Myeloid-biased HSC require Semaphorin 4A from the bone marrow niche for self-renewal under stress and life-long persistence
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PROVIDER: PRJEB52992 | ENA |
REPOSITORIES: ENA
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Project description:Tissue stem cells are hierarchically organized, but the signals that selectively preserve their functional integrity are largely unknown. Semaphorin 4A (Sema4A) is a specific regulator of myeloid-biased hematopoietic stem cells (myHSC), which are positioned at the top of the HSC hierarchy. Through single-cell transcriptomics, we compare the effect of Sema4A knock-out on the myHSCs.
2023-06-04 | E-MTAB-12890 | biostudies-arrayexpress
Project description:Tissue stem cells are hierarchically organized, but the signals that selectively preserve their functional integrity are largely unknown. Semaphorin 4A (Sema4A) is a specific regulator of myeloid-biased hematopoietic stem cells (myHSC), which are positioned at the top of the HSC hierarchy. Through single-cell transcriptomics, we compare the effect of Sema4A knock-out on the myHSCs.
2022-01-21 | E-MTAB-11359 | biostudies-arrayexpress
Project description:Using RNA sequencing analysis on myeloid biased HSC, we compared gene expression profiles between WT and Igf2bp2 knock-out mice at young and old age. 1421 differentially expressed genes were identified in young myeloid biased HSC from Igf2bp2 knock-out mice compared to young WT; however, only 26 differentially expressed genes were identified in old myeloid biased HSC from Igf2bp2 knock-out mice compared to old WT. Compared to young WT myeloid biased HSC, myeloid biased HSC from young Igf2bp2 knock-out exhibits reduced expression of genes involved in metabolism and translation. In addition, single cell RNA sequencing analysis of myeloid biased HSC in young wildtype mice identified nine sub-clusters. HSCs from a sub-cluster with high expression of Igf2bp2 exhibit up-regulated IGF/PI3K/AKT signaling and increased expression of genes involved in HSC quiescence and maintenance. Altogether, the study provides a correlation and mechanism to understand the role of Igf2bp2 in HSC function and aging.
2021-02-05 | GSE166176 | GEO
Project description:Array analysis of My-bi and Ly-bi HSC identifies candidate molecules for myeloid-bias. Collectively the data show that HSC in adults are largely epigenetically fixed in differentiation and self-renewal behavior. A direct examination of the epigenetic mechanisms that imprint HSC is difficult. However, an indirect way of assessing the effects of epigenetic imprinting is to look for the expressed gene programs of different types of HSC. Therefore, we performed an array analysis in collaboration with Dr. Michael Cooke. My-bi and Ly-bi HSC were identified in clonally repopulated hosts. The analysis returned 218 differentially expressed genes (M-bM-^IM-% Log2 M-bM-^IM-%2, p< 0.05) of which 36 were found to be overexpressed in My-bi HSC and the rest was overexpressed in Ly-bi HSC (Appendix A). There was no difference in expression levels for genes known to be involved in fate decisions during differentiation. This agrees well with our data that lineage bias is a stable function of a HSC, and does not reflect a differentiated type of cell. Gene expression profiles of myeloid-biased (My-bi) and lymphoid-biased (Ly-bi) stem cells were analyzed. Clonally repopulated hosts were generated by limiting dilution of bone marrow into ablated hosts and lineage bias was determined. Single My-bi (Tenor) and Ly-bi (Mort) repopulated hosts were sacrificed and Donor type HSC were enriched for Sca-1+, Lin- cells. Two technical replicates of RNA extract were run from each clone.
2013-05-01 | E-GEOD-41702 | biostudies-arrayexpress
Project description:Although Semaphorin 3G has some roles in the development of vessels, the roles in immune system are not characterized. We aimed to study how Semaphorin 3G affects the function of macrophages.
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Project description:Bulk and single RNA sequencing on the role of Igf2bp2 in myeloid-biased HSC
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Project description:The Hematopoietically-expressed homeobox transcription factor (Hhex) is important for the maturation of definitive hematopoietic progenitors and B-cells during development. We have recently shown that in adult hematopoiesis, Hhex is dispensable for maintenance of hematopoietic stem cells (HSCs) and myeloid lineages but essential for the commitment of Common Lymphoid Progenitors (CLPs) to lymphoid lineages. However, whether Hhex plays a role in HSC self-renewal and myeloid expansion during hematopoietic stress is unknown. Here we show that during serial bone marrow transplantation, Hhex-deleted HSCs are progressively lost, revealing an intrinsic defect in HSC self-renewal. Moreover, Hhex-deleted mice show markedly impaired hematopoietic recovery following myeloablation. In vitro, Hhex-null blast colonies were incapable of replating, implying a specific requirement for Hhex in immature hematopoietic progenitors. Transcriptome analysis of Hhex-null Lin-Sca+Kit+ (LSK) cells showed that Hhex deletion leads to the deregulation of Polycomb Repressive Complex 2 (PRC2) target genes, including an upregulation of Cdkn2a locus, encoding the cell cycle repressors p16Ink4a and p19Arf. Indeed, loss of Cdkn2a restored Hhex-null blast colony replating in vitro, as well as hematopoietic reconstitution following myeloablation in vivo. Thus, HSCs require Hhex to repress Cdkn2a to enable continued self-renewal and response to hematopoietic stress.
