| Download | - View final version: External signals regulate continuous transcriptional states in hematopoietic stem cells (PDF, 3.9 MiB)
- View supplementary information: External signals regulate continuous transcriptional states in hematopoietic stem cells (PDF, 7.7 MiB)
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| DOI | Resolve DOI: https://doi.org/10.7554/eLife.66512 |
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| Author | Search for: Fast, Eva M.ORCID identifier: https://orcid.org/0000-0002-4261-5244; Search for: Sporrij, Audrey; Search for: Manning, Margot; Search for: Rocha, Edroaldo Lummertz; Search for: Yang, Song; Search for: Zhou, Yi; Search for: Guo, Jimin1; Search for: Baryawno, Ninib; Search for: Barkas, Nikolaos; Search for: Scadden, David; Search for: Camargo, Fernando; Search for: Zon, Leonard I.ORCID identifier: https://orcid.org/0000-0003-0860-926X |
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| Affiliation | - National Research Council of Canada. Medical Devices
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| Funder | Search for: National Institutes of Health; Search for: Leukemia and Lymphoma Society; Search for: Boehringer Ingelheim Fonds |
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| Format | Text, Article |
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| Abstract | 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. |
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| Publication date | 2021-12-23 |
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| Publisher | eLife Sciences Publications |
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| Licence | |
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| Language | English |
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| Peer reviewed | Yes |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | f220d802-7451-46b6-9bfa-180f4f13394d |
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| Record created | 2023-07-12 |
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| Record modified | 2023-07-12 |
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