Inflammatory signaling regulates fetal hematopoiesis
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE55493 | GEO | 2014/11/12
SECONDARY ACCESSION(S): PRJNA239780
REPOSITORIES: GEO
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Project description:Hamey2017 - Blood stem cell regulatory
network
This model is described in the article:
Reconstructing blood stem
cell regulatory network models from single-cell molecular
profiles
Fiona K. Hamey, Sonia Nestorowa,
Sarah J. Kinston, David G. Kent, Nicola K. Wilson, and Berthold
Göttgens
Proceedings of the National Academy of
Sciences of the United States of America
Abstract:
Adult blood contains a mixture of mature cell types, each
with specialized functions. Single hematopoietic stem cells
(HSCs) have been functionally shown to generate all mature cell
types for the lifetime of the organism. Differentiation of HSCs
toward alternative lineages must be balanced at the population
level by the fate decisions made by individual cells.
Transcription factors play a key role in regulating these
decisions and operate within organized regulatory programs that
can be modeled as transcriptional regulatory networks. As
dysregulation of single HSC fate decisions is linked to fatal
malignancies such as leukemia, it is important to understand
how these decisions are controlled on a cell-by-cell basis.
Here we developed and applied a network inference method,
exploiting the ability to infer dynamic information from
single-cell snapshot expression data based on expression
profiles of 48 genes in 2,167 blood stem and progenitor cells.
This approach allowed us to infer transcriptional regulatory
network models that recapitulated differentiation of HSCs into
progenitor cell types, focusing on trajectories toward
megakaryocyte–erythrocyte progenitors and lymphoid-primed
multipotent progenitors. By comparing these two models, we
identified and subsequently experimentally validated a
difference in the regulation of nuclear factor, erythroid 2
(Nfe2) and core-binding factor, runt domain, alpha subunit 2,
translocated to, 3 homolog (Cbfa2t3h) by the transcription
factor Gata2. Our approach confirms known aspects of
hematopoiesis, provides hypotheses about regulation of HSC
differentiation, and is widely applicable to other hierarchical
biological systems to uncover regulatory relationships.
This model is hosted on
BioModels Database
and identified by:
MODEL1610060000.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-06-09 | MODEL1610060000 | BioModels
Project description:Hamey2017 - Blood stem cell regulatory
network (LMPP network)
This model is described in the article:
Reconstructing blood stem
cell regulatory network models from single-cell molecular
profiles
Fiona K. Hamey, Sonia Nestorowa,
Sarah J. Kinston, David G. Kent, Nicola K. Wilson, and Berthold
Göttgens
Proceedings of the National Academy of
Sciences of the United States of America
Abstract:
Adult blood contains a mixture of mature cell types, each
with specialized functions. Single hematopoietic stem cells
(HSCs) have been functionally shown to generate all mature cell
types for the lifetime of the organism. Differentiation of HSCs
toward alternative lineages must be balanced at the population
level by the fate decisions made by individual cells.
Transcription factors play a key role in regulating these
decisions and operate within organized regulatory programs that
can be modeled as transcriptional regulatory networks. As
dysregulation of single HSC fate decisions is linked to fatal
malignancies such as leukemia, it is important to understand
how these decisions are controlled on a cell-by-cell basis.
Here we developed and applied a network inference method,
exploiting the ability to infer dynamic information from
single-cell snapshot expression data based on expression
profiles of 48 genes in 2,167 blood stem and progenitor cells.
This approach allowed us to infer transcriptional regulatory
network models that recapitulated differentiation of HSCs into
progenitor cell types, focusing on trajectories toward
megakaryocyte–erythrocyte progenitors and lymphoid-primed
multipotent progenitors. By comparing these two models, we
identified and subsequently experimentally validated a
difference in the regulation of nuclear factor, erythroid 2
(Nfe2) and core-binding factor, runt domain, alpha subunit 2,
translocated to, 3 homolog (Cbfa2t3h) by the transcription
factor Gata2. Our approach confirms known aspects of
hematopoiesis, provides hypotheses about regulation of HSC
differentiation, and is widely applicable to other hierarchical
biological systems to uncover regulatory relationships.
This model is hosted on
BioModels Database
and identified by:
MODEL1610060001.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-06-09 | MODEL1610060001 | BioModels
Project description:MTD project_description Inflammation and decreased stem cell function characterize organism aging, yet the relationship between these factors remains incompletely understood. This study shows that aged hematopoietic stem and progenitor cells exhibit increased ground-stage NF-κB activity, which enhances their responsiveness to undergo differentiation and loss of self-renewal in response to inflammation. The study identifies Rad21/cohesin as a critical mediator of NF-κB signals, by increasing chromatin accessibility of inter-/intra-genic and enhancer regions. Rad21/NF-κB are required for normal differentiation, but limit self-renewal of hematopoietic stem cells (HSCs) during aging and inflammation in an NF-κB dependent manner. HSCs from aged mice fail to downregulate Rad21/cohesin and inflammation/differentiation inducing signals in the resolution phase after acute inflammation. and The inhibition of cohesin/NF-κB is sufficient to revert the hypersensitivity of aged HSPCs to inflammation-induced differentiation. During aging, myeloid-biased HSCs with disrupted and naturally occurring reduced expression of Rad21/cohesin are increasingly selected over lymphoid-biased HSCs. Together, Rad21/cohesin mediated NF-κB signaling limits HSPC function during aging and selects for cohesin deficient HSCs with myeloid skewed differentiation.
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Project description:Collombet2016 - Lymphoid and myeloid cell
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This model is described in the article:
Logical modeling of lymphoid
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Proceedings of the National Academy of
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Abstract:
Blood cells are derived from a common set of hematopoietic
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lymphoid/myeloid cell-fate decisions.
This model is hosted on
BioModels Database
and identified by:
MODEL1610240000.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-06-08 | MODEL1610240000 | BioModels
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