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The impact of stanniocalcin 1 on the transcriptome of human cord blood stem/progenitors

ABSTRACT: The impact of stanniocalcin 1 on the transcriptome of human cord blood stem/progenitors

PROVIDER: PRJNA563915 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10068982.fastq.gz	Fastqsanger.gz
	SRR10068983.fastq.gz	Fastqsanger.gz
	SRR10068984.fastq.gz	Fastqsanger.gz
	SRR10068985.fastq.gz	Fastqsanger.gz
	SRR10068986.fastq.gz	Fastqsanger.gz

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Molecular transitions in early progenitors during human cord blood hematopoiesis

Project description:Hematopoietic stem cells give rise to diverse cell types in the blood system, yet our molecular understanding of the earliest fate decisions that generate this enormous diversity in humans remains incomplete. Here we leverage Drop-seq to individually profile more than 20,000 progenitors cells from human cord blood, without prior enrichment or depletion for individual lineages based on surface markers. Our data reveal a transcriptional 'atlas' of progenitor states in human cord blood, which we leverage to reconstruct differentiation trajectories from HSC to four downstream lineages. And we also demonstrate that Drop-seq data can be utilized to identify new heterogeneous markers of cell state.

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Project description:In mice, two restricted DC progenitors, macrophage-dendritic progenitor (MDP) and common dendritic cell progenitor (CDP) demonstrate increasing commitment of DC lineage as they sequentially lose granulocyte and monocyte potential respectively. Identifying these progenitors has enabled understanding of the role of DCs and monocytes in immunity and tolerance in mice. In humans, however, restricted monocyte and DC progenitors remain unknown. Progress in studying human DC development has been hampered by lack of an in vitro culture system that recapitulates in vivo DC hematopoiesis. Here we report a culture system that supports development of CD34+ hematopoietic stem cell progenitors into the three major human DC subsets, monocytes, granulocytes, NK and B cells. Using this culture system we defined the pathway for human DC development, and revealed the sequential origin of human DCs from increasingly restricted progenitors: a granulocyte-monocyte-DC progenitor (hGMDP) that develops into a monocyte-DC progenitor (hMDP) that develops into monocytes and a common DC progenitor (hCDP) that is restricted to produce the three major DC subsets. The phenotype of the DC progenitors partially overlaps with granulocyte monocyte progenitors (GMPs). These progenitors reside in human cord blood and bone marrow but not in the blood or lymphoid tissues in the steady state. We performed whole transcriptome expression analysis on monocytes and subsets of dendritic cells i.e. CD1c+ DCs, CD141+ DCs and CD303+ pDCs isolated from blood or differentiated in culture from cord blood CD34+ cells in presence of MS5 stromal cells and Flt3l, GM-CSF and SCF cytokines.

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The impact of stanniocalcin 1 on the transcriptome of human cord blood stem/progenitors

Project description:Purpose: Stanniocalcin 1 (STC1) is a secreted glycoprotein expressed in mesenchymal stroma cells (MSCs). STC1 expression is upregulated in response to acute myeloid leukemia (AML) co-culture. Recombinant STC1 has proliferation limiting effects on human hematopoietic stem/progenitors cells (HSPCs) and facilitiates the preservation of HSCs ex vivo. We hope to gain insight into the mechanism by exploring the transcriptome of stem/progenitors exposed to STC1.

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Project description:analysis of differential gene expression in CD34+ derived neutrophil progenitors from umbilical cord blood, in response to Mek1 activation

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