Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bcl11a orchestrates multilineage integrity in aging hematopoiesis by regulating multipotent progenitor fate decisions [CUT&Tag]

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE316942 | GEO | 2026/07/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Bcl11a orchestrates multilineage integrity in aging hematopoiesis by regulating multipotent progenitor fate decisions

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

Bcl11a orchestrates multilineage integrity in aging hematopoiesis by regulating multipotent progenitor fate decisions [ATAC-seq]

2026-07-01 | GSE316941 | GEO

EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism [10x]

Project description:Haematopoietic stem cells (HSC) and multipotent progenitor cells (MPP) generate all cells of the blood system, although cellular heterogeneity and bias in lineage potential have been observed. Here, we examined whether lineage-specific transcription factors, such as the B-lineage determinant EBF1, establish lineage bias in early progenitors. We detect low level EBF1 expression in myeloid-biased MPP3 and lymphoid-biased MPP4 cells, and show that Ebf1-deficient animals display reduced HSC quiescence and repopulation capacity, enhanced myelopoiesis and enhanced myeloid differentiation potential of MPP3 and MPP4 cells. Bulk and single-cell RNA-seq analysis revealed a CEBPa-driven myeloid transcriptome in Ebf1-deficient progenitors, and we find that EBF1 binds and potentially antagonizes the haematopoietic Cebpa enhancer. In MPP3 cells, EBF1 additionally primes enhancers associated with B-lymphoid genes that gain expression in common lymphoid progenitors. Thus, our study identifies EBF1 as an important determinant in regulating the balance of myeloid versus lymphoid potential in the earliest hematopoietic progenitors.

2022-06-30 | GSE189051 | GEO

EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism [Bulk RNA-seq]

2022-06-30 | GSE188884 | GEO

EBF1 contributes to the balance of lympho-myeloid fate in haematopoietic progenitors via B-lymphoid priming and Cebpa antagonism [ATAC-seq]

2022-06-30 | GSE189049 | GEO

Stromal inflammation is a targetable driver of hematopoietic aging [Microarray analysis]

Project description:We performed integrated analyses of hematopoietic stem and progenitor cells as well as bone marrow stromal cells to better understand the underlying mechanisms of blood aging. To determine how the molecular state of multipotent progenitor (MPP) cells change with age we performed transcriptomic analyses of myeloid-biased MPP3 and lymphoid-biased MPP4 populations from young and old mice.

2022-11-02 | GSE168661 | GEO

A single cell framework identifies functionally and molecularly distinct multipotent progenitors in adult human hematopoiesis

Project description:Hematopoietic multipotent progenitors (MPPs) regulate blood cell production to appropriately meet the biological demands of the human body. Human MPPs remain ill-defined whereas mouse MPPs have been well characterized with distinct immunophenotypes and lineage potencies. Using multiomic single cell analyses and complementary functional assays, we identified new human MPPs and oligopotent progenitor populations within Lin-CD34+CD38dim/lo adult bone marrow with distinct biomolecular and functional properties. These populations were prospectively isolated based on expression of CD69, CLL1, and CD2 in addition to classical markers like CD90 and CD45RA. We show that within the canonical Lin-CD34+CD38dim/loCD90-CD45RA- MPP population, there is a CD69+ MPP with long-term engraftment and multilineage differentiation potential, a CLL1+ myeloid-biased MPP, and a CLL1-CD69- erythroid-biased MPP. We also show that the canonical Lin-CD34+CD38dim/loCD90-CD45RA+ LMPP population can be separated into a CD2+ LMPP with lymphoid and myeloid potential, a CD2- LMPP with high lymphoid potential, and a CLL1+ GMP with minimal lymphoid potential. We used these new HSPC profiles to study human and mouse bone marrow cells and observe limited cell type specific homology between humans and mice and cell type specific changes associated with aging. By identifying and functionally characterizing new adult MPP sub-populations, we provide an updated reference and framework for future studies in human hematopoiesis.

