An Engineered CRISPR-Cas9 Mouse Line for Simultaneous Readout of Lineage Histories and Gene Expression Profiles in Single Cells.
Cell
; 181(6): 1410-1422.e27, 2020 06 11.
Article
en En
| MEDLINE
| ID: mdl-32413320
ABSTRACT
Tracing the lineage history of cells is key to answering diverse and fundamental questions in biology. Coupling of cell ancestry information with other molecular readouts represents an important goal in the field. Here, we describe the CRISPR array repair lineage tracing (CARLIN) mouse line and corresponding analysis tools that can be used to simultaneously interrogate the lineage and transcriptomic information of single cells in vivo. This model exploits CRISPR technology to generate up to 44,000 transcribed barcodes in an inducible fashion at any point during development or adulthood, is compatible with sequential barcoding, and is fully genetically defined. We have used CARLIN to identify intrinsic biases in the activity of fetal liver hematopoietic stem cell (HSC) clones and to uncover a previously unappreciated clonal bottleneck in the response of HSCs to injury. CARLIN also allows the unbiased identification of transcriptional signatures associated with HSC activity without cell sorting.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linaje de la Célula
/
Transcriptoma
/
Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas
/
Sistemas CRISPR-Cas
Límite:
Animals
Idioma:
En
Revista:
Cell
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos