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Expression data from Satb1- and control-transduced LSK Flt3- cells

ABSTRACT: How hematopoietic stem cells (HSCs) produce specific lineages is not well understood. We searched for key factors that direct HSC to lymphopoiesis. Comparing gene expression profiles for HSCs and early lymphoid progenitors revealed that Satb1, a global chromatin regulator, was significantly induced with lymphoid lineage specification. HSCs from Satb1-null mouse were defective in lymphopoietic activity in culture, and failed to reconstitute T-lymphopoiesis in wild-type recipients. Furthermore, Satb1-transduction in HSCs, as well as in embryonic stem cells, robustly promoted their differentiation toward lymphocytes in culture.

ORGANISM(S): Mus musculus

PROVIDER: GSE45566 | GEO | 2013/04/01

SECONDARY ACCESSION(S): PRJNA194583

REPOSITORIES: GEO

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Expression data from Satb1- and control-transduced LSK Flt3- cells

Project description:How hematopoietic stem cells (HSCs) produce specific lineages is not well understood. We searched for key factors that direct HSC to lymphopoiesis. Comparing gene expression profiles for HSCs and early lymphoid progenitors revealed that Satb1, a global chromatin regulator, was significantly induced with lymphoid lineage specification. HSCs from Satb1-null mouse were defective in lymphopoietic activity in culture, and failed to reconstitute T-lymphopoiesis in wild-type recipients. Furthermore, Satb1-transduction in HSCs, as well as in embryonic stem cells, robustly promoted their differentiation toward lymphocytes in culture. We prepared RNA samples from control or Satb1-transfected Lin- c-kitHi Sca-1+ Flt3- cells derived from WT mouse bone marrow.

2013-04-01 | E-GEOD-45566 | biostudies-arrayexpress

Transcriptome analysis of SATB1- and SATB1+ Hematopoietic stem cells.

Project description:Hematopoietic stem cells (HSCs) are now recognized as a heterogeneous population in self-renewing and differentiation capabilities. However, fundamental mechanisms governing the heterogeneity remain uncertain. We here show that special AT-rich sequence-binding protein 1 (SATB1), a global chromatin organizer, is involved in the mechanisms. Analyzing hematological lineage-restricted SATB1 knock out mice proved that SATB1 is indispensable for both self-renewal and normal differentiation of adult HSCs. Using SATB1/Tomato knock-in mice, we subdivided HSCs according to SATB1 intensity. Culture experiments and RNA-sequencing revealed essential differences between SATB1- and SATB1+ HSCs regarding lineage potential.

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Project description:Hematopoietic stem cell (HSC)-independent lymphopoiesis has been elucidated in murine embryos. However, our understanding regarding human embryonic counterparts remains limited. Here, we unveiled the presence of human yolk sac-derived lymphoid-biased progenitors (YSLPs) expressing CD34, IL7R, LTB and IRF8 at Carnegie Stage 10, much earlier than the first HSCs emergence. The number and lymphopoietic potential of these progenitors were both significantly higher in yolk sac than embryo proper at this early stage. Importantly, single-cell/bulk culture and CITE-seq have elucidated the tendency of YSLP differentiating into innate lymphoid cells and dendritic cells. Notably, lymphoid progenitors in fetal liver before and after HSCs seeding displayed distinct transcriptional features, with the former closely resembling those of YSLPs.

