Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA309701 | ENA |
REPOSITORIES: ENA
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Project description:B cell CLL/lymphoma 11A (BCL11A) is a transcription factor and regulator of hemoglobin switching that has emerged as a promising therapeutic target for sickle cell disease and thalassemia. In the hematopoietic system, BCL11A is required for B lymphopoiesis, yet its role in other hematopoietic cells, especially hematopoietic stem cells (HSCs) remains elusive. The extensive expression of BCL11A in hematopoiesis implicates context-dependent roles, highlighting the importance of fully characterizing its function as part of ongoing efforts for stem cell therapy and regenerative medicine. Here, we demonstrate that BCL11A is indispensable for normal HSC function. Bcl11a deficiency results in HSC defects, typically observed in the aging hematopoietic system. We find that downregulation of cyclin-dependent kinase 6 (Cdk6), and the ensuing cell-cycle delay, correlate with HSC dysfunction. Our studies define a mechanism for BCL11A in regulation of HSC function and have important implications for the design of therapeutic approaches to targeting BCL11A.
2016-09-20 | GSE77207 | GEO
Project description:To explore the mechanisms by which DCAF8 deficiency induces functional defects in hematopoietic stem cells with an aging-like phenotype, and given DCAF8’s role as a substrate receptor in the E3 ubiquitin ligase complex, we conducted proteomic analysis on Lineage negative bone marrow cells from wild-type and Dcaf8 knockout mice. This analysis aimed to identify protein alterations, providing insights into potential substrates of DCAF8 in murine hematopoietic cells.
2025-10-04 | PXD056107 | Pride
Project description:To explore the mechanisms by which DCAF8 deficiency induces functional defects in hematopoietic stem cells with an aging-like phenotype, and given DCAF8’s role as a substrate receptor in the E3 ubiquitin ligase complex, we conducted ubiquitin proteomic analysis on bone marrow cells from wild-type and Dcaf8 knockout mice. This analysis aimed to identify ubiquitinated proteins and assess changes in ubiquitination, providing insights into potential substrates of DCAF8 in murine hematopoietic cells.
2025-10-04 | PXD056263 | Pride
Project description:To explore the mechanisms by which DCAF8 deficiency induces functional defects in hematopoietic stem cells with an aging-like phenotype, and given DCAF8’s role as a substrate receptor in the E3 ubiquitin ligase complex, we conducted ubiquitin proteomic analysis on bone marrow cells from wild-type and Dcaf8 knockout mice. This analysis aimed to identify ubiquitinated proteins and assess changes in ubiquitination, providing insights into potential substrates of DCAF8 in murine hematopoietic cells.
2025-10-04 | PXD056221 | Pride
Project description:An aging-like phenotype occurs in Tif1γ-/- hematopoietic stem cells
| PRJNA246388 | ENA
Project description:A transcriptome study in mouse hematopoietic stem cells was performed using a sensitive SAGE method, in an attempt to detect medium and low abundant transcripts expressed in these cells. Among a total of 31,380 unique transcript, 17,326 (55%) known genes were detected, 14,054 (45%) low-copy transcripts that have no matches to currently known genes. 3,899 (23%) were alternatively spliced transcripts of the known genes and 3,754 (22%) represent anti-sense transcripts from known genes.
2009-05-20 | GSE16139 | GEO
Project description:Deletion of the NF-κB subunit p65/RelA in the hematopoietic compartment leads to defects in hematopoietic stem cell function.
| PRJNA196174 | ENA
Project description:A transcriptome study in mouse hematopoietic stem cells was performed using a sensitive SAGE method, in an attempt to detect medium and low abundant transcripts expressed in these cells. Among a total of 31,380 unique transcript, 17,326 (55%) known genes were detected, 14,054 (45%) low-copy transcripts that have no matches to currently known genes. 3,899 (23%) were alternatively spliced transcripts of the known genes and 3,754 (22%) represent anti-sense transcripts from known genes. Mouse hematopoietic stem cells were purified from bone marrow cells using negative and positive selection with a Magnetic-Activated Cell Sorter (MACS). total RNA and mRNA were purified from the purified cells using Trizol reagent and magnetic oligo dT beads. Double strand cDNAs were synthesized using a cDNA synthesis kit and anchored oligo dT primers. After NlaIII digestion, 3’ cDNAs were isolated and amplified through 16-cycle PCR. SAGE tags were released from the 3’ cDNA after linker ligation. Ditags were formed, concatemerized and cloned into a pZERO vector. Sequencing reactions were performed with the ET sequencing terminator kit. Sequences were collected using a Megabase 1000 sequencer. SAGE tag sequences were extracted using SAGE 2000 software.
2009-05-20 | E-GEOD-16139 | biostudies-arrayexpress
Project description:Aging hematopoiesis is characterized by myeloid skewing and impaired lymphoid output, a phenomenon traditionally attributed to intrinsic deterioration of hematopoietic stem cells (HSCs). Here, we demonstrate that aging-associated hematopoietic dysfunction is critically shaped at the level of multipotent progenitors (MPPs). We show that aging drives coordinated functional alterations across the MPP compartment, with expansion and reinforced myeloid output of MPP3 accompanied by functional attrition of lymphoid-primed MPP4, collectively exacerbating lineage imbalance. We identify Bcl11a as a dose-dependent regulator of MPP fate that preserves progenitor quiescence and lineage plasticity. Mechanistically, Bcl11a restrains premature myeloid activation by maintaining MPP3 quiescence through repression of the tyrosine kinase Fer, while simultaneously sustaining latent lymphoid potential via activation of the Irf8–Ebf1 transcriptional axis. Importantly, enhancing Bcl11a expression in aged mice restores balanced myeloid and lymphoid output, reprograms aging-associated transcriptional signatures, and rejuvenates multilineage hematopoietic function. Together, these findings establish Bcl11a as a central regulator of progenitor resilience during aging and identify MPPs as critical control points for preserving immune competence across the lifespan.
2026-07-01 | GSE317231 | GEO
Project description:Aging hematopoiesis is characterized by myeloid skewing and impaired lymphoid output, a phenomenon traditionally attributed to intrinsic deterioration of hematopoietic stem cells (HSCs). Here, we demonstrate that aging-associated hematopoietic dysfunction is critically shaped at the level of multipotent progenitors (MPPs). We show that aging drives coordinated functional alterations across the MPP compartment, with expansion and reinforced myeloid output of MPP3 accompanied by functional attrition of lymphoid-primed MPP4, collectively exacerbating lineage imbalance. We identify Bcl11a as a dose-dependent regulator of MPP fate that preserves progenitor quiescence and lineage plasticity. Mechanistically, Bcl11a restrains premature myeloid activation by maintaining MPP3 quiescence through repression of the tyrosine kinase Fer, while simultaneously sustaining latent lymphoid potential via activation of the Irf8–Ebf1 transcriptional axis. Importantly, enhancing Bcl11a expression in aged mice restores balanced myeloid and lymphoid output, reprograms aging-associated transcriptional signatures, and rejuvenates multilineage hematopoietic function. Together, these findings establish Bcl11a as a central regulator of progenitor resilience during aging and identify MPPs as critical control points for preserving immune competence across the lifespan.
2026-07-01 | GSE316942 | GEO