BCAS2 promotes primitive hematopoiesis by sequestering β-catenin within the nucleus
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ABSTRACT:
PROVIDER: PRJNA1262902 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33570992_1.fastq.gz | Fastqsanger.gz | |||
| SRR33570992_2.fastq.gz | Fastqsanger.gz | |||
| SRR33570993_1.fastq.gz | Fastqsanger.gz | |||
| SRR33570993_2.fastq.gz | Fastqsanger.gz |
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Project description:Breast carcinoma amplified sequence 2 (BCAS2), a core component of the hPrP19 complex, plays crucial roles in various physiological and pathological processes. However, whether BCAS2 has functions other than being a key RNA-splicing regulator within the nucleus remains unknown. Here, we show that BCAS2 is essential for primitive hematopoiesis in zebrafish and mouse embryos. The activation of Wnt/β-catenin signal, which is required for hematopoietic progenitor differentiation, is significantly decreased upon depletion of bcas2 in zebrafish embryos and mouse embryonic fibroblasts (MEFs). Interestingly, BCAS2 deficiency has no obvious impact on the splicing efficiency of β-catenin pre-mRNA, while significantly attenuating β-catenin nuclear accumulation. Moreover, we find that BCAS2 directly binds to β-catenin via its coiled-coil domains, thereby sequestering β-catenin within the nucleus. Thus, our results uncover a previously unknown function of BCAS2 in promoting Wnt signaling by enhancing β-catenin nuclear retention during primitive hematopoiesis.
2025-06-05 | GSE297155 | 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: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:The splicing factor Bcas2 is involved in several biological processes including tumorigenesis, gametogenesis, and hematopoiesis. The alternative splicing events and downstream genes regulated by Bcas2 have not yet been investigated at the transcriptome level in zebrafish. In this study, we conducted RNA-sequencing analysis on the WT and bcas2 knockout zebrafish embryos (3 dpf) to identify the global differentially expressed genes (DEGs) and differential splicing events (DSEs). 868 DEGs (293 up and 575 down) were identified and genes related to spliceosome, mRNA splicing, and mRNA processing were significantly upregulated, suggesting a negative feedback of the splicing pathway. Besides, 664 DSEs related to 593 genes were identified and sequence signature analysis of these DSEs revealed that the alternatively spliced exons affected by bcas2 knockout have relatively shorter length, longer upstream and downstream introns, and weaker 5’ or 3’ splicing sites, when compared with the control exons. Furthermore, we demonstrated that the exon 5 of ikzf1 gene, a transcription factor related to lymphocyte differentiation, was preferably skipped in the bcas2 knockout embryos, resulting in the deletion of 11 aa between the two conserved zinc finger domains of Ikzf1. Accordingly, several downstream genes, such as rasgrp2 and rgs2, were significantly downregulated and the lymphocyte generation was impaired in the bcas2 knockout embryos. Taken together, our work depicts the global changes of gene expression and alternative splicing caused by bcas2 knockout in zebrafish embryos and reveals an important role of Bcas2-regulated alternative splicing of ikzf1 in lymphoid hematopoiesis.
2024-06-01 | GSE246374 | GEO
Project description:cMaf supports Zeb2 expression for primitive hematopoiesis (Multiome)
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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:Previously, we have confirmed the tumor suppressive role of Estrogen Related Receptor β (ERRβ) in breast cancer by modulation of ER transcriptional activities on Breast Cancer Amplified Sequence 2 (BCAS2) and Follistatin(FST).In the mentioned study, we proved downregulation of Cyclin D1 by BCAS2.In the previous report, we have also proved downregulation of FST by BCAS2 through inhibition of β-catenin/TCF-4 complex recruitment on FST promoter. Interestingly, Cyclin D1 induction by FST has been also reported by a different group.Recently, Cyclin D1 expression has been found to be associated with DICER1 induction. Hence it may be speculated, that a part of miRNA population, which involves Dicer for processing, is regulated by BCAS2. And it is also possible, that FST may oppose the effect of BCAS2 on those Dicer-processed miRNAs.This Dicer-regulation by Cyclin D1was reported in Luminal A type of breast cancer. Hence, we chose MCF-7 breast cancer cells for miRNA profiling post knocking down BCAS2 and FST.
2017-10-31 | GSE89390 | 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 | GSE284309 | GEO
Project description:cMaf supports Zeb2 expression for primitive hematopoiesis (CUT&RUN)
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Project description:MYB is well recognized to be a key regulator of definitive hematopoiesis that plays an important role in the maintenance and multilineage differentiation of hematopoietic stem cells (HSCs). In the vertebrate developmental context, MYB is widely regarded dispensable for primitive hematopoiesis but critically required for the development of definitive hematopoiesis. To explore the role of MYB in human hematopoietic development we have inactivated the gene by bi-allelic TALEN-supported gene targeting in several lines of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), and subjected these cells to hematopoietic differentiation in well-defined cell culture conditions. Venus gene reporter was inserted into the knock-in allele to monitor MYB expression during the course of the hESC/iPSC differentiation. The gene reporter system showed that MYB is specifically expressed during hematopoietic commitment in the earliest primitive blood cells. Moreover, the level of MYB expression was highest at the commitment stage of differentiation and significantly decreased at the maturations stage. We found that MYB was not required for initial hematopoietic commitment of nascent mesoderm and emergence of primitive, yolk sac-type human hematopoietic progenitors. However, inactivation of MYB severely abrogated proliferation of the primitive erythroid and mixed erythroid-macrophage-megakaryocyte progenitors. In addition, MYB-negative hESC/iPSC lines demonstrated major defects in myeloid cell development and completely failed to generate mature granulocytes. Transposon-mediated rescue of MYB expression in MYB-null cells efficiently restored both the primitive hematopoietic progenitors and immature myeloid cells. Our data indicate that in contrast to its previously attributed exclusive role in definitive hematopoiesis, MYB is indispensable for primitive human hematopoiesis.
2021-01-31 | GSE125761 | GEO