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Uncovering human yolk sac-derived innate lymphoid-biased multipotent progenitors prior to hematopoietic stem cell formation (CITE-Seq)

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Lymphoid Biased Hematopoietic Stem Cells are Maintained with Age and Retain Normal Developmental Potential in the Absence of Inflammatory Stimuli

Project description:The hematopoietic stem cell (HSC) compartment includes lymphoid biased (Ly-HSCs) and myeloid biased (My-HSCs) subsets. Current models propose that the number of Ly-HSCs declines with age and this contributes to the diminution of lymphopoiesis that is a feature of aging. This view is based on a reduction in the frequency of Ly-HSCs in old bone marrow, but we now show that when total HSCs are taken into account, the number of Ly-HSCs is not reduced in old mice. We further demonstrate that old Ly-HSCs exhibit a normal capacity to produce lymphoid progenitors when removed from the bone marrow. However, the production of inflammatory cytokines is known to increase with age, and when Ly-HSCs are exposed to these mediators, lymphocyte production is blocked. We also demonstrate that old Ly-HSCs generate myeloid cells that phenotypically resemble those produced by old My-HSCs, a finding consistent with the myeloid biased gene expression pattern of old Ly-HSCs. These observations indicate that current models of how aging impacts the lymphopoietic potential of HSCs need to be revised and point to changes in the in vivo environment, rather than intrinsic changes in HSCs, as the principal cause of the reduced lymphopoiesis and increased myelopoiesis during aging.

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Analysis of differentially expressed genes in murine Satb1-deficient hematopoietic stem cells (HSCs) compared to wild-type HSCs

Project description:Gene expression analysis on purified murine hematopoietic stem cells (HSCs) deficient for Special AT-rich sequence-binding protein 1 (Satb1) compared to wild-type HSCs. Analysis of gene expression of bone marrow-derived CD45.2+ CD150+cKit+Sca-1+CD4-CD8a-CD19-B220-Gr-1- HSCs from congenic recipient animals transplanted >20 weeks with either wild-type or Satb1-deficient hematopoeitic cells.

2013-04-07 | E-GEOD-44107 | biostudies-arrayexpress

Expression data in WT and Satb1-/- ES cells

Project description:Satb1 and Satb2 are regulators of higher order chromatin in T cells and osteoblasts repectively. We were interested if Satb1 and Satb2 play a role in the regulation of gene expression in ES cells. In this experiment, we compared the transcriptome of wild type and Satb1-/- ES cells. Interestingly Satb1-/- ES cells display an impaired differentiation potential. WT and Satb1-/- ES cells were grown for 3 days in the presence of LIF and selected for Oct4-expression cells by the addition of hygromycin to the culture medium. Previously the cells had been engineered so that they contain a selectable HygroTK reporter in the the Oct4 locus. Total RNA was harvested and used for hybridization.

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Analysis of differentially expressed genes in murine Satb1-deficient hematopoietic stem cells (HSCs) compared to wild-type HSCs

Project description:Gene expression analysis on purified murine hematopoietic stem cells (HSCs) deficient for Special AT-rich sequence-binding protein 1 (Satb1) compared to wild-type HSCs.

2013-04-07 | GSE44107 | GEO

Genome-wide maps of DNA cytosine methylation state in during normal differentiation commitment in hematopoietic stem cells (HSC) and in Special AT-rich sequence-binding protein1 (Satb1) - deficient HSC

Project description:Our data show Satb1 deficiency leads to alterations in DNA cytosine methylation and a commitment-primed epigenetic state in HSCs. Examination of DNA cytosine methylation in wild type HSC and differentiation-committed progenitors as well as in wild type HSC and HSC lacking Satb1 (n=2 each).

2013-04-07 | E-GEOD-44304 | biostudies-arrayexpress

Transcriptome of SATB1 transduced Hut78 cells

Project description:Hut78 cell line was used as Sezary syndrome cell model. Comparative transcriptome profiles of SATB1 transduced Hut78 cells (Hut78-SATB1) relative to empty MIG vector transduced control Hut78 cells (Hut78-MIG) were analyzed. The primary goal is to establish a list of genes with differential expression between SATB1 transduced Hut78 cells and control Hut78 cells to identify the gene expression regulation effect of SATB1 expression in Sezary cells. Two color experiment, 3 biological replicates (3 unique cell clones) with Hut78 cells, each compared with a distinct individual clone from cells transduced with empty MIG vector.

2011-12-01 | E-GEOD-24951 | biostudies-arrayexpress

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