CMaf supports Zeb2 expression for primitive hematopoiesis (FL mono RNA-seq)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE284309 | GEO | 2025/12/26
REPOSITORIES: GEO
Similar Datasets
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.
2025-12-26 | GSE283596 | GEO
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.
2025-12-26 | GSE283975 | GEO
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.
2025-12-26 | GSE304528 | GEO
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 linages is unclear. Our recent study uncovered a mutually repressive regulatory circuit between Id2 and Zeb2, and predicted that Zeb2 should be positively regulated by members of the E protein family of transcription factors. Here, we identified a 400bp enhancer region located 165 kilobases (kb) upstream of the Zeb2 transcriptional start site (TSS) that binds the E proteins E2A and E2-2 at several E-box motifs and is active in hematopoietic lineages. Germline deletion of this 400bp region (Zeb2 –165–/– mice) specifically prevented Zeb2 expression in hematopoietic stem cell (HSC) derived lineages. Zeb2 –165–/– mice lacked development of pDCs, monocytes, and B cells. Surprisingly, all macrophages in Zeb2 –165–/– mice were exclusively of embryonic origin. Using single-cell chromatin profiling, we identified a second Zeb2 enhancer located at +164kb that is selectively active in embryonically derived lineages, but not in lineages derived from HSCs. Thus, Zeb2 expression in adult, but not embryonic, hematopoiesis is selectively controlled by the –165kb Zeb2 enhancer.
2021-11-10 | GSE171564 | GEO
Project description:infarct size and subsequent deterioration in function. The identification of factors that enhance cardiac repair by the restoration of the vascular network is, therefore, of great significance. Here, we show that the transcription factor Zinc finger E-box-binding homeobox 2 (ZEB2) is increased in stressed cardiomyocytes and induces a cardioprotective cross-talk between cardiomyocytes and endothelial cells to enhance angiogenesis after ischemia. Single-cell sequencing indicates ZEB2 to be enriched in injured cardiomyocytes. Cardiomyocyte-specific deletion of ZEB2 results in impaired cardiac contractility and infarct healing post-myocardial infarction (post-MI), while cardiomyocyte-specific ZEB2 overexpression improves cardiomyocyte survival and cardiac function. We identified Thymosin 4 (TMSB4) and Prothymosin (PTMA) as main paracrine factors released from cardiomyocytes to stimulate angiogenesis by enhancing endothelial cell migration, and whose regulation is validated in our in vivo models. Therapeutic delivery of ZEB2 to cardiomyocytes in the infarcted heart induces the expression of TMSB4 and PTMA, which enhances angiogenesis and prevents cardiac dysfunction. These findings reveal ZEB2 as a beneficial factor during ischemic injury, which may hold promise for the identification of new therapies.
2021-03-23 | PXD022212 | Pride
Project description:The emergence of the hematopoietic system occurs in temporal waves across different tissues during mouse development. During these waves, the endothelial niche serves as a source of hematopoietic cells and provides molecular cues that potentially shape the tissue-specific lineage output. Although the endothelial-to-hematopoietic transition in the aorta-gonad-mesonephros is well understood, a systematic analysis of hematopoietic progenitors and their endothelial niche across fetal tissues is lacking. Here, we leverage single-cell RNA-sequencing of micro-dissected fetal tissues during their peak of hematopoietic activity to systematically compare hematopoietic progenitors and the endothelial niche. We predict stage-specific interactions accompanying the transition of yolk sac endothelium to primitive and definitive hematopoietic fates and reveal distinct roles for fetal liver vascular niches. Furthermore, we provide in vitro evidence that lipid signaling by sphingosine-1-phosphate producing erythrocyte progenitors supports hematopoietic stem cell expansion in fetal liver. Our resource deciphers the temporal waves of hematopoietic development within distinct vascular niches.
2025-06-30 | GSE229427 | GEO
Project description:Hematopoiesis occurs in distinct waves. ‘Definitive’ hematopoietic stem cells (HSC) with the potential for all blood lineages emerge in the aorta-gonado-mesonephros (AGM), while ‘primitive’ progenitors, whose potential is thought to be limited to erythrocytes, megakaryocytes and macrophages (MΦ), arise earlier in the yolk sac (YS). Here, we questioned whether other YS lineages exist that have not been identified, partially owing to limitations of current lineage tracing models. We established the use of Cdh5CreERT2 for hematopoietic fate mapping, which revealed the YS origin of mast cells (MC). YS derived MC are replaced by definitive MC, which maintain themselves independently from the BM in the adult. Replacement occurs with tissue specific kinetics. MC in the skin, but not other organs, remain largely YS derived prenatally and are phenotypically and transcriptomically distinct from definite adult MC. We conclude that dual hematopoietic origin is not MΦ specific, but shared between these two myeloid lineages.
2018-06-01 | GSE104790 | GEO
Project description:Zeb2 has been shown to influence hematopoietic differentiation and loss thereof leads to complex differentiation defects in multiple hematopoietic lineages. We used microarrays to compare the expresssion profile of Zeb2-defective with WT hematopoietic stem cells and identified several dinstict classes of up-regulated genes during this process.
2016-09-24 | GSE87305 | GEO
Project description:Study of loss of ZEB2 in breast cancer cells in vitro and in vivo: gene expression and phenotypic switch to more benign behavior of the cancer cells. Morphological, functional and gene microarray analysis following ZEB2 knockdown in MDAMB231 cells reveals gain of epithelial differentiation, reduction of migration, invasion and metastatic capability. The measurement of ZEB2 transcriptional activity in tumor cells efficiently predicts the probability of breast cancer patient survival. Global gene expression profiles were measured using Affymetrix U133 plus2 microarrays in MDAMB231 cells (control and ZEB2 shRNA and siRNA knockdown cells on plastic)
2016-03-15 | E-GEOD-27966 | biostudies-arrayexpress
Project description:Common primitive-definitive hematopoietic precursors vs. Definitve hematopoietic progenitor cells
| PRJNA209127 | ENA