External signals regulate continuous transcriptional states in hematopoietic stem cells.

Autor:	Fast EM; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States., Sporrij A; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States., Manning M; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States., Rocha EL; Laboratório de Imunobiologia, Departmento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Florianópolis, Brazil., Yang S; Stem Cell Program and Division of Hematology/Oncology, Howard Hughes Medical Institute, Boston's Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, United States., Zhou Y; Stem Cell Program and Division of Hematology/Oncology, Howard Hughes Medical Institute, Boston's Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, United States., Guo J; Medical Devices Research Centre, National Research Council Canada, Boucherville, Canada., Baryawno N; Childhood Cancer Research Unit, Department of Children's and Women's Health, Karolinska Institutet, Stockholm, Sweden., Barkas N; Broad Institute of Harvard and MIT, Cambridge, United States., Scadden D; Harvard University, Cambridge, United States., Camargo F; Children's Hospital Harvard Med Sch, Cambridge, United States., Zon LI; Stem Cell Program and Hematology/Oncology, Boston Children's Hospital, Boston, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 Dec 23; Vol. 10. Date of Electronic Publication: 2021 Dec 23.
DOI:	10.7554/eLife.66512
Abstrakt:	Hematopoietic stem cells (HSCs) must ensure adequate blood cell production following distinct external stressors. A comprehensive understanding of in vivo heterogeneity and specificity of HSC responses to external stimuli is currently lacking. We performed single-cell RNA sequencing (scRNA-Seq) on functionally validated mouse HSCs and LSK (Lin-, c-Kit+, Sca1+) progenitors after in vivo pharmacological perturbation of niche signals interferon, granulocyte colony-stimulating factor (G-CSF), and prostaglandin. We identified six HSC states that are characterized by enrichment but not exclusive expression of marker genes. External signals induced rapid transitions between HSC states but transcriptional response varied both between external stimulants and within the HSC population for a given perturbation. In contrast to LSK progenitors, HSCs were characterized by a greater link between molecular signatures at baseline and in response to external stressors. Chromatin analysis of unperturbed HSCs and LSKs by scATAC-Seq suggested some HSC-specific, cell intrinsic predispositions to niche signals. We compiled a comprehensive resource of HSC- and LSK progenitor-specific chromatin and transcriptional features that represent determinants of signal receptiveness and regenerative potential during stress hematopoiesis. Competing Interests: EF, AS, MM, ER, SY, YZ, JG, NB, NB, FC No competing interests declared, DS is a director and equity holder of Agios Pharmaceuticals, Magenta Therapeutics, Editas Medicines, ClearCreekBio, and Life-VaultBio; a founder of Fate Therapeutics and Magenta Therapeutics; and a consultant to FOG Pharma and VCanBio, LZ is founder and stockholder of Fate, Inc, Scholar Rock, Camp4 therapeutics and a scientific advisor for Stemgent (© 2021, Fast et al.)
Databáze:	MEDLINE
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