Lineage tracing on transcriptional landscapes links state to fate during differentiation
Harvard University · Center for Systems Biology · +1 more institution
Abstract
A challenge in biology is to associate molecular differences among progenitor cells with their capacity to generate mature cell types. Here, we used expressed DNA barcodes to clonally trace transcriptomes over time and applied this to study fate determination in hematopoiesis. We identified states of primed fate potential and located them on a continuous transcriptional landscape. We identified two routes of monocyte differentiation that leave an imprint on mature cells. Analysis of sister cells also revealed cells to have intrinsic fate biases not detectable by single-cell RNA sequencing. Finally, we benchmarked computational methods of dynamic inference from single-cell snapshots, showing that fate choice…
Citation impact
- FWCI
- 34.92
- Percentile
- 100%
- References
- 36
Authors
4- CWCaleb WeinrebCorresponding
Harvard University, Center for Systems Biology
- ARAlejo Rodriguez-FraticelliCorresponding
Boston Children's Hospital, Harvard University
- FDFernando D. CamargoCorresponding
Boston Children's Hospital, Harvard University
- AMAllon M. KleinCorresponding
Harvard University, Center for Systems Biology
Topics & keywords
- Biology
- Cell fate determination
- Cellular differentiation
- Embryonic stem cell
- Haematopoiesis
- Stem cell
- Progenitor cell
- Gene
Funding
- ASAmerican Society of HematologyAward: 3391-19
- CZChan Zuckerberg InitiativeAward: 2018-182714
- EEMBOAward: ALTF 675-2015
- NINational Institutes of HealthAward: K99HL146983
- HSHarvard Stem Cell InstituteAward: DP-0174-18-00
- NONIH Office of the DirectorAwards: P01HL13147, R33CA212697-01, HL128850-01A1, 1R01HL14102-01