady-state erythropoiesis and embryonic erythropoiesis. They reveal that the island macrophage is a distinct cell type but with widespread cellular heterogeneity, likely suggesting distinct developmental origins and biological function. These studies have also uncovered transcriptional programs that drive gene expression in the island macrophage. Strikingly, the master erythroid regulator EKLF/Klf1 seems to also play a major role in specifying gene expression in island macrophages, including a putative EKLF/Klf1-dependent transcription circuit. Our present review and analysis of mouse single cell genetic patterns suggest novel expression characteristics that will enable a clear enrichment of EBI subtypes and resolution of island macrophage heterogeneity. Specifically, the discovery of markers such as Epor, and specific features for EKLF/Klf1-expressing island macrophages such as Sptb and Add2, or for SpiC-expressing island macrophage such as Timd4, or for Maf/Nr1h3-expressing island macrophage such as Vcam1, opens exciting possibilities for further characterization of these unique macrophage cell types in the context of their critical developmental function.
format article
author Kaustav Mukherjee
Kaustav Mukherjee
James J. Bieker
James J. Bieker
James J. Bieker
James J. Bieker
author_facet Kaustav Mukherjee
Kaustav Mukherjee
James J. Bieker
James J. Bieker
James J. Bieker
James J. Bieker
author_sort Kaustav Mukherjee
title Transcriptional Control of Gene Expression and the Heterogeneous Cellular Identity of Erythroblastic Island Macrophages
title_short Transcriptional Control of Gene Expression and the Heterogeneous Cellular Identity of Erythroblastic Island Macrophages
title_full Transcriptional Control of Gene Expression and the Heterogeneous Cellular Identity of Erythroblastic Island Macrophages
title_fullStr Transcriptional Control of Gene Expression and the Heterogeneous Cellular Identity of Erythroblastic Island Macrophages
title_full_unstemmed Transcriptional Control of Gene Expression and the Heterogeneous Cellular Identity of Erythroblastic Island Macrophages
title_sort transcriptional control of gene expression and the heterogeneous cellular identity of erythroblastic island macrophages
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/1b9afa530f5b42edb1bced44db6697bd
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