Hematopoietic Reprogramming In Vitro Informs In Vivo Identification of Hemogenic Precursors to Definitive Hematopoietic Stem Cells
(2016) In Developmental Cell 36(5). p.525-539- Abstract
Definitive hematopoiesis emerges via an endothelial-to-hematopoietic transition in the embryo and placenta; however, the precursor cells to hemogenic endothelium are not defined phenotypically. We previously demonstrated that the induction of hematopoietic progenitors from fibroblasts progresses through hemogenic precursors that are Prom1+Sca1+CD34+CD45- (PS34CD45-). Guided by these studies, we analyzed mouse placentas and identified a population with this phenotype. These cells express endothelial markers, are heterogeneous for early hematopoietic markers, and localize to the vascular labyrinth. Remarkably, global gene expression profiles of PS34CD45- cells correlate... (More)
Definitive hematopoiesis emerges via an endothelial-to-hematopoietic transition in the embryo and placenta; however, the precursor cells to hemogenic endothelium are not defined phenotypically. We previously demonstrated that the induction of hematopoietic progenitors from fibroblasts progresses through hemogenic precursors that are Prom1+Sca1+CD34+CD45- (PS34CD45-). Guided by these studies, we analyzed mouse placentas and identified a population with this phenotype. These cells express endothelial markers, are heterogeneous for early hematopoietic markers, and localize to the vascular labyrinth. Remarkably, global gene expression profiles of PS34CD45- cells correlate with reprogrammed precursors and establish a hemogenic precursor cell molecular signature. PS34CD45- cells are also present in intra-embryonic hemogenic sites. After stromal co-culture, PS34CD45- cells give rise to all blood lineages and engraft primary and secondary immunodeficient mice. In summary, we show that reprogramming reveals a phenotype for in vivo precursors to hemogenic endothelium, establishing that direct in vitro conversion informs developmental processes in vivo.
(Less)
- author
- publishing date
- 2016-03-07
- type
- Contribution to journal
- publication status
- published
- in
- Developmental Cell
- volume
- 36
- issue
- 5
- pages
- 15 pages
- publisher
- Cell Press
- external identifiers
-
- scopus:84959312876
- pmid:26954547
- ISSN
- 1534-5807
- DOI
- 10.1016/j.devcel.2016.02.011
- language
- English
- LU publication?
- no
- id
- bd8f8f62-7666-4bc6-b82c-6ebaf373e8da
- date added to LUP
- 2017-10-02 17:25:25
- date last changed
- 2024-04-14 18:43:20
@article{bd8f8f62-7666-4bc6-b82c-6ebaf373e8da, abstract = {{<p>Definitive hematopoiesis emerges via an endothelial-to-hematopoietic transition in the embryo and placenta; however, the precursor cells to hemogenic endothelium are not defined phenotypically. We previously demonstrated that the induction of hematopoietic progenitors from fibroblasts progresses through hemogenic precursors that are Prom1<sup>+</sup>Sca1<sup>+</sup>CD34<sup>+</sup>CD45<sup>-</sup> (PS34CD45<sup>-</sup>). Guided by these studies, we analyzed mouse placentas and identified a population with this phenotype. These cells express endothelial markers, are heterogeneous for early hematopoietic markers, and localize to the vascular labyrinth. Remarkably, global gene expression profiles of PS34CD45<sup>-</sup> cells correlate with reprogrammed precursors and establish a hemogenic precursor cell molecular signature. PS34CD45<sup>-</sup> cells are also present in intra-embryonic hemogenic sites. After stromal co-culture, PS34CD45<sup>-</sup> cells give rise to all blood lineages and engraft primary and secondary immunodeficient mice. In summary, we show that reprogramming reveals a phenotype for in vivo precursors to hemogenic endothelium, establishing that direct in vitro conversion informs developmental processes in vivo.</p>}}, author = {{Pereira, Carlos Filipe and Chang, Betty and Gomes, Andreia and Bernitz, Jeffrey M. and Papatsenko, Dmitri and Niu, Xiaohong and Swiers, Gemma and Azzoni, Emanuele and de Bruijn, Marella F T R and Schaniel, Christoph and Lemischka, Ihor R. and Moore, Kateri A.}}, issn = {{1534-5807}}, language = {{eng}}, month = {{03}}, number = {{5}}, pages = {{525--539}}, publisher = {{Cell Press}}, series = {{Developmental Cell}}, title = {{Hematopoietic Reprogramming In Vitro Informs In Vivo Identification of Hemogenic Precursors to Definitive Hematopoietic Stem Cells}}, url = {{http://dx.doi.org/10.1016/j.devcel.2016.02.011}}, doi = {{10.1016/j.devcel.2016.02.011}}, volume = {{36}}, year = {{2016}}, }