scholarly journals Lineage tracing of murine adult hematopoietic stem cells reveals active contribution to steady-state hematopoiesis

2018 ◽  
Vol 2 (11) ◽  
pp. 1220-1228 ◽  
Author(s):  
Richard H. Chapple ◽  
Yu-Jung Tseng ◽  
Tianyuan Hu ◽  
Ayumi Kitano ◽  
Makiko Takeichi ◽  
...  

Key Points HSCs contribute robustly to steady-state hematopoiesis. Platelets receive extensive influx from HSCs compared with other myeloid or lymphoid cells.

Blood ◽  
2016 ◽  
Vol 128 (19) ◽  
pp. 2307-2318 ◽  
Author(s):  
Bilal N. Sheikh ◽  
Yuqing Yang ◽  
Jaring Schreuder ◽  
Susan K. Nilsson ◽  
Rebecca Bilardi ◽  
...  

Key Points MOZ deletion in adult mice leads to a rapid loss of cells with HSC cell surface immuno-phenotype and transplantation ability. Absence of classically defined HSCs for an extended period does not substantially affect steady-state hematopoiesis.


2018 ◽  
Author(s):  
Petter Säwén ◽  
Mohamed Eldeeb ◽  
Eva Erlandsson ◽  
Trine A Kristiansen ◽  
Cecilia Laterza ◽  
...  

ABSTRACTA hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. It is well established that adult hematopoietic stem cells (HSCs) are active contributors to these processes after transplantation, yet their role in native hematopoiesis has recently been called into question. Here, we use inducible lineage tracing from genetically marked adult HSCs to explore their roles in the steady state. We show that adult HSCs contribute robustly to all lineages via intermediate progenitor cells, but with neglible production of hematopoietic cells with a known fetal origin. We further reveal that the timing for regeneration of distinct blood lineages varies substantially. Finally, HSC contribution to multilineage hematopoiesis in aged animals declines with increasing age. Therefore, while HSCs are active contributors to native adult hematopoiesis, it appears that the numerical increase of HSCs is a physiologically relevant compensatory mechanism to account for a reduced differentiation capacity with age.


Blood ◽  
2013 ◽  
Vol 121 (12) ◽  
pp. 2234-2243 ◽  
Author(s):  
Yong-Oon Ahn ◽  
Bruce R. Blazar ◽  
Jeffrey S. Miller ◽  
Michael R. Verneris

Key Points ILC22 and cNK cells can be distinguished on the basis of LFA-1 expression. ILC22 and cNK cells have differing requirements for their development from hematopoietic stem cells.


2013 ◽  
Vol 11 (1) ◽  
pp. 625-633 ◽  
Author(s):  
Philippe Brunet de la Grange ◽  
Marija Vlaski ◽  
Pascale Duchez ◽  
Jean Chevaleyre ◽  
Veronique Lapostolle ◽  
...  

2011 ◽  
Vol 11 ◽  
pp. 1068-1076 ◽  
Author(s):  
Gero Hütter ◽  
Susanne Ganepola

Today, 30 years after the onset of the HIV pandemic, although treatment strategies have considerably improved, there is still no cure for the disease. Recently, we described a successful hematopoietic stem cell transplantation in an HIV-1–infected patient, transferring donor-derived cells with a natural resistance against HIV infection. These hematopoietic stem cells engrafted, proliferated, and differentiated into mature myeloid and lymphoid cells. To date, the patient has not required any antiretroviral treatment, more than 4 years after allogeneic transplantation. In the analysis of peripheral blood cells and different tissue samples, including gut, liver, and brain, no viral load or proviral DNA could be detected. Our report raises the hope for further targeted treatment strategies against HIV and represents a successful personalized treatment with allogeneic stem cells carrying a beneficial gene. However, this case has ignited a controversy regarding the question of whether this patient has achieved complete eradication of HIV or not. Here we give an update on open questions, unsolved aspects, and clinical consequences concerning this unique case.


Author(s):  
Wanbo Tang ◽  
Jian He ◽  
Tao Huang ◽  
Zhijie Bai ◽  
Chaojie Wang ◽  
...  

