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Differential usage of Zeb2 enhancer distinguishes adult and embryonic hematopoiesis

ABSTRACT: Differential usage of Zeb2 enhancer distinguishes adult and embryonic hematopoiesis

PROVIDER: PRJNA704321 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13786100_1.fastq.gz	Fastqsanger.gz
	SRR13786100_2.fastq.gz	Fastqsanger.gz
	SRR13786101_1.fastq.gz	Fastqsanger.gz
	SRR13786101_2.fastq.gz	Fastqsanger.gz
	SRR13769977_1.fastq.gz	Fastqsanger.gz

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Differential usage of Zeb2 enhancer distinguishes adult and embryonic hematopoiesis [scATAC-seq]

Project description:Differential usage of Zeb2 enhancer distinguishes adult and embryonic hematopoiesis [scATAC-seq]

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Differential usage of Zeb2 enhancer distinguishes adult and embryonic hematopoiesis [bulkATAC-seq]

Project description:Differential usage of Zeb2 enhancer distinguishes adult and embryonic hematopoiesis [bulkATAC-seq]

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Differential usage of Zeb2 enhancer distinguishes adult and embryonic hematopoiesis [bulkATAC-seq]

Project description:ATAC-seq of Zeb2 WT and Zeb2 enhancer KO B cells

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Differential usage of transcriptional repressor Zeb2 enhancers distinguishes adult and embryonic hematopoiesis.

Project description:The transcriptional repressor ZEB2 regulates development of many cell fates among somatic, neural, and hematopoietic lineages, but the basis for its requirement in these diverse lineages is unclear. Here, we identified a 400-basepair (bp) region located 165 kilobases (kb) upstream of the Zeb2 transcriptional start site (TSS) that binds the E proteins at several E-box motifs and was active in hematopoietic lineages. Germline deletion of this 400-bp region (Zeb2Δ-165mice) specifically prevented Zeb2 expression in hematopoietic stem cell (HSC)-derived lineages. Zeb2Δ-165 mice lacked development of plasmacytoid dendritic cells (pDCs), monocytes, and B cells. All macrophages in Zeb2Δ-165 mice were exclusively of embryonic origin. Using single-cell chromatin profiling, we identified a second Zeb2 enhancer located at +164-kb that was selectively active in embryonically derived lineages, but not HSC-derived ones. Thus, Zeb2 expression in adult, but not embryonic, hematopoiesis is selectively controlled by the -165-kb Zeb2 enhancer.

| S-EPMC8282756 | biostudies-literature

cMaf supports Zeb2 expression for primitive hematopoiesis (CUT&RUN)

Project description:Microglia arise exclusively from yolk sac (YS) progenitors during primitive hematopoiesis, while other tissue resident macrophages (TRMs)originate during transient-definitive and definitive hematopoiesis. Macrophages require the transcriptional repressor Zeb2 for development, and macrophages developing during definitive hematopoiesis require the ‒165 kb Zeb2 enhancer. However, microglia develop normally in Zeb2 ‒165kb mice lacking this enhancer, indicating that a distinct genetic program supports macrophage development in primitive hematopoiesis. Here, we identify the molecular basis that distinguishes macrophage development in primitive vs. definitive hematopoiesis. We show that all tissue resident macrophages (TRMs) that develop in Zeb2 ‒165kb mice arise exclusively during primitive hematopoiesis, showing that even erythro-myeloid progenitors (EMPs) from the transient-definitive stage rely on the ‒165 Zeb2 enhancer. Next, we identified the transcription factors Maf and Jun as being expressed by yolk sac (YS) progenitors during primitive hematopoiesis, but not by progenitors during definitive hematopoiesis. Further, we find that Maf and Jun together induce Zeb2 expression independently of the ‒165 kb Zeb2 enhancer and restore macrophage development from adult bone marrow progenitors in Zeb2 ‒165kb mice. Finally, Maf-deficient embryos show severe ablation of microglia development, confirming the in vivo requirement for Maf in supporting Zeb2 during primitive hematopoiesis. These results illustrate distinct transcriptional pathways controlling macrophage development during primitive and subsequent waves of hematopoiesis.

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Differential usage of Zeb2 enhancer distinguishes adult and embryonic hematopoiesis

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-06-12 | GSE167330 | GEO

Differential usage of Zeb2 enhancer distinguishes adult and embryonic hematopoiesis [scATAC-seq]

Project description:scATAC-seq of myeloid cells

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cMaf supports Zeb2 expression for primitive hematopoiesis (Multiome)

Project description:Tissue-resident macrophages (TRMs) are essential for tissue homeostasis and play a key role in disease and pathology. They originate from distinct waves of hematopoietic progenitors, including primitive, transient-definitive, and definitive hematopoiesis. We found that loss of the Zeb2 ‒165kb enhancer impairs monocyte development and alters TRM transcriptional landscapes, with only HSC-derived monocytes requiring Zeb2 for their development. In Zeb2∆‒165kb mice, primitive TRMs persist in tissues due to the lack of replacement by later hematopoietic waves, and Maf is required for maintaining Zeb2 expression in primitive macrophages.

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