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Initial seeding of the embryonic thymus by an immune-restricted lympho-myeloid progenitor independently of Notch signaling

ABSTRACT: Gene expression analysis of purified thymopoiesis-initiating progenitors/early thymic progenitors, lymphoid primed multipotent progenitors (LMPP) and hematopoietic stem/progenitor cells from E11.5, E12.5, E13.5 embryos, neonatal (1 week old) and adult (8 weeks old) mice

ORGANISM(S): Mus musculus

PROVIDER: GSE76140 | GEO | 2016/09/26

SECONDARY ACCESSION(S): PRJNA306426

REPOSITORIES: GEO

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Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors.

Project description:The final stages of restriction to the T cell lineage occur in the thymus after the entry of thymus-seeding progenitors (TSPs). The identity and lineage potential of TSPs remains unclear. Because the first embryonic TSPs enter a non-vascularized thymic rudiment, we were able to directly image and establish the functional and molecular properties of embryonic thymopoiesis-initiating progenitors (T-IPs) before their entry into the thymus and activation of Notch signaling. T-IPs did not include multipotent stem cells or molecular evidence of T cell-restricted progenitors. Instead, single-cell molecular and functional analysis demonstrated that most fetal T-IPs expressed genes of and had the potential to develop into lymphoid as well as myeloid components of the immune system. Moreover, studies of embryos deficient in the transcriptional regulator RBPJ demonstrated that canonical Notch signaling was not involved in pre-thymic restriction to the T cell lineage or the migration of T-IPs.

| S-EPMC5172420 | biostudies-literature

Single Cell RNA sequencing analysis of human haemopoietic lympho-myeloid progenitor populations (LMPP, MLP and GMP)

Project description:We performed single cell RNA sequencing of human haemopoietic lympho-myeloid progenitors with the aim to separate functionally and transcriptionally distinct progenitors within the heterogeneous GMP, LMPP and MLP populations. We performed RNA sequencing in a total of 415 single cells. From donors 1 (CB369) and 2 (CB431), 163/166 and 157/249 cells passed quality control.We further analysed the 320 single cells that passed quality control from two different donors (157 and 163 from each donor; 91 LMPP, 110 MLP and 119 GMP). We performed clustering using Seurat package, which identified 3 clusters of cells. We identified genes that were differentially expressed among cells of the different clusters. The majority of the cells in cluster 1 were MLP, the majority of cluster 3 were GMP while cluster comprised of LMPP and GMP cells. Cluster 1 showed high expression of lymphoid-affiliated genes. Conversely, cluster 3 showed increased expression of myeloid genes, while cluster 2 showed a mixed transcriptional signature. PCA analysis revealed a transcriptional continuum of LMPP, MLP and GMP populations.

2017-11-11 | GSE100618 | GEO

Transcripts with H3K36me3 modification at differente stages of pancreas organogensis [CUT&Tag]

Project description:To find the genes with H3K36me3 modificaiton at different stages of pancreas development, we isolated the pancreatic epithelial cells from E11.5, E13.5 and E15.5 fetal pancreas. Considering the low expression of H3K36me3 at E11.5, E11.5 samples worked as a "negantive" control. By compared with the peaks of E11.5, we was able to find genes under direct regulation of H3K36me3 at E13.5 and E15.5.

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Integrated scRNA-Seq Identifies Human Postnatal Thymus Seeding Progenitors and Regulatory Dynamics of Differentiating Immature Thymocytes

Project description:During postnatal life, thymopoiesis depends on the continuous colonization of the thymus by bone marrow-derived hematopoietic progenitors that migrate through the bloodstream. The current understanding of the nature of thymic immigrants is largely based on data from pre-clinical models. Here, we employed single-cell RNA sequencing (scRNA-seq) to examine the immature postnatal thymocyte population in humans. Integration of bone marrow and peripheral blood precursor datasets identified two putative thymus seeding precursors that varied in expression of CD7; CD10; and the homing receptors CCR7, CCR9, and ITGB7. Whereas both precursors supported T cell development, only one contributed to intrathymic dendritic cell (DC) differentiation, predominantly of plasmacytoid dendritic cells. Trajectory inference delineated the transcriptional dynamics underlying early human T lineage development, enabling prediction of transcription factor (TF) modules that drive stage-specific steps of human T cell development. This comprehensive dataset defines the expression signature of immature human thymocytes and provides a resource for the further study of human thymopoiesis.