2017-05-22 | GSE86209 | GEO
Project description:The hematopoietic stem cell (HSC) compartment is heterogeneous, yet our understanding of the identities of different HSC subtypes is limited. Here we show that platelet integrin CD41 (M-NM-1IIb), currently thought to only transiently mark fetal HSCs, is expressed on an adult HSC subtype that accumulates with age. CD41+ HSCs were largely quiescent and exhibited myeloerythroid and megakaryocyte gene priming, governed by Gata1, whereas CD41- HSCs were more proliferative and exhibited lymphoid gene priming. When isolated without the use of blocking antibodies, CD41+ HSCs possessed long-term repopulation capacity upon serial transplantations and showed a marked myeloid-bias compared to CD41-HSCs, which yielded a more lymphoid-biased progeny. CD41-knockout mice displayed multilineage hematopoietic defects coupled with decreased quiescence and survival of HSCs, suggesting that CD41 is functionally relevant for HSC maintenance and hematopoietic homeostasis. Transplantation experiments indicated that CD41-KO associated defects are long-term transplantable and HSC-derived, and in part mediated through the loss of platelet mass leading to decreases in HSC exposure to important platelet released cytokines, such as TGFM-NM-21. In summary, our data provide a novel marker to identify a myeloid-biased HSC subtype that becomes prevalent with age, and highlights the dogma of HSC regulation by their progeny. For microarray analysis, 1000 HSCs were FACS sorted from pools of 4-5 mice directly into lysis buffer, RNA extracted and whole transcript amplification was performed as previously described (Gonzalez-Roca E, Garcia-Albeniz X, Rodriguez-Mulero S, Gomis RR, Kornacker K, Auer H. Accurate expression profiling of very small cell populations. PLoS One. 2010;5:e14418.)
2013-04-11 | E-GEOD-45561 | biostudies-arrayexpress
Project description:The hematopoietic stem cell (HSC) compartment is heterogeneous, yet our understanding of the identities of different HSC subtypes is limited. Here we show that platelet integrin CD41 (αIIb), currently thought to only transiently mark fetal HSCs, is expressed on an adult HSC subtype that accumulates with age. CD41+ HSCs were largely quiescent and exhibited myeloerythroid and megakaryocyte gene priming, governed by Gata1, whereas CD41- HSCs were more proliferative and exhibited lymphoid gene priming. When isolated without the use of blocking antibodies, CD41+ HSCs possessed long-term repopulation capacity upon serial transplantations and showed a marked myeloid-bias compared to CD41-HSCs, which yielded a more lymphoid-biased progeny. CD41-knockout mice displayed multilineage hematopoietic defects coupled with decreased quiescence and survival of HSCs, suggesting that CD41 is functionally relevant for HSC maintenance and hematopoietic homeostasis. Transplantation experiments indicated that CD41-KO associated defects are long-term transplantable and HSC-derived, and in part mediated through the loss of platelet mass leading to decreases in HSC exposure to important platelet released cytokines, such as TGFβ1. In summary, our data provide a novel marker to identify a myeloid-biased HSC subtype that becomes prevalent with age, and highlights the dogma of HSC regulation by their progeny.
2013-04-11 | GSE45561 | GEO
Project description:To identify the molecular characterisitics of parallel lineage-biased MPP populations arising from hematopoietic stem cells (HSC) we conducted genome-wide analyses of hematopoietic stem, progenitor and mature myeloid cell populations using Affymetrix Gene ST1.0 arrays. Microarray analysis of 3-5 biological replicates of the indicated hematopoietic populations, isolated by FACS sorting from C57BL/6 mouse BM. Immunophenotypic definitions: Long-term HSC (HSCLT) (Lin-/cKit+/Sca1+/Flk2-/CD48-/CD150+); Short-term HSC (HSCST) (Lin-/cKit+/Sca1+/Flk2-/CD48-/CD150-); MPP2 (Lin-/cKit+/Sca1+/Flk2-/CD48+/CD150+); MPP3 (Lin-/cKit+/Sca1+/Flk2-/CD48+/CD150-); MPP4 (Lin-/cKit+/Sca1+/Flk2+); CMP (Lin-/cKit+/Fc?R-/CD34+); GMP (Lin-/cKit+/Fc?R+/CD34+); Pre-granulocyte (PreGr) (Mac1+/Gr1int); Granulocyte (Gr) (Mac1+/Gr1hi). HSC and GMP samples listed here were also used as controls for our related microarray study GSE48893.
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