Abstract
Appropriate hematopoietic stem cell (HSC) self-renewal reflects the tight regulation of cell cycle entry and lineage commitment. Here, we show that Id1, a dominant-negative regulator of E protein transcription factors, maintains HSC self-renewal by preserving the undifferentiated state. Id1-deficient HSCs show increased cell cycling, by BrdU incorporation in vivo, but fail to efficiently self-renew, leading to low steady-state HSC numbers and premature exhaustion in serial bone marrow transplant assays. The increased cycling reflects the perturbed differentiation process, because Id1 null HSCs more readily commit to myeloid differentiation, with inappropriate expression of myeloerythroid- specific genes. Thus, Id1 appears to regulate the fate of HSCs by acting as a true inhibitor of differentiation.
| Original language | English |
|---|---|
| Pages (from-to) | 1260-1265 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 104 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Jan 23 2007 |
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Keywords
- Cell fate determination
- Differentiation
- Transcriptional regulation
ASJC Scopus subject areas
- Genetics
- General
Cite this
Id1 restrains myeloid commitment, maintaining the self-renewal capacity of hematopoietic stem cells. / Jankovic, Vladimir; Ciarrocchi, Alessia; Boccuni, Piernicola; DeBlasio, Tony; Benezra, Robert; Nimer, Stephen D.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 4, 23.01.2007, p. 1260-1265.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Id1 restrains myeloid commitment, maintaining the self-renewal capacity of hematopoietic stem cells
AU - Jankovic, Vladimir
AU - Ciarrocchi, Alessia
AU - Boccuni, Piernicola
AU - DeBlasio, Tony
AU - Benezra, Robert
AU - Nimer, Stephen D.
PY - 2007/1/23
Y1 - 2007/1/23
N2 - Appropriate hematopoietic stem cell (HSC) self-renewal reflects the tight regulation of cell cycle entry and lineage commitment. Here, we show that Id1, a dominant-negative regulator of E protein transcription factors, maintains HSC self-renewal by preserving the undifferentiated state. Id1-deficient HSCs show increased cell cycling, by BrdU incorporation in vivo, but fail to efficiently self-renew, leading to low steady-state HSC numbers and premature exhaustion in serial bone marrow transplant assays. The increased cycling reflects the perturbed differentiation process, because Id1 null HSCs more readily commit to myeloid differentiation, with inappropriate expression of myeloerythroid- specific genes. Thus, Id1 appears to regulate the fate of HSCs by acting as a true inhibitor of differentiation.
AB - Appropriate hematopoietic stem cell (HSC) self-renewal reflects the tight regulation of cell cycle entry and lineage commitment. Here, we show that Id1, a dominant-negative regulator of E protein transcription factors, maintains HSC self-renewal by preserving the undifferentiated state. Id1-deficient HSCs show increased cell cycling, by BrdU incorporation in vivo, but fail to efficiently self-renew, leading to low steady-state HSC numbers and premature exhaustion in serial bone marrow transplant assays. The increased cycling reflects the perturbed differentiation process, because Id1 null HSCs more readily commit to myeloid differentiation, with inappropriate expression of myeloerythroid- specific genes. Thus, Id1 appears to regulate the fate of HSCs by acting as a true inhibitor of differentiation.
KW - Cell fate determination
KW - Differentiation
KW - Transcriptional regulation
UR - http://www.scopus.com/inward/record.url?scp=33846626042&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846626042&partnerID=8YFLogxK
U2 - 10.1073/pnas.0607894104
DO - 10.1073/pnas.0607894104
M3 - Article
C2 - 17227850
AN - SCOPUS:33846626042
VL - 104
SP - 1260
EP - 1265
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 4
ER -