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Common lymphoid progenitor-independent pathways of innate and T lymphocyte development

Project description:All lymphocytes are thought to develop from common lymphoid progenitors (CLPs). However, lymphoid-primed multi-potent progenitors (LMPPs) are more efficient than CLPs in differentiating into T cells and group 2 innate lymphoid cells (ILC2s). Here, we have divided LMPPs into CD127− (LMPP-s) and CD127+ (LMPP+s) subsets and compared them with Ly6D− and Ly6D+ CLPs. Adult LMPP+s differentiated into T cells and ILCs more rapidly and efficiently than other progenitors in transplantation assays. The development of T cells and ILC2s is highly active in the neonatal period. Neonatal CLPs are rare and, unlike prominent neonatal LMPP+s, do not efficiently differentiate into T cells and ILC2s. ILC2s generated in the neonatal period are long-lived and persist in adult tissues. These results suggest that some ILCs and T cells may develop from LMPP+s via CLP-independent pathways.

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Single cell sequencing of dissected mouse mandibular prominence at embryonic day e11.5 and e13.5

Project description:Single cell sequencing of dissected mouse mandibular prominence at embryonic day e11.5 and e13.5

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Chronological expression data from mouse skeletal muscle stem cells

Project description:Satellite cells are the primary source of stem cells for skeletal muscle growth and regeneration. Since adult stem cell maintenance involves a fine balance between intrinsic and extrinsic mechanisms, we performed genome-wide chronological expression profiling to identify the transcriptomic changes involved in acquisition of muscle stem cell characteristics. Muscle samples were isolated from the trunk during development, postnatally and in adult and aged Pax3GFP/+ mice. After digestion, GFP cells were purified via FACS and process for RNA extraction and hybridization on Affymetrix microarrays (Affymetrix Mouse Genome 430 2.0 Arrays). The different ages selected for sample isolation were E11.5-E12.5-E13.5-E14.5-E15.5-E17.5-P1-P12-1MO-2MO-18MO (E, Embryonic days; P, Postnatal days; MO, age in months), covering embryonic and fetal progenitors and proliferant, quiescent satellite cells. The eleven stages were done in triplicate for E11.5-E12.5-E14.5-E15.5-1MO-2MO-18MO, twice for E13.5, 4 times for P1-P12 and 5 times for E17.5, so 36 samples included in the microarray.

2016-06-15 | E-GEOD-63860 | biostudies-arrayexpress

RNAseq comparison of gene expression profiles in ScxGFP positive cells from E11.5, E13.5 and E15.5 hindlimb samples

Project description:RNAs were isolated from FACS sorted ScxGFP positive cells of hindlimbs at E11.5, E13.5 and E15.5, and characterized by RNAseq

2015-03-19 | GSE65179 | GEO

Transcription profiling of mouse embryonic lung development: time course (C57BL/6J)

Project description:We generated gene expression profiles of 5 time points in murine lung development (E11.5, E13.5, E14.5, E16.5 and P5). The goal of this study was to establish a reference data set for exploration of large-scale similarities between transcriptomes in development and cancer. Experiment Overall Design: Whole lung expression profiles from C57BL/6J mice at E11.5 (pooled sample), E13.5, E14.5, E16.5 and P5.

2008-10-20 | E-GEOD-11539 | biostudies-arrayexpress

Cell-autonomous retinoic acid receptor signaling alters enteric nervous system development with stage-specific effects in mice

Project description:Purpose: Determine how blocking retinoic acid receptor (RAR) signaling within enteric neural crest-derived cells (ENCDC) from E11.5 stomach or E13.5 colon alters mRNA abundance. These ENCDC become the enteric nervous system. Methods: Enteric nervous system precursors were isolated from mouse E11.5 stomach or E13.5 colon using fluorescence activated cell sorting to purify TdTomato or EYFP expressing cells respectively from fetal bowel. The RarαDN allele encodes a potent RAR dominant negative protein that is expressed after CRE-mediated DNA recombination. Tamoxifen-activated CRE-ERT2 was expressed from the Ret locus for E13.5 colon studies and mice were tamoxifen treated at E10.5 prior to cell sorting. The Wnt1Cre allele was employed for E11.5 stomach studies. RNA-SEQ was performed in quadruplicate using Illumina HiSeq 4000. Sequence reads that passed quality filters were aligned to remove repeat sequences and ribosomal RNA reads and then processed using RNA-Seq unified mapper (RUM) package. RUM files were visualized in the TessLA browser for subsequent analyses. Results: Transcriptional profiling shows RarαDN differentially impacts gene expression in E11.5 stomach and E13.5 colon enteric neural crest-derived cells (ENCDC) that become the enteric nervous system. Conclusions: Blocking of RAR signaling in ENCDC causes dramatic changes in gene expression during early development in a stage-specific manner.

2021-02-04 | GSE165344 | GEO

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