Transcriptional heterogeneity and lineage commitment in myeloid progenitors
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ABSTRACT:
PROVIDER: PRJNA295198 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE34892: IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid progenitors (Affymetrix). GSE34915: IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid progenitors (Illumina). Refer to individual Series
2012-01-07 | E-GEOD-34917 | biostudies-arrayexpress
Project description:Within the bone marrow, hematopoietic stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with the in vivo potential or gene regulatory mechanisms. Here we comprehensively identify myeloid progenitor subpopulations by transcriptional sorting of single cells from the bone marrow. We describe multiple progenitor subgroups showing unexpected transcriptional priming towards seven differentiation fates, but no progenitors with a mixed state. Transcriptional differentiation is correlated with combinations of known and previously undefined transcription factors, suggesting the process is tightly regulated. Histone maps and knockout assays are consistent with the transcriptional states while traditional transplantation experiments are only partially overlapping myeloid transcriptional priming. Our analyses uncover the function of the underlying regulatory mechanisms for several sub groups and establishes a general framework for dissecting hematopoiesis. Bone marrow common myeloid progenitor H3K4me2 profiles were generated by deep sequencing of iChIP libraries on an Illumina NextSeq
2015-11-25 | E-GEOD-72858 | biostudies-arrayexpress
Project description:Epigenetic modifications must underlie lineage-specific differentiation since terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Hematopoiesis provides a well-defined model of progressive differentiation in which to study the role of epigenetic modifications in cell fate decisions. Multi-potent progenitors (MPPs) can differentiate into all blood cell lineages, while downstream progenitors commit to either myeloerythroid or lymphoid lineages. While DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs {Broske, 2009 #6}, a comprehensive DNA methylation map of hematopoietic progenitors, or of any cell lineage, does not exist. Here we have generated a mouse DNA methylation map, examining 4.6 million CpG sites throughout the genome including all CpG islands and shores, examining MPPs, all lymphoid progenitors (ALPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Interestingly, differentiation towards the myeloid lineage corresponds with a net decrease in DNA methylation, while lymphoid commitment involves a net increase in DNA methylation, but both show substantial dynamic changes consistent with epigenetic plasticity during development. By comparing lineage-specific DNA methylation to gene expression array data, we find many examples of genes and pathways not previously known to be involved in lymphoid/myeloid differentiation, such as Gcnt2, Arl4c, Gadd45α, and Jdp2. Several transcription factors, including Meis1 and Prdm16 were methylated and silenced during differentiation, suggesting a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome appears to be important in hematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation, often correlating with gene expression changes, and define a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions. mRNA expression of 8 hematopoietic progenitor populations [MPPFL-(5), MPPFL+(3), CMP(3), GMP(3), CLP(3), DN1(3), DN2(3), DN3(3)] were compared
2010-08-15 | E-GEOD-20244 | biostudies-arrayexpress
Project description:Within the bone marrow, hematopoietic stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with the in vivo potential or gene regulatory mechanisms. Here we comprehensively identify myeloid progenitor subpopulations by transcriptional sorting of single cells from the bone marrow. We describe multiple progenitor subgroups showing unexpected transcriptional priming towards seven differentiation fates, but no progenitors with a mixed state. Transcriptional differentiation is correlated with combinations of known and previously undefined transcription factors, suggesting the process is tightly regulated. Histone maps and knockout assays are consistent with the transcriptional states while traditional transplantation experiments are only partially overlapping myeloid transcriptional priming. Our analyses uncover the function of the underlying regulatory mechanisms for several sub groups and establishes a general framework for dissecting hematopoiesis. Bone marrow Lin- cKit+ Sca1- myeloid progenitors mRNA profiles from single cells were generated by deep sequencing of thousands of single cells, sequenced in several batches in an Illumina NextSeq Please note that [1] raw data files were processed as single-ended file since second read (mate) files contain only cell/molecule barcodes and therefore, not provided. This information was appended to the fastq entry header [2] The 'experimental_design.txt' file explains the correspondence of each single cell (WXXXX) in the 'umitab.txt' to a sample (ABXXXX).
2015-11-25 | E-GEOD-72857 | biostudies-arrayexpress
Project description:Within the bone marrow, hematopoietic stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with the in vivo potential or gene regulatory mechanisms. Here we comprehensively identify myeloid progenitor subpopulations by transcriptional sorting of single cells from the bone marrow. We describe multiple progenitor subgroups showing unexpected transcriptional priming towards seven differentiation fates, but no progenitors with a mixed state. Transcriptional differentiation is correlated with combinations of known and previously undefined transcription factors, suggesting the process is tightly regulated. Histone maps and knockout assays are consistent with the transcriptional states while traditional transplantation experiments are only partially overlapping myeloid transcriptional priming. Our analyses uncover the function of the underlying regulatory mechanisms for several sub groups and establishes a general framework for dissecting hematopoiesis.
2015-11-25 | GSE72858 | GEO
Project description:Epigenetic modifications must underlie lineage-specific differentiation since terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Hematopoiesis provides a well-defined model of progressive differentiation in which to study the role of epigenetic modifications in cell fate decisions. Multi-potent progenitors (MPPs) can differentiate into all blood cell lineages, while downstream progenitors commit to either myeloerythroid or lymphoid lineages. While DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs {Broske, 2009 #6}, a comprehensive DNA methylation map of hematopoietic progenitors, or of any cell lineage, does not exist. Here we have generated a mouse DNA methylation map, examining 4.6 million CpG sites throughout the genome including all CpG islands and shores, examining MPPs, all lymphoid progenitors (ALPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Interestingly, differentiation towards the myeloid lineage corresponds with a net decrease in DNA methylation, while lymphoid commitment involves a net increase in DNA methylation, but both show substantial dynamic changes consistent with epigenetic plasticity during development. By comparing lineage-specific DNA methylation to gene expression array data, we find many examples of genes and pathways not previously known to be involved in lymphoid/myeloid differentiation, such as Gcnt2, Arl4c, Gadd45α, and Jdp2. Several transcription factors, including Meis1 and Prdm16 were methylated and silenced during differentiation, suggesting a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome appears to be important in hematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation, often correlating with gene expression changes, and define a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions.
2010-08-15 | GSE20244 | GEO
Project description:Understanding how cellular function is imprinted during development requires the identification of factors controlling lineage specification and commitment, and the intermediate progenitors in which they act. Using population level and single cell approaches, we examine transcriptional and functional heterogeneity within early innate lymphoid cells (ILC) progenitors. We identify a developmental bifurcation toward dendritic cell fate that reveals the uncommitted state of early specified ILC progenitors. We subsequently characterize an ILC-commitment checkpoint controlled by the transcription factor TCF-1. The present study reveals unexpected heterogeneity within early innate progenitor populations, and characterizes lineage infidelity that accompanies early ILC specification prior to commitment.
2019-04-22 | GSE113765 | GEO
Project description:Within the bone marrow, hematopoietic stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with the in vivo potential or gene regulatory mechanisms. Here we comprehensively identify myeloid progenitor subpopulations by transcriptional sorting of single cells from the bone marrow. We describe multiple progenitor subgroups showing unexpected transcriptional priming towards seven differentiation fates, but no progenitors with a mixed state. Transcriptional differentiation is correlated with combinations of known and previously undefined transcription factors, suggesting the process is tightly regulated. Histone maps and knockout assays are consistent with the transcriptional states while traditional transplantation experiments are only partially overlapping myeloid transcriptional priming. Our analyses uncover the function of the underlying regulatory mechanisms for several sub groups and establishes a general framework for dissecting hematopoiesis.
2015-11-25 | GSE72857 | GEO
Project description:Understanding how cellular function is imprinted during development requires the identification of factors controlling lineage specification and commitment, and the intermediate progenitors in which they act. Using population level and single cell approaches, we examine transcriptional and functional heterogeneity within early innate lymphoid cells (ILC) progenitors. We identify a developmental bifurcation toward dendritic cell fate that reveals the uncommitted state of early specified ILC progenitors. We subsequently characterize an ILC-commitment checkpoint controlled by the transcription factor TCF-1. The present study reveals unexpected heterogeneity within early innate progenitor populations, and characterizes lineage infidelity that accompanies early ILC specification prior to commitment.
2019-04-22 | GSE113766 | GEO
Project description:While most blood lineages are assumed to mature through a single cellular and developmental route downstream of hematopoietic stem cells (HSCs), dendritic cells (DCs) can be derived from both myeloid and lymphoid progenitors in vivo. To determine how distinct progenitors can generate similar downstream lineages, we examined the transcriptional changes that accompany loss of in vivo myeloid potential as common myeloid progenitors (CMPs) differentiate into common dendritic cell progenitors (CDPs), and as lymphoid-primed multipotent progenitors (LMPPs) differentiate into all lymphoid progenitors (ALPs). Microarray studies revealed that Interferon regulatory factor 8 (IRF-8) expression increased during each of these transitions. Competitive reconstitutions using Irf8-/- bone marrow demonstrated cell-intrinsic defects in the formation of CDPs and all splenic dendritic cell subsets. Irf8-/- CMPs and, unexpectedly, Irf8-/- ALPs produced more neutrophils in vivo than their wild type counterparts at the expense of DCs. Retroviral expression of IRF-8 in multiple progenitors led to reduced neutrophil production and increased numbers of DCs, even in the granulocyte-macrophage progenitor (GMP), which does not normally possess conventional DC potential. These data suggest that IRF-8 represses a neutrophil module of development and promotes convergent DC development from multiple lymphoid and myeloid progenitors autonomously of cellular context. CMP (Lineage-c-kithiSca-1-CD11c- CD34+ Flk2+CD16/32-CD115- ) or CDP (Lin-c-kitintSca-1-CD34+Flk2+CD16/32-CD115+) were double sorted from the bone marrow of wild type C57BL/6 mice. RNA was extracted from 10,000-30,000 sorted cells using Trizol (Invitrogen) and linear acrylamide (Ambion), amplified using Affymetrix Two-Cycle Amplification and IVT kits (Affymetrix), and hybridized to Affymetrix Mouse Genome 430 2.0 chips.
2012-01-07 | E-GEOD-34892 | biostudies-arrayexpress