Nature: Single-cell lineage tracking has found important functions of TCF5 in hematopoietic action.

A bone marrow transplant is the treatment of a patient's blood and immune system by entering a haematopoietic stem cell (haematopoietic stem cells, HSCs) to treat a disease such as leukemia or immunodeficiency. the success rate of
bone marrow transplant depends greatly on the regenerative capacity of hematopoietic stem cells.
hematopoietic stem cells have a strong heterogeneity, the regeneration capacity of each clone is very different, but the current regulatory mechanism is not clear.
the rapid development of single-cell sequencing techniques in recent years reveals the differences in HSCs transcription groups and provides a possible direction for understanding the heterogeneity of their function.
however, single-cell sequencing is destructive and difficult to observe the state and function of HSCs at the same time.
to address this issue, in April, Allon M. from Harvard Medical School. Professor Klein published a new technique in Science that can simultaneously map cell states and transcription groups, first building a DNA barcode library (lineage and RNA, LARRY, sequence random 28bp fragments) and using slow-virus transfection to insert inheritable DNA barcodes into the HSCs genome, where individual cell sequencing can tell the differences between early and late detection of cloned clones, linking cell fate decisions to early transcription groups (see BioArt).
recently, Professor Fernando D. Camargo from Harvard University, in collaboration with Professor Allon M. Klein, published a study in Nature, "Single-cell lineage tracing unveils a row for TCF15 in haemapois", using the DNA barcode library to reveal the intrinsic molecular characteristics of HSCs with different regenerative capabilities, and identified the importance of transcription factor TCF5 to maintain hCs.
the researchers first isolated long-term hematopoietic stem cells (long-term HSCs) from mice and re-injected them into mice after transfection of DNA barcodes. After 4 months of
, the bone marrow of the mice was taken for flow sorting and single-cell sequencing.
, the researchers found that the self-renewal and differentiation ability of HSCs can be divided into the low output group and the high output group, and the two groups of cells between the transcription group gap is large, indicating that HSCs self-renewal ability is maintained by the inherent genetic characteristics.
after two bone marrow transplants, the mice kept the low output cells, while the cells of the high output group largely disappeared.
to further identify genes that promote the regenerative ability of HSCs, the researchers used CRISPR to activate 63 genes that were expressed highly in the low output group and were not reported to participate in HSCs' ability to self-renew.
, transcription factor TCF5 exhibits very specific characteristics of high expression in the low output group, and the activation of TCF5 can further increase the proportion of cells in the low output group, indicating that TCF5 promotes the regeneration of HSCs.
in general, the study found the molecular mechanism that regulates the regenerative ability of HSCs, and identified TCF5 as a transcription factor that could promote the success rate of bone marrow transplantation, which has important clinical significance.
, the method can also be applied to the study of other tissues with regenerative capabilities.
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