HUMAN HEMATOPOIETIC STEM CELL DIFFERENTIATION FOLLOWS A CONTINUOUS WADDINGTON-LIKE LANDSCAPE
(Abstract release date: 05/19/16)
EHA Library. Essers M. 06/10/16; 135174; S141
Dr. Marieke Essers
Contributions
Contributions
Abstract
Abstract: S141
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 11:30 - 11:45
Location: Room H5
Background
Blood formation is believed to occur via the step-wise progression of haematopoietic stem cells (HSCs) through a tree-like hierarchy of discrete progenitor cell types. Although several recent studies have challenged different aspects of this dogma, a comprehensive model of haematopoiesis and entry of HSCs into lineage commitment is currently lacking. Here, we mapped human bone marrow haematopoiesis by quantitatively integrating flow cytometric, transcriptomic and functional lineage fate data at the single-cell level.
Aims
Reconstruction of how individual HSCs enter lineage commitment by quantitatively integrating transcriptomic and functional single cell data that permits the reconstruction of developmental trajectories during HSC differentiation.
Methods
Healthy human BM HSPCs (Lin-CD34+) were individually sorted and surface marker fluorescence intensities of a panel of FACS surface markers commonly used to characterize these HSPCs were recorded to retrospectively reconstruct immunophenotypes. Index-sorted HSPCs were subjected to RNAseq (“index-omics”, 379 cells) to determine their transcriptomes or individually cultured ex vivo (“index-culture”, 1021 cells) to quantify lineage potential. Subsequently, the functional and transcriptomic data sets were integrated using commonly indexed surface marker expression to identify molecular and cellular events associated with the differentiation of human HSCs at the single cell level.
Results
We found that individual HSCs neither enter lineage commitment at binary branching points nor pass through discrete intermediate progenitor cell stages. In contrast, HSC lineage commitment occurs in a gradual manner best described by a continuous Waddington landscape with initially flat but progressively deepening valleys. Our data determine a detailed model of developmental trajectories within this landscape, as well as their underlying gene expression modules and biological processes.
Conclusion
Integration of transcriptomic and functional cell fate data at the single-cell level reveals that human hematopoiesis is not organized in a hierarchical “tree” of cell types, but follows a continuous differentiation flow within a Waddington-like landscape with initially flat and gradually deepening valleys.
Session topic: Stem cells and the microenvironment
Keyword(s): Bone Marrow, Differentiation, HSC, Transcriptional regulation
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 11:30 - 11:45
Location: Room H5
Background
Blood formation is believed to occur via the step-wise progression of haematopoietic stem cells (HSCs) through a tree-like hierarchy of discrete progenitor cell types. Although several recent studies have challenged different aspects of this dogma, a comprehensive model of haematopoiesis and entry of HSCs into lineage commitment is currently lacking. Here, we mapped human bone marrow haematopoiesis by quantitatively integrating flow cytometric, transcriptomic and functional lineage fate data at the single-cell level.
Aims
Reconstruction of how individual HSCs enter lineage commitment by quantitatively integrating transcriptomic and functional single cell data that permits the reconstruction of developmental trajectories during HSC differentiation.
Methods
Healthy human BM HSPCs (Lin-CD34+) were individually sorted and surface marker fluorescence intensities of a panel of FACS surface markers commonly used to characterize these HSPCs were recorded to retrospectively reconstruct immunophenotypes. Index-sorted HSPCs were subjected to RNAseq (“index-omics”, 379 cells) to determine their transcriptomes or individually cultured ex vivo (“index-culture”, 1021 cells) to quantify lineage potential. Subsequently, the functional and transcriptomic data sets were integrated using commonly indexed surface marker expression to identify molecular and cellular events associated with the differentiation of human HSCs at the single cell level.
Results
We found that individual HSCs neither enter lineage commitment at binary branching points nor pass through discrete intermediate progenitor cell stages. In contrast, HSC lineage commitment occurs in a gradual manner best described by a continuous Waddington landscape with initially flat but progressively deepening valleys. Our data determine a detailed model of developmental trajectories within this landscape, as well as their underlying gene expression modules and biological processes.
Conclusion
Integration of transcriptomic and functional cell fate data at the single-cell level reveals that human hematopoiesis is not organized in a hierarchical “tree” of cell types, but follows a continuous differentiation flow within a Waddington-like landscape with initially flat and gradually deepening valleys.
Session topic: Stem cells and the microenvironment
Keyword(s): Bone Marrow, Differentiation, HSC, Transcriptional regulation
Abstract: S141
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 11:30 - 11:45
Location: Room H5
Background
Blood formation is believed to occur via the step-wise progression of haematopoietic stem cells (HSCs) through a tree-like hierarchy of discrete progenitor cell types. Although several recent studies have challenged different aspects of this dogma, a comprehensive model of haematopoiesis and entry of HSCs into lineage commitment is currently lacking. Here, we mapped human bone marrow haematopoiesis by quantitatively integrating flow cytometric, transcriptomic and functional lineage fate data at the single-cell level.
Aims
Reconstruction of how individual HSCs enter lineage commitment by quantitatively integrating transcriptomic and functional single cell data that permits the reconstruction of developmental trajectories during HSC differentiation.
Methods
Healthy human BM HSPCs (Lin-CD34+) were individually sorted and surface marker fluorescence intensities of a panel of FACS surface markers commonly used to characterize these HSPCs were recorded to retrospectively reconstruct immunophenotypes. Index-sorted HSPCs were subjected to RNAseq (“index-omics”, 379 cells) to determine their transcriptomes or individually cultured ex vivo (“index-culture”, 1021 cells) to quantify lineage potential. Subsequently, the functional and transcriptomic data sets were integrated using commonly indexed surface marker expression to identify molecular and cellular events associated with the differentiation of human HSCs at the single cell level.
Results
We found that individual HSCs neither enter lineage commitment at binary branching points nor pass through discrete intermediate progenitor cell stages. In contrast, HSC lineage commitment occurs in a gradual manner best described by a continuous Waddington landscape with initially flat but progressively deepening valleys. Our data determine a detailed model of developmental trajectories within this landscape, as well as their underlying gene expression modules and biological processes.
Conclusion
Integration of transcriptomic and functional cell fate data at the single-cell level reveals that human hematopoiesis is not organized in a hierarchical “tree” of cell types, but follows a continuous differentiation flow within a Waddington-like landscape with initially flat and gradually deepening valleys.
Session topic: Stem cells and the microenvironment
Keyword(s): Bone Marrow, Differentiation, HSC, Transcriptional regulation
Type: Oral Presentation
Presentation during EHA21: On Friday, June 10, 2016 from 11:30 - 11:45
Location: Room H5
Background
Blood formation is believed to occur via the step-wise progression of haematopoietic stem cells (HSCs) through a tree-like hierarchy of discrete progenitor cell types. Although several recent studies have challenged different aspects of this dogma, a comprehensive model of haematopoiesis and entry of HSCs into lineage commitment is currently lacking. Here, we mapped human bone marrow haematopoiesis by quantitatively integrating flow cytometric, transcriptomic and functional lineage fate data at the single-cell level.
Aims
Reconstruction of how individual HSCs enter lineage commitment by quantitatively integrating transcriptomic and functional single cell data that permits the reconstruction of developmental trajectories during HSC differentiation.
Methods
Healthy human BM HSPCs (Lin-CD34+) were individually sorted and surface marker fluorescence intensities of a panel of FACS surface markers commonly used to characterize these HSPCs were recorded to retrospectively reconstruct immunophenotypes. Index-sorted HSPCs were subjected to RNAseq (“index-omics”, 379 cells) to determine their transcriptomes or individually cultured ex vivo (“index-culture”, 1021 cells) to quantify lineage potential. Subsequently, the functional and transcriptomic data sets were integrated using commonly indexed surface marker expression to identify molecular and cellular events associated with the differentiation of human HSCs at the single cell level.
Results
We found that individual HSCs neither enter lineage commitment at binary branching points nor pass through discrete intermediate progenitor cell stages. In contrast, HSC lineage commitment occurs in a gradual manner best described by a continuous Waddington landscape with initially flat but progressively deepening valleys. Our data determine a detailed model of developmental trajectories within this landscape, as well as their underlying gene expression modules and biological processes.
Conclusion
Integration of transcriptomic and functional cell fate data at the single-cell level reveals that human hematopoiesis is not organized in a hierarchical “tree” of cell types, but follows a continuous differentiation flow within a Waddington-like landscape with initially flat and gradually deepening valleys.
Session topic: Stem cells and the microenvironment
Keyword(s): Bone Marrow, Differentiation, HSC, Transcriptional regulation
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