2025-07-31 | GSE262440 | GEO

Unfolded protein response signaling promotes myeloid cell production and cooperates with oncogenic mutation

Project description:Unfolded protein response (UPR) is an evolutionally conserved adaptive mechanism that promotes protein homeostasis under endoplasmic reticulum (ER) stress. UPR signaling has numerous functions in metabolism, cancer, immunology, and neurodegenerative diseases. Recent studies also showed that UPR signaling has important roles in hematopoietic stem and progenitor cell biology. However, whether UPR signaling regulates hematopoietic lineage fate decision remains elusive. Here, we found that FcgR- MPP3 generates erythroid lineage and Jak2V617F mutation leads to overproduction of erythroid cells by expanding FcgR- MPP3. We showed that UPR signaling increases myeloid cell production through promoting FcgR- MPP3 transition to granulocyte/macrophage progenitor (GMP) producing FcgR+ MPP3 at the expense of erythroid lineage via the XBP1 pathway. Under a disease condition, UPR signaling cooperates with Jak2V617F mutation and exacerbates disease phenotype as increasing red blood cells in a mouse model of polycythemia vera (PV) through the ATF4 pathway. Activation of UPR signaling also increased myeloid output in healthy donor bone marrow MPP cells while skewing the output towards erythroid lineage in PV patient bone marrow MPP cells. Together, our results identify a novel function of UPR signaling in hematopoietic lineage specification and provide critical insights into targeting UPR signaling in hematological malignancies.

2026-02-18 | GSE297249 | GEO

Effect of depletion of the transcriptional factor FoxP1 on gene expression in mouse normal adult hematopoietic stem and progenitor cells.

Project description:Transcription factor Forkhead box P1 (FOXP1) is a key regulator of various immune cell functions, including monocyte differentiation, B cell terminal differentiation and CD4+ or CD8+ T cell quiescence. In previous studies, we have shown that FOXP1 contributes to human hematopoietic stem progenitor cell (HSPC) and acute myeloid leukemia (AML) cell growth. Here we investigated the in vivo role of Foxp1 in early adult murine hematopoiesis. We showed that hematopoietic-speciﬁc loss of Foxp1 expression leads to attrition of the medullar HSC/Multipotent progenitor (MPP)-1 compartment in parallel with an enhancement of the myeloid-biased MPP3 compartment, without impact on MPP2 or MPP4 compartments. Foxp1-deﬁcient HSCs exhibited a reduced self-renewal capacity in competitive hematopoietic reconstitution assays, and HSC and all MPP compartments showed enhanced proliferation with a G0 phase reduction. To further investigate the role of Foxp1 in the regulation of HSC and MPP compartments, we performed gene expression profiling analysis of HSC/MPP1 and MPP3 compartments from WT and Foxp1-deficient mice using data obtained from RNASeq of 3 different cell populations.

2025-06-20 | GSE268789 | GEO

Multipotent progenitors with distinct origins, clonal lineage fates, transcriptomes, and surface markers yield two hematopoietic trees

Project description:Multipotent progenitors (MPP) are the quantitative source of native hematopoiesis that have been thought to be replenished slowly by hematopoietic stem cells (HSC). However, recent fate mapping studies have revealed two developmentally distinct populations of MPP, HSC-derived MPP (hMPP), and HSC-independent, embryonic MPP (eMPP). These data raise fundamental questions on the distinctions and functions of these progenitors. Here, we mapped the clonal dynamics of the two independent MPP systems, using in situ barcoding, and barcode linkage (hMPP), or disconnect (eMPP), with HSC. The cumulative output of eMPP to hematopoiesis was 35%, and their output was enriched for lymphoid fates. Conversely, hMPP output was enriched for myeloid-restricted fates. Distinguishing HSC from eMPP outputs revealed that only ~15% of adult HSC clones underwent multilineage differentiation (lymphoid, myeloid, and erythroid). To prospectively identify eMPP, we developed PolySMART for joint profiling of PolyloxExpress RNA barcodes, surface markers, and transcriptomes, and we found that the plasma cell marker CD138 enriches for eMPP. CD138+ MPP are primed for self-renewal and toward lymphoid fate, and become largely but not completely replaced by CD138− MPP over time, which may contribute to the loss of lymphoid output with age. Taken together, adult hematopoiesis consists of two distinct lineage trees. The source of the “eMPP tree” substantially contributes to hematopoiesis before it declines, while the HSC-hMPP tree supplies hematopoiesis life-long. Our molecular determinants distinguishing the two MPP systems may open avenues to further explore these unexpected layers of hematopoiesis.

2025-11-05 | GSE272588 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data