In the aorta-gonad-mesonephros (AGM) region of mouse embryos, pre-hematopoietic stem cells (pre-HSCs) are generated from rare and specialized hemogenic endothelial cells (HECs) via endothelial-to-hematopoietic transition, followed by maturation into bona fide hematopoietic stem cells (HSCs). As HECs also generate a lot of hematopoietic progenitors not fated to HSCs, powerful tools that are pre-HSC/HSC-specific become urgently critical. Here, using the gene knockin strategy, we firstly developed an Hlf-tdTomato reporter mouse model and detected Hlf-tdTomato expression exclusively in the hematopoietic cells including part of the immunophenotypic CD45– and CD45+ pre-HSCs in the embryonic day (E) 10.5 AGM region. By in vitro co-culture together with long-term transplantation assay stringent for HSC precursor identification, we further revealed that unlike the CD45– counterpart in which both Hlf-tdTomato-positive and negative sub-populations harbored HSC competence, the CD45+ E10.5 pre-HSCs existed exclusively in Hlf-tdTomato-positive cells. The result indicates that the cells should gain the expression of Hlf prior to or together with CD45 to give rise to functional HSCs. Furthermore, we constructed a novel Hlf-CreER mouse model and performed time-restricted genetic lineage tracing by a single dose induction at E9.5. We observed the labeling in E11.5 AGM precursors and their contribution to the immunophenotypic HSCs in fetal liver (FL). Importantly, these Hlf-labeled early cells contributed to and retained the size of the HSC pool in the bone marrow (BM), which continuously differentiated to maintain a balanced and long-term multi-lineage hematopoiesis in the adult. Therefore, we provided another valuable mouse model to specifically trace the fate of emerging HSCs during development.


2021 ◽  
Author(s):  
Bianca A Ulloa ◽  
Samima S Habbsa ◽  
Kathryn S Potts ◽  
Alana Lewis ◽  
Mia McKinstry ◽  
...  

Hematopoietic stem cells (HSCs) are rare cells that arise in the embryo and sustain adult hematopoiesis. Although the functional potential of nascent HSCs is detectable by transplantation, their native contribution during development is unknown, in part due to the overlapping genesis and marker gene expression with other embryonic blood progenitors. Using single cell transcriptomics, we defined gene signatures that distinguish nascent HSCs from embryonic blood progenitors. Applying a new lineage tracing approach, we selectively tracked HSC output in situ and discovered significantly delayed lymphomyeloid contribution. Using a novel inducible HSC injury model, we demonstrated a negligible impact on larval lymphomyelopoiesis following HSC depletion. HSCs are not merely dormant at this developmental stage as they showed robust regeneration after injury. Combined, our findings illuminate that nascent HSCs self-renew but display differentiation latency, while HSC-independent embryonic progenitors sustain developmental hematopoiesis. Understanding the differences among embryonic HSC and progenitor populations will guide improved de novo generation and expansion of functional HSCs.


2021 ◽  
Author(s):  
Xu Fan ◽  
Pei Lu ◽  
Xianghua Cui ◽  
Peng Wu ◽  
Weiran Lin ◽  
...  

Abstract Kupffer cells (KCs) originate from yolk sac progenitors before birth, but the origin of repopulating KCs in adult remains unclear. In current study, we firstly traced the fate of preexisting KCs and that of monocytic cells with tissue-resident macrophage-specific and monocytic cell-specific fate mapping mouse models, respectively, and found no evidences that repopulating KCs originate from preexisting KCs or MOs. Secondly, we performed genetic lineage tracing to determine the type of progenitor cells involved in response to KC depletion in mice, and found that in response to KC depletion, hematopoietic stem cells (HSCs) proliferated in the bone marrow, mobilized into the blood, adoptively transferred into the liver and differentiated into KCs. Finally, we traced the fate of HSCs in a HSC-specific fate-mapping mouse model, in context of chronic liver inflammation induced by repeated carbon tetrachloride treatment, and confirmed that repopulating KCs originated directly from HSCs. Taken together, these findings provided in vivo fate-mapping evidences that repopulating KCs originate directly from hematopoietic stem cells, which present a completely novel understanding of the cellular origin of repopulating Kupffer Cells and shedding light on the divergent roles of KCs in liver homeostasis and diseases.


Blood ◽  
2013 ◽  
Vol 122 (10) ◽  
pp. 1730-1740 ◽  
Author(s):  
Francois Lassailly ◽  
Katie Foster ◽  
Lourdes Lopez-Onieva ◽  
Erin Currie ◽  
Dominique Bonnet

Key Points Comparative analysis of epiphyses, diaphyses, and calvaria in terms of homeostatic HSC content, homing, and early reconstitution is described. Noninvasive intravital imaging of intact bones and assessment of BVF, BRA, and hypoxia are reported.


Blood ◽  
2014 ◽  
Vol 124 (10) ◽  
pp. 1622-1625 ◽  
Author(s):  
Serine Avagyan ◽  
Michael Churchill ◽  
Kenta Yamamoto ◽  
Jennifer L. Crowe ◽  
Chen Li ◽  
...  

Key Points XLF-deficient mice recapitulate the lymphocytopenia of XLF-deficient patients. Premature aging of hematopoietic stem cells underlies the severe and progressive lymphocytopenia in XLF-deficient mice.


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